What has Steere said in published articles regarding Lyme disease?
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                                                      as of 2 March 2000

In collaboration with others, not primary author:

108 citations, 12 have "NO ABSTRACT AVAILABLE."

TITLE: 
Prominent expression of mRNA for proinflammatory
cytokines in synovium in patients with juvenile rheumatoid
arthritis or chronic Lyme arthritis [In Process Citation]
AUTHORS: 
Harjacek M; Diaz-Cano S; Alman BA; Coburn J; Ruthazer
R; Wolfe H; Steere AC
AUTHOR
AFFILIATION: 
Department of Medicine, New England Medical Center,
Tufts University School of Medicine, Boston, MA 02111,
USA.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS 
SOURCE: 
J Rheumatol 2000 Feb;27(2):497-503
[MEDLINE record in process]
ABSTRACT: 
OBJECTIVE: To examine the cytokine profiles in synovium
of patients with juvenile rheumatoid arthritis (JRA) or Lyme
arthritis, 2 chronic inflammatory arthritides that affect
children. METHODS: We used in situ hybridization with
specific riboprobes to determine the expression of mRNA for
proinflammatory or antiinflammatory cytokines in synovial
samples from 5 patients with early, untreated JRA, 15
patients with late, treated JRA, and 9 patients with chronic
Lyme arthritis. For comparison, synovia were examined from
6 patients with rheumatoid or psoriatic arthritis, and from 9
patients with various orthopedic conditions. RESULTS:
Among the children with early, untreated JRA, a median of 3
to 8% of inflammatory cells in synovial samples expressed
mRNA for the proinflammatory cytokines interleukin 1beta
(IL-1beta), tumor necrosis factor-alpha(TNF-alpha), or
interferon-gamma (IFN- gamma). Although a median of 3.9%
of the cells expressed mRNA for the antiinflammatory
cytokine IL-10, none had IL-4 mRNA. Most of the patients
with late, treated JRA, chronic Lyme arthritis, rheumatoid, or
psoriatic arthritis had mRNA for each of these
proinflammatory cytokines in about 1% of the cells, whereas
mRNA for the antiinflammatory cytokines was less frequent.
The inflammatory cell density was much less in the synovium
of patients with various orthopedic conditions, but about 1%
of the infiltrating cells expressed mRNA for at least one of
the proinflammatory cytokines. CONCLUSION: Patients
with early or late JRA or chronic Lyme arthritis have
expression of mRNA in synovial tissue primarily for
proinflammatory cytokines, with less expression of
antiinflammatory cytokines.
CITATION IDS: PMID: 10685820 UI: 20148256
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=10685820&form=6&db=m&Dopt=b

TITLE: 
Lack of Borrelia burgdorferi DNA in synovial samples from
patients with antibiotic treatment-resistant Lyme arthritis.
AUTHORS: 
Carlson D; Hernandez J; Bloom BJ; Coburn J; Aversa JM;
Steere AC
AUTHOR
AFFILIATION: 
Tufts University School of Medicine, New England Medical
Center, Tupper Research Institute, Boston, Massachusetts
02111, USA.
GRANT/CONTRACT ID: 
AR-20358/AR/NIAMS
AR-07570/AR/NIAMS 
SOURCE: 
Arthritis Rheum 1999 Dec;42(12):2705-9
ABSTRACT: 
OBJECTIVE: To determine whether Borrelia burgdorferi
DNA may be detected in synovial tissue from patients with
Lyme arthritis who have persistent synovial inflammation
after antibiotic treatment. METHODS: Synovial specimens
obtained at synovectomy from 26 patients with antibiotic
treatment-resistant Lyme arthritis and from 10 control
subjects were tested for B burgdorferi DNA using 3
primer-probe sets that target genes encoding outer surface
proteins A or B or a flagellar protein (P41) of the spirochete.
RESULTS: The 26 patients with Lyme arthritis, who had
received antibiotic therapy for a mean total duration of 8
weeks prior to synovectomy, and the 10 control subjects
each had negative polymerase chain reaction (PCR) results
in synovial samples. When the samples were spiked with
approximately 1-10 B burgdorferi, all but 1 had positive PCR
results, suggesting that spirochetal DNA could have been
detected in most of the unspiked samples if it had been
present. CONCLUSION: These results indicate that
synovial inflammation may persist in some patients with
Lyme arthritis after the apparent eradication of the
spirochete from the joint with antibiotic therapy.
CITATION IDS: PMID: 10616021 UI: 20081767
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=10616021&form=6&db=m&Dopt=b

TITLE: 
Increased IgA rheumatoid factor and V(H)1 associated cross reactive 
idiotype expression in patients with Lyme arthritis and 
neuroborreliosis.
AUTHORS: 
Axford JS; Rees DH; Mageed RA; Wordsworth P; Alavi A; Steere AC
AUTHOR
AFFILIATION: 
Academic Unit for Musculoskeletal Disease, St George's Hospital
Medical School, London.
SOURCE: 
Ann Rheum Dis 1999 Dec;58(12):757-61
ABSTRACT: 
OBJECTIVE: To investigate whether autoreactive mechanisms
occur in Lyme disease (LD) by determining IgA, IgG and IgM
rheumatoid factor (RF) concentrations and RF associated cross
reactive idiotype (CRI) expression in the serum of LD patients,
with comparison to patients with rheumatoid arthritis (RA).
METHODS: The RF isotype profiles were determined in 59
patients with LD; erythema migrans (EM) (n=19), neuroborreliosis
(NB) (n=20) and Lyme arthritis (LA) (n=20). Mouse monoclonal
antibodies (mAbs) G6 and G8 (V(H)1 gene associated), D12
(V(H)3 gene associated) and C7 (V(kappa)III gene associated)
were then used to determine the RF associated CRI expression on
IgM antibodies in 16 of these LD patients (eight seropositive for
RF); (EM (n=3), NB (n=6), LA (n=7)). RESULTS: Seven (18%)
patients with either NB or LA had increased concentrations of IgA
RF compared with none with EM. Significant differences in the
number of patients with raised concentrations of IgG RF or IgM
RF were not found between the LD patient groups. Five (3NB,
1LA and 1 EM) (31%) and three (2NB and 1LA) (19%) of LD
patients had raised concentrations of the CRIs recognised by
mAbs G6 and G8, respectively. These CRIs were detected in LD
sera both with and without raised concentrations of RF and were
not demonstrated on anti-Borrelia burgdorferi antibodies using
ELISA. No LD sera tested had raised concentrations of the
determinants recognised by mAbs C7 or D12. CONCLUSION:
Significantly raised concentrations of IgA RF and increased use of
V(H)1 germline gene associated CRIs are found on IgM
antibodies in the serum of LD patients. These data indicate the
recruitment of autoreactive B lymphocytes in some patients with
the later stages of LD.
CITATION IDS: PMID: 10577962 UI: 20046954
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=10577962&form=6&db=m&Dopt=b

TITLE: 
Neuropsychological deficits in Lyme disease patients with
and without other evidence of central nervous system
pathology.
AUTHORS: 
Kaplan RF; Jones-Woodward L; Workman K; Steere AC;
Logigian EL; Meadows ME
AUTHOR
AFFILIATION: 
Department of Neurology, Tufts University School of
Medicine, Boston, Massachusetts, USA.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS 
SOURCE: 
Appl Neuropsychol 1999;6(1):3-11
ABSTRACT: 
A small percentage of Lyme patients develop mild to
moderate encephalopathic symptoms months to years after
diagnosis and treatment. Their symptoms typically include
fatigue, memory loss, sleep disturbance, and depression.
However, the etiology of this syndrome remains
controversial. It is generally thought that Lyme patients with
abnormal cerebral spinal fluid (CSF) have a neurological
basis to their illness. To further examine this question, we
compared Lyme patients with evidence of abnormal CSF,
intrathecal antibody to Borrelia burgdorferi, elevated
protein, or a positive polymerase chain reaction for B.
burgdorferi DNA (n = 14); Lyme patients with normal CSF (n
= 18); and healthy controls (n = 15) on a battery of
neuropsychological and personality tests. Although both
Lyme groups reported memory problems, only the Lyme
group with abnormal CSF had measurable memory deficits.
Both Lyme groups had higher depression scores than the
normal control group, although depression was not correlated
with memory scores. It appears that Lyme patients with
abnormal CSF may have a neurological basis to their illness,
whereas affective symptoms, common to many chronic
disorders, may predispose other Lyme patients to the
perception of cognitive dysfunction.
CITATION IDS: PMID: 10382565 UI: 99311574
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=10382565&form=6&db=m&Dopt=b

TITLE: 
Human antibody responses to VlsE antigenic variation
protein of Borrelia burgdorferi.
AUTHORS: 
Lawrenz MB; Hardham JM; Owens RT; Nowakowski J;
Steere AC; Wormser GP; Norris SJ
AUTHOR
AFFILIATION: 
Departments of Pathology and Laboratory Medicine and
Microbiology and Molecular Genetics, University of Texas
Medical School at Houston, Houston, Texas 77030, USA.
GRANT/CONTRACT ID: AI37277/AI/NIAID 
SOURCE: 
J Clin Microbiol 1999 Dec;37(12):3997-4004
ABSTRACT: 
VlsE is a 35-kDa surface-exposed lipoprotein of Borrelia
burgdorferi that was shown previously to undergo antigenic
variation through segmental recombination of silent vls
cassettes with vlsE during experimental mouse infections.
Previous data had indicated that sera from North American
Lyme disease patients and experimentally infected animals
contained antibodies reactive with VlsE. In this study, sera
from patients with Lyme disease, syphilis, and autoimmune
conditions as well as from healthy controls were examined for
reactivity with VlsE by Western blotting and enzyme-linked
immunosorbent assay (ELISA). Strong Western blot
reactivity to a recombinant VlsE cassette region protein was
obtained consistently with Lyme disease sera. Although sera
from Lyme disease patients also reacted with a band
corresponding to VlsE in B. burgdorferi B31-5A3,
interpretation was complicated by low levels of VlsE
expression in in vitro-cultured B. burgdorferi and by the
presence of comigrating bands. An ELISA using recombinant
VlsE was compared with an ELISA using sonically disrupted
B. burgdorferi as the antigen. For a total of 93 Lyme disease
patient sera examined, the VlsE ELISA yielded sensitivities
of 63% for culture-confirmed erythema migrans cases and
92% for later stages, as compared to 61 and 98%,
respectively, for the "whole-cell" ELISA. The specificities of
the two assays with healthy blood donor sera were
comparable, but the VlsE ELISA was 90% specific with sera
from syphilis patients, compared to 20% specificity for the
whole-cell ELISA with this group. Neither assay showed
reactivity with a panel of sera from 20 non-Lyme disease
arthritis patients or 20 systemic lupus erythematosus
patients. Our results indicate that VlsE may be useful in the
immunodiagnosis of Lyme disease and may offer greater
specificity than ELISAs using whole B. burgdorferi as the
antigen.
CITATION IDS: PMID: 10565921 UI: 20033642
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=10565921&form=6&db=m&Dopt=b

TITLE: 
Sensitive and specific serodiagnosis of Lyme disease by
enzyme-linked immunosorbent assay with a peptide based on
an immunodominant conserved region of Borrelia burgdorferi
vlsE.
AUTHORS: 
Liang FT; Steere AC; Marques AR; Johnson BJ; Miller JN; Philipp MT
AUTHOR
AFFILIATION: 
Department of Parasitology, Tulane Regional Primate
Research Center, Tulane University Medical Center,
Covington, Louisiana 70433, USA.
GRANT/CONTRACT ID: 
AI35027/AI/NIAID
RR00164/RR/NCRR 
SOURCE: 
J Clin Microbiol 1999 Dec;37(12):3990-6
ABSTRACT: 
VlsE, the variable surface antigen of Borrelia burgdorferi,
contains an immunodominant conserved region named IR(6).
In the present study, the diagnostic performance of a peptide
enzyme-linked immunosorbent assay (ELISA) based on a
26-mer synthetic peptide (C(6)) with the IR(6) sequence was
explored. Sensitivity was assessed with serum samples (n =
210) collected from patients with clinically defined Lyme
disease at the acute (early localized or early disseminated
disease), convalescent, or late disease phase. The
sensitivities for acute-, convalescent-, and late-phase
specimens were 74% (29 of 39), 85 to 90% (34 of 40 to 35 of
39), and 100% (59 of 59), respectively. Serum specimens
from early neuroborreliosis patients were 95% positive (19 of
20), and those from an additional group of patients with
posttreatment Lyme disease syndrome yielded a sensitivity
of 62% (8 of 13). To assess the specificity of the peptide
ELISA, 77 serum samples from patients with other
spirochetal or chronic infections, autoimmune diseases, or
neurologic diseases and 99 serum specimens from
hospitalized patients in an area where Lyme disease is not
endemic were examined. Only two potential false positives
from the hospitalized patients were found, and the overall
specificity was 99% (174 of 176). Precision, which was
assessed with a panel of positive and negative serum
specimens arranged in blinded duplicates, was 100%. Four
serum samples with very high anti- OspA antibody titers
obtained from four monkeys given the OspA vaccine did not
react with the C(6) peptide. This simple, sensitive, specific,
and precise ELISA may contribute to alleviate some of the
remaining problems in Lyme disease serodiagnosis. Because
of its synthetic peptide base, it will be inexpensive to
manufacture. It also will be applicable to serum specimens
from OspA-vaccinated subjects.
CITATION IDS: PMID: 10565920 UI: 20033641
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=10565920&form=6&db=m&Dopt=b

TITLE: 
Association of antibiotic treatment-resistant Lyme arthritis with T
cell responses to dominant epitopes of outer surface protein A of
Borrelia burgdorferi [In Process Citation]
AUTHORS: Chen J; Field JA; Glickstein L; Molloy PJ; Huber BT; Steere AC
AUTHOR AFFILIATION:
Tufts University School of Medicine, Boston, Massachusetts, USA.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS
ABSTRACT:
OBJECTIVE: To explore further the association of antibiotic treatment-
resistant Lyme arthritis and T cell reactivity with outer surface
protein A (OspA) of Borrelia burgdorferi, including the
identification of T cell epitopes associated with this
treatment-resistant course. METHODS: The responses of peripheral
blood and, if available, synovial fluid lymphocytes to B burgdorferi
proteins, fragments, and synthetic peptides, as determined by
proliferation assay and interferon-gamma production, were compared in
16 patients with treatment-responsive and 16 with treatment-resistant
Lyme arthritis. RESULTS: The maximum severity of joint swelling
correlated directly with the response to OspA. Moreover, the only
significant difference between patients with treatment-resistant and
treatment-responsive arthritis was in reactivity with N-terminal and
C-terminal fragments of OspA, OspA1 (amino acids [aa] 16-106), and
OspA3 (aa 168-273). Epitope mapping showed that 14 of the 16 patients
with treatment-resistant arthritis had responses to OspA peptides
(usually 4 or 5 epitopes), whereas only 5 of the 16 patients with
treatment-responsive arthritis had reactivity with these peptides
(usually 1 or 2 epitopes) (P = 0.003). Patients with HLA-DRB1 alleles
associated with treatment-resistant arthritis were more likely to
react with peptide 15 (aa 154-173) and, to a lesser degree, with
peptide 21 (aa 214-233) than patients with other alleles, whereas the
responses to other epitopes were similar in both groups. CONCLUSION:
The maximum severity of joint swelling and the duration of Lyme
arthritis after antibiotic treatment are associated with T cell
responses to specific epitopes of OspA.
NLM PUBMED CIT. ID: 10513794 NLM CIT. ID: 99441952
SOURCE:  Arthritis Rheum 1999 Sep;42(9):1813-22
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=10513794&form=6&db=m&Dopt=b

TITLE: 
Successful treatment of Lyme encephalopathy with intravenous  
ceftriaxone.
AUTHORS: Logigian EL; Kaplan RF; Steere AC
AUTHOR AFFILIATION:
Department of Neurology, University of Rochester Medical Center,
Rochester, NY 14642, USA. elogigian@mail.neurology.rochester.edu
GRANT/CONTRACT ID: AR-20358/AR/NIAMS
ABSTRACT:
The efficacy of intravenous ceftriaxone, 2 g per day for 30 days, was
evaluated in a case series of 18 consecutive patients who met strict
criteria for Lyme encephalopathy. Months to years after classic
manifestations of Lyme disease, the 18 patients presented with memory
difficulty, minor depression, somnolence, or headache. Sixteen (89%)
had abnormal memory scores; 16 (89%) had cerebrospinal fluid (CSF)
abnormalities, and all 7 patients tested had frontotemporal perfusion
defects on single photon emission computed tomographic (SPECT)
imaging. Six months after treatment, memory scores in the 15 patients
who completed the study according to protocol were significantly
improved (P<.01). In the 10 patients who had follow-up CSF analyses,
total protein levels were significantly lower (P<.05). In the 7
patients who had SPECT imaging, posttreatment perfusion was
significantly better (P<.01). Twelve to 24 months after treatment,
all 18 patients rated themselves as back to normal or improved. We
conclude that Lyme encephalopathy can be treated successfully with
ceftriaxone.
NLM PUBMED CIT. ID: 10395852 NLM CIT. ID: 99326735
SOURCE:  J Infect Dis 1999 Aug;180(2):377-83
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=10395852&form=6&db=m&Dopt=b

TITLE: 
Cross-reactivity of Borrelia burgdorferi and myelin basic protein-
specific T cells is not observed in borrelial encephalomyelitis.
AUTHORS: Pohl-Koppe A; Logigian EL; Steere AC; Hafler DA
AUTHOR AFFILIATION:
Center for Neurologic Diseases, Brigham and Women's Hospital, Boston,
Massachusetts, 02115, USA.
Annette.Pohl-Koppe@kk-i.med.uni-muenchen.de
ABSTRACT:
Borrelial encephalomyelitis, a rare manifestation of Lyme borreliosis,
may present as a multiple sclerosis (MS)-like disease. It is
postulated that in MS, inflammation of the white matter is caused by
a T-cell response directed to myelin antigens. Here, we examined
whether a T- cell autoimmune response may play a pathogenetic role in
Borrelia- associated white matter disease mediated by
cross-reactivity between myelin basic protein (MBP) and B.
burgdorferi. We generated a total of 1760 short-term T-cell lines
against B. burgdorferi or MBP from two patients with Borrelial
encephalomyelitis and compared these with three patients with late
Lyme disease, one patient with transverse myelitis, eight patients
with MS, and four healthy controls. While a few T-cell lines
recognized both B. burgdorferi and MBP, T-cell clones from these
lines responded only to the antigen of the original stimulation.
Thus, our data do not provide evidence for cross-reactivity between
MBP and B. burgdorferi. Copyright 1999 Academic Press.
NLM PUBMED CIT. ID: 10357888 NLM CIT. ID: 99287759
SOURCE:  Cell Immunol 1999 May 25;194(1):118-23
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=10357888&form=6&db=m&Dopt=b

TITLE: 
The immunoglobulin (IgG) antibody response to OspA and OspB correlates
with severe and prolonged Lyme arthritis and the IgG response to P35
correlates with mild and brief arthritis.
AUTHORS: Akin E; McHugh GL; Flavell RA; Fikrig E; Steere AC
AUTHOR AFFILIATION:
Division of Rheumatology/Immunology, Tufts University School of
Medicine, New England Medical Center, Tupper Research Institute,
Boston, Massachusetts 02111, USA.
GRANT/CONTRACT ID: AR-20538/AR/NIAMS
ABSTRACT:
In an effort to implicate immune responses to specific Borrelia
burgdorferi proteins that may have a role in chronic Lyme arthritis,
we studied the natural history of the antibody response to B.
burgdorferi in serial serum samples from 25 patients monitored
throughout the course of Lyme disease. In these patients, the
immunoglobulin G (IgM) and IgG antibody responses to 10 recombinant
B. burgdorferi proteins, determined during early infection, early
arthritis, and maximal arthritis, were correlated with the severity
and duration of maximal arthritis. The earliest responses were
usually to outer surface protein C (OspC), P35, P37, and P41;
reactivity with OspE, OspF, P39, and P93 often developed weeks later;
and months to years later, 64% of patients had responses to OspA and
OspB. During early infection and early arthritis, the levels of IgG
antibody to P35 correlated inversely with the subsequent severity or
duration of maximal arthritis. In contrast, during periods of maximal
arthritis, the levels of IgG antibody to OspA and OspB, especially to
a C-terminal epitope of OspA, correlated directly with the severity
and duration of arthritis. Thus, the higher the IgG antibody response
to P35 earlier in the infection, the milder and briefer the
subsequent arthritis, whereas during maximal arthritis, the higher
the IgG response to OspA and OspB, the more severe and prolonged the
arthritis.
NLM PUBMED CIT. ID: 9864212 NLM CIT. ID: 99081739
SOURCE:  Infect Immun 1999 Jan;67(1):173-81
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9864212&form=6&db=m&Dopt=b

TITLE: 
Identification of LFA-1 as a candidate autoantigen in treatment-
resistant Lyme arthritis [see comments]
AUTHORS: Gross DM; Forsthuber T; Tary-Lehmann M; Etling C; 
Ito K; Nagy ZA; Field JA; Steere AC; Huber BT
AUTHOR AFFILIATION:
Department of Pathology, Tufts University, Boston, MA 02111 USA.
COMMENTS:
Comment in: Science 1998 Jul 31;281(5377):631-2
GRANT/CONTRACT ID: RO1 AR20358/AR/NIAMS
ABSTRACT:
Treatment-resistant Lyme arthritis is associated with immune
reactivity to outer surface protein A (OspA) of Borrelia burgdorferi,
the agent of Lyme disease, and the major histocompatibility complex
class II allele DRB1*0401. The immunodominant epitope of OspA for T
helper cells was identified. A homology search revealed a peptide
from human leukocyte function-associated antigen-1 (hLFA-1) as a
candidate autoantigen. Individuals with treatment-resistant Lyme
arthritis, but not other forms of arthritis, generated responses to
OspA, hLFA-1, and their highly related peptide epitopes.
Identification of the initiating bacterial antigen and a
cross-reactive autoantigen may provide a model for development of
autoimmune disease.
NLM PUBMED CIT. ID: 9685265 NLM CIT. ID: 98350208
SOURCE:  Science 1998 Jul 31;281(5377):703-6
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9685265&form=6&db=m&Dopt=b

TITLE: 
T helper 1 response is dominant and localized to the synovial fluid in
patients with Lyme arthritis.
AUTHORS: Gross DM; Steere AC; Huber BT
AUTHOR AFFILIATION:
Tufts University School of Medicine, Department of Pathology, Boston,
MA 02111, USA.
GRANT/CONTRACT ID: AI14910/AI/NIAID AI36696/AI/NIAID AR20358/AR/NIAMS
ABSTRACT:
Cytokines produced by subsets of CD4+ T helper cells responding to an
infection influences the efficiency with which the host is able to
mount a protective immune response. In an attempt to elucidate the
population of active cells involved in the propagation of Lyme
arthritis we have utilized intracellular cytokine staining to analyze
the polyclonal immune response at the single cell level. We have
determined the Th phenotype in the synovial fluid of patients with a
variety of chronic inflammatory arthritides, including patients
representative of the spectrum of Lyme arthritis. Th1 cells dominate
the immune response in the synovial fluid of patients with Lyme as
well as those with rheumatoid or other types of chronic inflammatory
arthritis. In addition, the severity of Lyme arthritis directly
correlates with the ratio of Th1 to Th2 cells in the synovial fluid,
such that the larger the effusion, the higher the ratio (r = 0.67, p
< 0.05). These results suggest that Th1 cells play a direct role in
the pathogenesis of the inflammatory process seen in Lyme arthritis,
and that Th2 cells modulate the pro-inflammatory response generated
by Th1 cells in the joint. Finally, we identify Th1 cells specific
for outer surface protein A of Borrelia burgdorferi, the agent of
Lyme disease. These cells are restricted to patients with Lyme
arthritis and are localized to the joint. Furthermore, they persist
in patients with prolonged antibiotic treatment-resistant Lyme
arthritis, suggesting the possibility of an autoimmune process.
NLM PUBMED CIT. ID: 9551943 NLM CIT. ID: 98211669
SOURCE:  J Immunol 1998 Jan 15;160(2):1022-8
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9551943&form=6&db=m&Dopt=b

TITLE: 
Neurocognitive abnormalities in children after classic manifestations
of Lyme disease.
AUTHORS: Bloom BJ; Wyckoff PM; Meissner HC; Steere AC
AUTHOR AFFILIATION:
Division of Rheumatology/Immunology, Tufts University School of
Medicine, and the Floating Hospital for Children, Boston, MA, USA.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS AR-07075/AR/NIAMS
ABSTRACT:
BACKGROUND: In adults a subtle encephalopathy characterized primarily
by memory impairment, irritability and somnolence may occur months to
years after classic manifestations of Lyme disease. However, only
limited information is available about whether there is an equivalent
disorder in children. METHODS: Case series of five children seen in a
Lyme disease clinic in a university referral center for evaluation of
neurocognitive symptoms that developed near the onset of infection or
months after classic manifestations of Lyme disease. The diagnosis
was based on clinical symptoms, serologic reactivity to Borrelia
burgdorferi and intrathecal antibody production to the spirochete.
Evaluation included detailed neuropsychologic testing. After
evaluation the children were treated with intravenous ceftriaxone for
2 or 4 weeks. Follow-up was done in the clinic and a final assessment
was made by telephone 2 to 7 years after treatment. RESULTS: Along
with or months after erythema migrans, cranial neuropathy or Lyme
arthritis, the five children developed behavioral changes,
forgetfulness, declining school performance, headache or fatigue and
in two cases a partial complex seizure disorder. All five patients
had IgG antibody responses to B. burgdorferi in serum as well as
intrathecal IgG antibody production to the spirochete. Two patients
had CSF pleocytoses and three did not. Despite normal intellectual
functioning the five children had mild to moderate deficits in
auditory or visual sequential processing. After ceftriaxone therapy,
the four children in whom follow- up information was available
experienced gradual improvement in symptoms. CONCLUSIONS: Children
may develop neurocognitive symptoms along with or after classic
manifestations of Lyme disease. This may represent an infectious or
postinfectious encephalopathy related to B. burgdorferi infection.
NLM PUBMED CIT. ID: 9535244 NLM CIT. ID: 98194892
SOURCE:  Pediatr Infect Dis J 1998 Mar;17(3):189-96
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9535244&form=6&db=m&Dopt=b

TITLE: 
Identification of a T cell subset capable of both IFN-gamma and IL-10
secretion in patients with chronic Borrelia burgdorferi infection.
AUTHORS: Pohl-Koppe A; Balashov KE; Steere AC; Logigian EL; Hafler DA
AUTHOR AFFILIATION:
Center for Neurologic Diseases, Department of Neurology, Brigham and
Women's Hospital, Boston, MA 02115, USA.
GRANT/CONTRACT ID: RO1-NS24247/NS/NINDS AR 43220/AR/NIAMS
ABSTRACT:
A novel population of both IFN-gamma- and IL-10-secreting human T
cells that differentiate in the presence of exogenous IL-12 in vitro
has recently been described. Whether this T cell population exists in
vivo is unknown. Borrelia burgdorferi, the etiologic agent of Lyme
disease, can induce a chronic infection in the presence of a vigorous
humoral immune response. We established T cell lines specific for B.
burgdorferi and tetanus toxoid from subjects with chronic B.
burgdorferi infection and healthy controls in limiting dilution
experiments and assessed proliferation and cytokine secretion. As
expected, higher frequencies of B. burgdorferi-specific precursor T
cells were observed in Lyme patients compared with controls. In both
groups of subjects, T cell lines specific for B. burgdorferi secreted
high amounts of IFN-gamma. However, in patients with Lyme disease,
27% of T cell lines secreted not only IFN-gamma but also IL-10, which
was only observed in 0.6% of B. burgdorferi-reactive T cell lines
generated from controls and in none of the tetanus toxoid-reactive T
cell lines generated from either Lyme patients and controls. Single
cell PHA cloning confirmed that both cytokines were secreted from one
clonally expanded precursor cell. Whole mononuclear cells from B.
burgdorferi- infected individuals, but not from controls, secreted
IL-12. Moreover, neutralizing anti-IL-12 mAbs inhibited the
generation of the IFN- gamma/IL-10 population. These data demonstrate
that this novel population of IL-12-induced IFN-gamma/IL-10-secreting
T cells is generated in response to chronic B. burgdorferi infection.
NLM PUBMED CIT. ID: 9469440 NLM CIT. ID: 98129342
SOURCE:  J Immunol 1998 Feb 15;160(4):1804-10
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9469440&form=6&db=m&Dopt=b

TITLE: 
Matrix metalloproteinases in the cerebrospinal fluid of patients with
Lyme neuroborreliosis.
AUTHORS: Perides G; Charness ME; Tanner LM; Peter O; Satz N; 
Steere AC; Klempner MS
AUTHOR AFFILIATION:
Tupper Research Institute, Tufts University School of Medicine, New
England Medical Center, Boston, Massachusetts 02111, USA.
george.perides@es.nemc.org
GRANT/CONTRACT ID: AI-37241/AI/NIAID AI-31610/AI/NIAID AI-65308/AI/NIAID
ABSTRACT:
Neurologic manifestations of Lyme disease include meningitis,
encephalopathy, and cranial and peripheral neuropathy. There are no
sensitive markers for neuroborreliosis, and diagnosis is often based
on clinical presentation and cerebrospinal fluid (CSF) abnormalities,
including intrathecal antibody production. Matrix metalloproteinase
(MMP) activity in CSF was compared in patients with neuroborreliosis,
patients with diverse neurologic disorders, and healthy controls. The
CSF of 17 of 18 healthy subjects and 33 of 37 patients with
neurologic symptoms and normal CSF and imaging studies contained only
MMP2. The CSF of several patients with neurologic disorders contained
MMP2, MMP9, and gelatinolytic activity at 130 and 250 kDa. The
130-kDa MMP was found without the 92-kDa MMP9 in the CSF of 11 (79%)
of 14 patients with neuroborreliosis and only 7 (6%) of 118 control
patients (P < .001). This pattern of CSF gelatinase activity may be a
useful marker for neuroborreliosis.
NLM PUBMED CIT. ID: 9466528 NLM CIT. ID: 98126004
SOURCE:  J Infect Dis 1998 Feb;177(2):401-8
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9466528&form=6&db=m&Dopt=b

TITLE: 
Test-treatment strategies for patients suspected of having Lyme
disease: a cost-effectiveness analysis.
AUTHORS: Nichol G; Dennis DT; Steere AC; Lightfoot R; Wells G; 
Shea B; Tugwell P
AUTHOR AFFILIATION:
Ottawa Civic Hospital, Ontario, Canada.
ABSTRACT:
PURPOSE: To examine the cost-effectiveness of test-treatment
strategies for patients suspected of having Lyme disease. DATA
SOURCES: The medical literature was searched for information on
outcomes and costs. Expert opinion was sought for information on
utilities. STUDY SELECTION: Articles that described patient
population, diagnostic criteria, dose and duration of therapy, and
criteria for assessment of outcomes. DATA EXTRACTION: The decision
analysis evaluated the following strategies: 1) no testing-no
treatment; 2) testing with enzyme-linked immunosorbent assay (ELISA)
followed by antibiotic treatment of patients with positive results;
3) two-step testing with ELISA followed by Western blot and
antibiotic treatment for patients with positive results on either
test; and 4) empirical antibiotic therapy. Three patient scenarios
were considered: myalgic symptoms, rash resembling erythema migrans,
and recurrent oligoarticular inflammatory arthritis. Results were
calculated as costs per quality- adjusted life-year and were
subjected to sensitivity analysis. Adjustment was made for the
diagnostic value of common clinical features of Lyme disease. DATA
SYNTHESIS: For myalgic symptoms without other features suggestive of
Lyme disease, the no testing-no treatment strategy was most
economically attractive (that is, had the most favorable
cost-effectiveness ratio). For rash, empirical antibiotic therapy was
less costly and more effective than other strategies. For
oligoarticular arthritis with a history of rash and tick bite,
two-step testing was associated with the lowest cost-effectiveness
ratio. Testing with ELISA and empirical antibiotic therapy cost an
additional $880,000 and $34,000 per quality-adjusted life-year,
respectively. For oligoarticular arthritis with one or no other
features suggestive of Lyme disease, two-step testing was most
economically attractive. CONCLUSIONS: Neither testing nor antibiotic
treatment is cost-effective if the pretest probability of Lyme
disease is low. Empirical antibiotic therapy is recommended if the
pretest probability is high, and two-step testing is recommended if
the pretest probability is intermediate.
NLM PUBMED CIT. ID: 9424980 NLM CIT. ID: 98069619
SOURCE:  Ann Intern Med 1998 Jan 1;128(1):37-48
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9424980&form=6&db=m&Dopt=b

TITLE: Laboratory evaluation in the diagnosis of Lyme disease.
AUTHORS: Tugwell P; Dennis DT; Weinstein A; Wells G; Shea B; 
Nichol G; Hayward R; Lightfoot R; Baker P; Steere AC
AUTHOR AFFILIATION:
University of Ottawa, Ontario, Canada.
ABSTRACT:
PURPOSE: To provide a qualitative evaluation of the predictive value
of the laboratory diagnosis of Lyme disease and to use the resultant
data to formulate guidelines for clinical diagnosis. DATA SOURCES: A
MEDLINE search of English-language articles or articles with
English-language abstracts published from 1982 to 1996. DATA
EXTRACTION: Sensitivity, specificity, and likelihood ratios were
calculated, and a random- effects model was used to combine the
proportions from the eligible studies. Prespecified criteria were
used to determine which studies were eligible for analysis. DATA
SYNTHESIS: Laboratory testing in general is not clinically useful if
the pretest probability of Lyme disease is less than 0.20 or greater
than 0.80. When the pretest probability is 0.20 to 0.80, sequential
testing with enzyme-linked immunosorbent assay and Western blot is
the most accurate method for ruling in or ruling out the possibility
of Lyme disease. CONCLUSIONS: Laboratory testing is recommended only
in patients whose pretest probability of Lyme disease is 0.20 to
0.80. If the pretest probability is less than 0.20, testing will
result in more false-positive results than true-positive results; a
negative test result in this situation effectively rules out the
disease.
NLM PUBMED CIT. ID: 9412316 NLM CIT. ID: 98049722
SOURCE:  Ann Intern Med 1997 Dec 15;127(12):1109-23
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9412316&form=6&db=m&Dopt=b

TITLE: Reversible cerebral hypoperfusion in Lyme encephalopathy.
AUTHORS: Logigian EL; Johnson KA; Kijewski MF; Kaplan RF; 
Becker JA; Jones KJ; Garada BM; Holman BL; Steere AC
AUTHOR AFFILIATION:
Department of Neurology, Brigham and Women's Hospital, Harvard Medical
School, Cambridge, MA, USA.
GRANT/CONTRACT ID: NS-31902/NS/NINDS AR-20358/AR/NIAMS
ABSTRACT:
Lyme encephalopathy (LE) presents with subtle neuropsychiatric
symptoms months to years after onset of infection with Borrelia
burgdorferi. Brain magnetic resonance images are usually normal. We
asked whether quantitative single photon emission computed tomography
(SPECT) is a useful method to diagnose LE, to measure the response to
antibiotic therapy, and to determine its neuroanatomic basis. In 13
patients with objective evidence of LE, SPECT demonstrated reduced
cerebral perfusion (mean perfusion defect index [PDI] = 255),
particularly in frontal subcortical and cortical regions. Six months
after treatment with 1 month of intravenous ceftriaxone, perfusion
significantly improved in all 13 patients (mean PDI = 188). In nine
patients with neuropsychiatric symptoms following Lyme disease, but
without objective abnormalities (e.g., possible LE), perfusion was
similar to that of the treated LE group (mean PDI = 198); six
possible LE patients (67%) had already received ceftriaxone prior to
our evaluation. Perfusion was significantly lower in patients with LE
and possible LE than in 26 normal subjects (mean PDI = 136), but 4
normal subjects (15%) had low perfusion in the LE range. We conclude
that LE patients have hypoperfusion of frontal subcortical and
cortical structures that is partially reversed after ceftriaxone
therapy. However, SPECT cannot be used alone to diagnose LE or
determine the presence of active CNS infection.
NLM PUBMED CIT. ID: 9409364 NLM CIT. ID: 98073829
SOURCE:  Neurology 1997 Dec;49(6):1661-70
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9409364&form=6&db=m&Dopt=b

TITLE: 
Cost effectiveness of oral as compared with intravenous antibiotic
therapy for patients with early Lyme disease or Lyme arthritis.
AUTHORS: Eckman MH; Steere AC; Kalish RA; Pauker SG
AUTHOR AFFILIATION:
Department of Medicine, New England Medical Center, Boston, MA 02111,
USA.
GRANT/CONTRACT ID: CCU110291
NO ABSTRACT AVAILABLE.
NLM PUBMED CIT. ID: 9233874 NLM CIT. ID: 97365060
SOURCE:  N Engl J Med 1997 Jul 31;337(5):357-63
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9233874&form=6&db=m&Dopt=b

TITLE: 
Detection of Borrelia burgdorferi DNA by polymerase chain reaction in
cerebrospinal fluid in Lyme neuroborreliosis.
AUTHORS: Nocton JJ; Bloom BJ; Rutledge BJ; Persing DH; 
Logigian EL; Schmid CH; Steere AC
AUTHOR AFFILIATION:
Division of Rheumatology/Immunology, New England Medical Center,
Boston, Massachusetts02111, USA.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS AR-41497/AR/NIAMS AI-32403/AI/NIAID
ABSTRACT:
A polymerase chain reaction (PCR) assay that detects Borrelia
burgdorferi DNA in cerebrospinal fluid (CSF) was evaluated as a
diagnostic test for acute or chronic Lyme neuroborreliosis. In one
laboratory, 102 samples were tested blindly, and 40 samples were
retested in a second laboratory. In the first laboratory, B.
burgdorferi DNA was detected in CSF samples in 6 (38%) of 16 patients
with acute neuroborreliosis, 11 (25%) of 44 with chronic
neuroborreliosis, and none of 42 samples from patients with other
illnesses. There was a significant correlation between PCR results
and the duration of previous intravenous antibiotic therapy. The
overall frequency of positive results was similar in the second
laboratory, but concordance between the laboratories and among
primer-probe sets was limited because many samples were positive with
only one primer-probe set. Thus, PCR testing can sometimes detect B.
burgdorferi DNA in CSF in patients with acute or chronic
neuroborreliosis, but with current methods, the sensitivity of the
test is limited.
NLM PUBMED CIT. ID: 8769624 NLM CIT. ID: 96365447
SOURCE:  J Infect Dis 1996 Sep;174(3):623-7
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8769624&form=6&db=m&Dopt=b

TITLE: Improved serodiagnostic testing for Lyme disease: results of a
multicenter serologic evaluation.
AUTHORS: Craven RB; Quan TJ; Bailey RE; Dattwyler R; Ryan RW; Sigal LH; 
Steere AC; Sullivan B; Johnson BJ; Dennis DT; Gubler DJ
AUTHOR AFFILIATION:
Centers for Disease Control and Prevention, Fort Collins, Colorado, USA.
NO ABSTRACT AVAILABLE.
NLM PUBMED CIT. ID: 8903216 NLM CIT. ID: 97064092
SOURCE:  Emerg Infect Dis 1996 Apr-Jun;2(2):136-40
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8903216&form=6&db=m&Dopt=b

TITLE: 
Dominant recognition of a Borrelia burgdorferi outer surface protein A
peptide by T helper cells in patients with treatment-resistant Lyme
arthritis.
AUTHORS: Kamradt T; Lengl-Janssen B; Strauss AF; Bansal G; Steere AC
AUTHOR AFFILIATION:
Division of Rheumatology, Immunology, Department of Medicine, New
England Medical Center Hospitals, Tufts University School of
Medicine, Boston, Massachusetts 02111, USA.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS AR-40567/AR/NIAMS
ABSTRACT:
In an earlier study, we found that T-cell lines (TCL) from five
patients with treatment-resistant Lyme arthritis preferentially
recognized Borrelia burgdorferi outer surface protein A (OspA), but
TCL from four patients with treatment-responsive arthritis only
rarely recognized this protein. Dominant T-cell recognition of an
arthritogenic OspA epitope is one way in which the immune response
against OspA might be involved in the pathogenesis of treatment-
resistant Lyme arthritis. In an effort to test this hypothesis, we
mapped the epitopes of 31 OspA-specific TCL and five T-cell clones
derived from the synovial fluid or peripheral blood samples of three
patients with treatment-resistant Lyme arthritis. Although each
patient's TCL recognized a broad array of OspA peptides with
different individual patterns, two regions of OspA were dominantly
recognized. Each patient's TCL dominantly recognized a C-terminal
epitope of OspA, ranging from amino acids (aa) 214 to 233 in one
patient to 244 to 263 in another, and the TCL of all three patients
dominantly recognized an epitope between aa 84 and 113. These
dominant regions were confirmed by clonal analysis in one patient.
Thus, the region of OspA between aa 84 and 113 was the dominant
T-cell epitope shared by these three patients with
treatment-resistant Lyme arthritis. If the T-cell response to OspA is
involved in the pathogenesis of treatment-resistant Lyme arthritis,
and epitope contained within aa 84 to 113 is a potentially
arthritogenic epitope.
NLM PUBMED CIT. ID: 8606091 NLM CIT. ID: 96178620
SOURCE:  Infect Immun 1996 Apr;64(4):1284-9
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8606091&form=6&db=m&Dopt=b

TITLE: Early and late antibody responses to full-length and truncated
constructs of outer surface protein A of Borrelia burgdorferi in Lyme
disease.
AUTHORS: Kalish RA; Leong JM; Steere AC
AUTHOR AFFILIATION:
Division of Rheumatology/Immunology, New England Medical Center, Tufts
University School of Medicine, Boston, Massachusetts 02111, USA.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS AR-07570/AR/NIAMS
ABSTRACT:
The immunoglobulin G (IgG) antibody response to outer surface protein
A (OspA) of Borrelia burgdorferi has been reported to occur late in
the course of Lyme disease. To learn when reactivity to particular
epitopes of OspA develops and whether the strength of particular
responses correlates with the duration of arthritis and HLA-DR
specificities, we determined the IgM and IgG responses by
enzyme-linked immunosorbent assay in 128 patients with various
manifestations of Lyme disease to full-length recombinant OspA and
three OspA fragments which divided the protein approximately into
thirds. Among the 10 patients who were followed serially, an early
IgM response was often found to epitopes in all three fragments of
OspA, sometimes accompanied by a weak IgG response, primarily to an
epitope in the middle third of the protein. Months to years later,
the seven patients who had prolonged or moderate episodes of
arthritis developed strong IgG responses to OspA, especially to
epitopes in the N-terminal and C-terminal fragments, that paralleled
the course of the arthritis. In single serum samples from 128
patients, a similar pattern of IgM and IgG reactivity with OspA
epitopes was seen in patients with early or late manifestations of
the illness. Of the 80 patients with arthritis, 62 (78%) had IgG
responses to OspA, usually with the strongest reactivity to the
C-terminal fragment. In these patients, the strength of the IgG
response to OspA correlated with the duration of arthritis; in
HLA-DR4-positive patients, most of whom had chronic arthritis, this
association was attributable to reactivity with the C-terminal
fragment. Thus, patients with Lyme disease often have early responses
to OspA, but those with prolonged arthritis do not develop IgG
responses to certain epitopes of the protein until late in the
illness. In patients with HLA-DR4, the strength of IgG reactivity
with one or more epitopes in the C-terminal fragment of OspA
correlates with the duration of arthritis.
NLM PUBMED CIT. ID: 7768602 NLM CIT. ID: 95286268
SOURCE:  Infect Immun 1995 Jun;63(6):2228-35
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=7768602&form=6&db=m&Dopt=b

TITLE: Clinical and serologic features of Lyme borreliosis in Russia.
AUTHORS: Ananjeva LP; Skripnikova IA; Barskova VG; Steere AC
AUTHOR AFFILIATION:
Rheumatology Institute, Moscow, Russia.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS
ABSTRACT:
OBJECTIVE. To describe clinical and serologic features of Lyme
borreliosis, particularly the joint abnormalities, in Russian
patients. METHODS. Physicians were invited to refer patients with
past or present erythema migrans to the Rheumatology Institute in
Moscow; field studies were done of residents in an area endemic for
Lyme borreliosis, and a serosurvey was conducted of patients with
nonspecific neurologic, cardiac, or joint symptoms. Serologic testing
was done by ELISA and Western blotting using a strain of Borrelia
afzelii, a member of the B. burgdorferi sensu lato complex, recovered
from ticks from the field study site. RESULTS. Of 86 patients with
erythema migrans, neurologic abnormalities developed in 26 (30%),
cardiac involvement in 5 (6%), arthritis or arthralgia in 35 (41%),
and acrodermatitis in 2 (2%). Joint involvement was usually
characterized by one or a few brief episodes of joint swelling or
pain in one large joint at a time. However, 69 of the 86 patients
(80%) received antibiotic therapy early in the infection. The
majority of patients with active infection had elevated levels of IgM
or IgG antibody to B. afzelii by ELISA, and those with late infection
often had IgG reactivity with > or = 5 spirochetal proteins,
particularly the 37, 39, 41, 60, and 93 kDa antigens. In a serosurvey
of 75 patients with facial palsy, atrioventricular block, or
arthritis or arthralgia of uncertain cause, 6 had IgG reactivity with
> or = 5 spirochetal proteins. CONCLUSION. Lyme borreliosis in Russia
is similar to that in other parts of Europe. Brief episodes of
arthritis or arthralgia were a common feature of the illness.
NLM PUBMED CIT. ID: 7791165 NLM CIT. ID: 95311260
SOURCE:  J Rheumatol 1995 Apr;22(4):689-94
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=7791165&form=6&db=m&Dopt=b

TITLE: [The clinical and serological manifestations of Lyme disease in
Russia]
VERNACULAR TITLE: 
Klinicheskie i serologicheskie proiavleniia laimskoi bolezni v Rossii.
AUTHORS: Anan'eva LP; Skripnikova IA; Barskova VG; Steere AC
ABSTRACT:
Out of 86 Lyme's disease patients with a history of migrating erythema
nervous system, cardiovascular and articular involvement was observed
in 27, 6 and 43% of cases. Acrodermatitis was diagnosed in 2% of
patients. Affection of locomotor system manifested with acute
arthritis episodes or pains in major joints. 11 patients of 12
examined at arthritis onset showed elevated titer of anti-Borrelia
IgG antibodies. Serologically, of 80 patients with arthritis or
arthralgia without prior migrating erythema 6 demonstrated antibodies
to 5 and more Borrelia polypeptides.
NLM PUBMED CIT. ID: 8571249 NLM CIT. ID: 96151293
SOURCE:  Ter Arkh 1995;67(11):38-42
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8571249&form=6&db=m&Dopt=b

TITLE: Lyme disease.
AUTHORS: Nocton JJ; Steere AC
AUTHOR AFFILIATION:
Division of Pediatric Rheumatology, Tufts University School of
Medicine, New England Medical Center, Boston, Massachusetts, USA.
NO ABSTRACT AVAILABLE.
NLM PUBMED CIT. ID: 7747659 NLM CIT. ID: 95266502
SOURCE:  Adv Intern Med 1995;40:69-117
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=7747659&form=6&db=m&Dopt=b

TITLE: 
The T helper cell response in Lyme arthritis: differential recognition
of Borrelia burgdorferi outer surface protein A in patients with
treatment-resistant or treatment-responsive Lyme arthritis.
AUTHORS: Lengl-Janssen B; Strauss AF; Steere AC; Kamradt T
AUTHOR AFFILIATION:
Department of Medicine, New England Medical Center Hospitals, Tufts
University School of Medicine, Boston, Massachusetts 02111.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS AR-40576/AR/NIAMS
ABSTRACT:
The host response to Borrelia burgdorferi is likely to play a role in
the pathogenesis of Lyme arthritis. Whereas most patients with Lyme
arthritis can be cured with antibiotic therapy, approximately 10% of
the patients have persistent arthritis for months or even several
years after antibiotic treatment. In this study, we tested the
hypothesis that the T cell response to one or more antigens of B.
burgdorferi is different in patients with treatment-responsive or
treatment-resistant Lyme arthritis. For this purpose, 313 B.
burgdorferi-specific T cell lines were derived from the synovial
fluid or peripheral blood of four patients with treatment-responsive
Lyme arthritis and five patients with treatment-resistant arthritis.
87 T cell lines from treatment- responsive Lyme arthritis and 112
lines from the treatment-resistant group were examined for the
recognition of five recombinant. B. burgdorferi proteins: outer
surface proteins A (OspA), B, C, p39, and p93. In both groups of
patients, the T cell lines frequently recognized OspB, and only
occasionally recognized OspC, p39, and p93. In contrast, OspA was
preferentially recognized by T cell lines from patients with
treatment-resistant arthritis, but only rarely recognized by T cell
lines from patients with treatment-responsive arthritis (odds ratio
28.4, 95% confidence interval 9.2-87.8, p < 0.005). These results are
compatible with the hypothesis that the T cell response to B.
burgdorferi OspA is involved in the pathogenesis of
treatment-resistant Lyme arthritis.
NLM PUBMED CIT. ID: 7964484 NLM CIT. ID: 95053741
SOURCE:  J Exp Med 1994 Dec 1;180(6):2069-78
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=7964484&form=6&db=m&Dopt=b

TITLE: 
The long-term clinical outcomes of Lyme disease. A population-based
retrospective cohort study [see comments]
AUTHORS: Shadick NA; Phillips CB; Logigian EL; Steere AC; Kaplan RF; 
Berardi VP; Duray PH; Larson MG; Wright EA; Ginsburg KS; et al
AUTHOR AFFILIATION:
Department of Rheumatology-Immunology, Brigham & Women's Hospital,
Boston, MA 02115.
COMMENTS:
Comment in: Ann Intern Med 1995 Jun 15;122(12):960-1; discussion 961-2
Comment in: Ann Intern Med 1995 Jun 15;122(12):961; discussion 961-2
GRANT/CONTRACT ID: AR07530/AR/NIAMS AR20358/AR/NIAMS AR36308/AR/NIAMS
ABSTRACT:
OBJECTIVE: To ascertain the prevalence of and risk factors for long-
term sequelae from acute Lyme disease. DESIGN: Population-based,
retrospective cohort study. SETTING: A coastal region endemic for
Lyme disease. PARTICIPANTS: Patients with a history of Lyme disease
who were previously treated with antibiotics were compared with
randomly selected controls. MEASUREMENTS: A standardized physical
examination, health status measure (Short Form 36), psychometric test
battery, and serologic analysis. RESULTS: Compared with the control
group (n = 43), the Lyme group (n = 38; mean duration from disease
onset to study evaluation, 6.2 years) had more arthralgias (61%
compared with 16%; P < 0.0001); distal paresthesias (16% compared
with 2%; P = 0.03); concentration difficulties (16% compared with 2%;
P = 0.03); and fatigue (26% compared with 9%; P = 0.04), and they had
poorer global health status scores (P = 0.04). The Lyme group also
had more abnormal joints (P = 0.02) and more verbal memory deficits
(P = 0.01) than did the control group. Overall, 13 patients (34%; 95%
CI, 19% to 49%) had long-term sequelae from Lyme disease (arthritis
or recurrent arthralgias [n = 6], neurocognitive impairment [n = 4],
and neuropathy or myelopathy [n = 3]). Compared with controls,
patients who had long- term sequelae had higher IgG antibody titers
to the spirochete (P = 0.03) and received treatment later (34.5
months compared with 2.7 months; P < 0.0001). CONCLUSIONS: Persons
with a history of Lyme disease have more musculoskeletal impairment
and a higher prevalence of verbal memory impairment when compared
with those without a history of Lyme disease. Our findings suggest
that disseminated Lyme disease may be associated with long-term
morbidity.
NLM PUBMED CIT. ID: 8085687 NLM CIT. ID: 94367953
SOURCE:  Ann Intern Med 1994 Oct 15;121(8):560-7
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8085687&form=6&db=m&Dopt=b

TITLE: Humoral immune response to outer surface protein C of Borrelia
burgdorferi in Lyme disease: role of the immunoglobulin M response in
the serodiagnosis of early infection.
AUTHORS: Fung BP; McHugh GL; Leong JM; Steere AC
AUTHOR AFFILIATION:
Division of Rheumatology/Immunology, New England Medical Center,
Boston, Massachusetts 02111.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS AR-40576/AR/NIAMS
ABSTRACT:
We determined the humoral immune response to outer surface protein C
(OspC) of Borrelia burgdorferi in patients with early or late
manifestations of Lyme disease and investigated the use of this
antigen in the serodiagnosis of early infection. The ospC gene from
the low- passage human isolate 297, a North American B. burgdorferi
strain, was used to make a recombinant maltose-binding protein
(MBP)-OspC fusion protein for serologic tests. This gene showed 84 to
85% nucleotide sequence identity and 76 to 79% amino acid identity
with ospC of B. burgdorferi B31 and 2591. The antibody responses to
MBP-OspC were determined in serial sera from 15 patients with Lyme
disease who were monitored for 4 to 12 years of illness, in
single-serum samples from 189 patients with early or late
manifestations of the disorder, and in serum samples from 106 control
patients. Early in the infection, patients with erythema migrans or
meningitis commonly had weak to strong immunoglobulin M (IgM)
responses to OspC and sometimes weak to moderate IgG responses.
Months to years later, weak to strong IgG reactivity with this
protein was often apparent in patients with arthritis, but this
response was weak or absent in patients with chronic
neuroborreliosis. When acute- and convalescent-phase serum samples
from patients with erythema migrans were tested for reactivity
against MBP-OspC, the sensitivity of the IgM test was 73% and the
specificity was 98%, with either enzyme-linked immunosorbent assay
(ELISA) or Western blotting. We conclude that the majority of
patients with Lyme disease have a prominent IgM response to OspC
early in the illness, which is often followed by a prominent IgG
response in patients with arthritis. For the serodiagnosis of early
infection, the sensitivity and specificity of IgM ELISA and Western
blotting were comparable or slightly improved when MBP-OspC was used
as the antigen compared with tests in which spirochetal lysates were
used.
NLM PUBMED CIT. ID: 8039891 NLM CIT. ID: 94314437
SOURCE:  Infect Immun 1994 Aug;62(8):3213-21
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8039891&form=6&db=m&Dopt=b

TITLE: 
Successful treatment of a patient with chronic Lyme arthritis with
extracorporeal photochemotherapy.
AUTHORS: Randazzo JP; DiSpaltro FX; Cottrill C; Klainer AS; Steere AC; 
Bisaccia E
AUTHOR AFFILIATION:
Department of Medicine, Columbia University College of Physicians &
Surgeons, New York, New York.
ABSTRACT:
We report the use of photopheresis in a patient with chronic Lyme
arthritis with apparent resolution of the signs and symptoms. Further
controlled trials will be required to determine whether there is a
therapeutic role for photopheresis in this disease.
NLM PUBMED CIT. ID: 8169273 NLM CIT. ID: 94222907
SOURCE:  J Am Acad Dermatol 1994 May;30(5 Pt 2):908-10
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8169273&form=6&db=m&Dopt=b

TITLE: 
Borrelia burgdorferi and Escherichia coli lipopolysaccharides induce
nitric oxide and interleukin-6 production in cultured rat brain
cells.
AUTHORS: Tatro JB; Romero LI; Beasley D; Steere AC; Reichlin S
AUTHOR AFFILIATION:
Division of Endocrinology, New England Medical Center Hospitals,
Boston, MA 02111.
GRANT/CONTRACT ID: MH-44694/MH/NIMH DK-16684/DK/NIDDK HL-47569/HL/NHLBI
ABSTRACT:
Borrelia burgdorferi, the spirochetal agent of Lyme disease, infects
the central nervous system (CNS), but the factors that mediate
inflammation and neurologic dysfunction are not known. Sonicated B.
burgdorferi stimulated in a concentration-dependent manner the
production of nitric oxide (NO) in glial-enriched primary cultures of
neonatal rat brain cells via induction of NO synthase activity.
Lipopolysaccharide (LPS) of Escherichia coli also stimulated nitrite
accumulation in a concentration-dependent manner. Stimulation of NO
production by B. burgdorferi sonicate and E. coli LPS was associated
with increased levels of mRNA coding for the cytokine-inducible form
of NO synthase. B. burgdorferi sonicate also stimulated release of
interleukin-6, with a concentration-response relationship similar to
that for its stimulation of nitrite production, as did E. coli LPS. A
competitive antagonist of E. coli LPS, Rhodopseudomonas sphaeroides
lipid A, inhibited LPS-induced stimulation of NO synthase activity
but markedly potentiated that of B. burgdorferi, indicating that the
initial triggering mechanism of B. burgdorferi is distinct from that
of E. coli LPS. Induction of NO synthase by bacterial agents within
the brain may represent a common pathway of CNS inflammation and
neurotoxicity.
NLM PUBMED CIT. ID: 7513330 NLM CIT. ID: 94223056
SOURCE:  J Infect Dis 1994 May;169(5):1014-22
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=7513330&form=6&db=m&Dopt=b

TITLE: 
Antibody responses to the three genomic groups of Borrelia burgdorferi
in European Lyme borreliosis.
AUTHORS: Dressler F; Ackermann R; Steere AC
AUTHOR AFFILIATION:
Division of Rheumatology/Immunology, New England Medical Center, Tufts
University School of Medicine, Boston, Massachusetts 02111.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS AR-40576/AR/NIAMS
ABSTRACT:
The antibody responses to the three genomic groups of Borrelia
burgdorferi (B. burgdorferi sensu stricto, Borrelia garinii, and
Borrelia afzelii) were determined in 97 German patients with various
manifestations of Lyme borreliosis. The geometric mean antibody
titers in each patient group, determined by ELISA, were similar with
each antigen preparation. By Western blotting, however, patients with
meningopolyneuritis tended to respond to more spirochetal
polypeptides of B. garinii, the group 2 strain, whereas those with
arthritis recognized more antigens of B. afzelii, the group 3 strain
(P < .03), as did those with acrodermatitis. Only 1 patient each with
erythema migrans, arthritis, or acrodermatitis had weak reactivity
with outer surface protein A (OspA), and none responded to OspB. It
is concluded that differences among the three groups of B.
burgdorferi may result in variations in the antibody response in
European Lyme borreliosis.
NLM PUBMED CIT. ID: 8106763 NLM CIT. ID: 94149315
SOURCE:  J Infect Dis 1994 Feb;169(2):313-8
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8106763&form=6&db=m&Dopt=b

TITLE: 
Detection of Borrelia burgdorferi DNA by polymerase chain reaction in
synovial fluid from patients with Lyme arthritis [see comments]
AUTHORS: Nocton JJ; Dressler F; Rutledge BJ; Rys PN; 
Persing DH; Steere AC
AUTHOR AFFILIATION:
Division of Rheumatology/Immunology, New England Medical Center,
Boston, MA 02111.
COMMENTS:
Comment in: N Engl J Med 1994 Jan 27;330(4):282-3
GRANT/CONTRACT ID: AR-20358/AR/NIAMS AR-40576/AR/NIAMS AR-07570/AR/NIAMS
ABSTRACT:
BACKGROUND. Borrelia burgdorferi is difficult to detect in synovial
fluid, which limits our understanding of the pathogenesis of Lyme
arthritis, particularly when arthritis persists despite antibiotic
therapy. METHODS. Using the polymerase chain reaction (PCR), we
attempted to detect B. burgdorferi DNA in joint-fluid samples
obtained over a 17-year period. The samples were tested in two
separate laboratories with four sets of primers and probes, three of
which target plasmid DNA that encodes outer-surface protein A (OspA).
RESULTS. B. burgdorferi DNA was detected in 75 of 88 patients with
Lyme arthritis (85 percent) and in none of 64 control patients. Each
of the three OspA primer-probe sets was sensitive, and the results
were moderately concordant in the two laboratories (kappa = 0.54 to
0.73). Of 73 patients with Lyme arthritis that was untreated or
treated with only short courses of oral antibiotics, 70 (96 percent)
had positive PCR results. In contrast, of 19 patients who received
either parenteral antibiotics or long courses of oral antibiotics (>
or = 1 month), only 7 (37 percent) had positive tests (P < 0.001).
None of these seven patients had received more than two months of
oral antibiotic treatment or more than three weeks of intravenous
antibiotic treatment. Of 10 patients with chronic arthritis
(continuous joint inflammation for one year or more) despite multiple
courses of antibiotics, 7 had consistently negative tests in samples
obtained three months to two years after treatment. CONCLUSIONS. PCR
testing can detect B. burgdorferi DNA in synovial fluid. This test
may be able to show whether Lyme arthritis that persists after
antibiotic treatment is due to persistence of the spirochete.
NLM PUBMED CIT. ID: 8272083 NLM CIT. ID: 94097367
SOURCE:  N Engl J Med 1994 Jan 27;330(4):229-34
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8272083&form=6&db=m&Dopt=b

TITLE: 
Empiric parenteral antibiotic treatment of patients with fibromyalgia
and fatigue and a positive serologic result for Lyme disease. A cost-
effectiveness analysis [see comments]
AUTHORS: Lightfoot RW Jr; Luft BJ; Rahn DW; Steere AC; Sigal LH; 
Zoschke DC; Gardner P; Britton MC; Kaufman RL
AUTHOR AFFILIATION:
Division of Rheumatology, Kentucky Clinic J515, University of Kentucky
Medical Center, Lexington 40536-0284.
COMMENTS:
Comment in: Ann Intern Med 1993 Sep 15;119(6):518
Comment in: Ann Intern Med 1993 Sep 15;119(6):528-9
ABSTRACT:
PURPOSE: To examine the cost-effectiveness of empirical, parenteral
antibiotic treatment of patients with chronic fatigue and myalgia and
a positive serologic result for Lyme disease who lack classic
manifestations. DATA SOURCES: Peer-reviewed journals, opinion of
experts in the field, and published epidemiologic reports. STUDY
SELECTION: Consensus by authors on articles that indicated methods
for patient selection; on criteria used for diagnosis; on immunologic
methods used for classifying patients; on the dose and duration of
therapy; and on criteria by which responses to therapy were
ascertained. DATA EXTRACTION: In a cost-effectiveness model, the
costs and benefits of empirical parenteral therapy for patients
seropositive for Lyme disease were compared with a strategy in which
only patients having classical symptoms of Lyme disease were treated.
DATA SYNTHESIS: In areas endemic for Lyme disease, the incidence of
false-positive serologic results in patients with nonspecific myalgia
or fatigue exceeds by four to one the incidence of true-positive
results in patients with nonclassical infections. Treatment of the
former group of patients costs $86,221 for each true-positive patient
treated. The empirical strategy causes 29 cases of drug toxicity for
every case in the more conservative strategy. If patients were
willing to pay $3485 to eliminate anxiety about not treating possible
true Lyme disease, the empirical strategy would break even.
CONCLUSION: For most patients with a positive Lyme antibody titer
whose only symptoms are nonspecific myalgia or fatigue the risks and
costs of empirical parenteral antibiotic therapy exceed the benefits.
Only when the value of patient anxiety about leaving a positive test
untreated exceeds the cost of such therapy is the empirical treatment
cost-effective.
NLM PUBMED CIT. ID: 8357117 NLM CIT. ID: 93362816
SOURCE:  Ann Intern Med 1993 Sep 15;119(6):503-9
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8357117&form=6&db=m&Dopt=b

TITLE: 
Reactivity of neuroborreliosis patients (Lyme disease) to cardiolipin
and gangliosides.
AUTHORS: Garcia Monco JC; Wheeler CM; Benach JL; Furie RA; 
Lukehart SA; Stanek G; Steere AC
AUTHOR AFFILIATION:
Department of Pathology, SUNY, Stony Brook 11794.
GRANT/CONTRACT ID: AR 40455/AR/NIAMS
ABSTRACT:
A subset of patients (50%) with neuroborreliosis (Lyme disease) showed
IgG reactivity to cardiolipin in solid phase ELISA. In addition, a
subset of patients with neuroborreliosis (29%) and syphilis (59%) had
IgM reactivity to gangliosides with a Gal(beta 1-3) GalNac terminal
sequence (GM1, GD1b, and asialo GM1). Anti-ganglioside IgM antibodies
were significantly more frequent in these two groups of patients
compared to patients with cutaneous and articular Lyme disease,
primary antiphospholipid syndrome, systemic lupus erythematosus and
normal controls. Correlative evidence and adsorption experiments
indicated that antibodies to cardiolipin had separate specificities
from those directed against the gangliosides. IgM antibodies to
Gal(beta 1-3) GalNac gangliosides appeared to have similar
specificities since these were positively correlated and inhibitable
by cross adsorption assays. Given the clinical associations of
patients with neuroborreliosis and syphilis with IgM reactivity to
gangliosides sharing the Gal(beta 1-3) GalNac terminus, we suggest
that these antibodies could represent a response to injury in
neurological disease or a cross reactive event caused by spirochetes.
NLM PUBMED CIT. ID: 8410057 NLM CIT. ID: 94015144
SOURCE:  J Neurol Sci 1993 Jul;117(1-2):206-14
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8410057&form=6&db=m&Dopt=b

TITLE: 
Association of treatment-resistant chronic Lyme arthritis with HLA-DR4
and antibody reactivity to OspA and OspB of Borrelia burgdorferi.
AUTHORS: Kalish RA; Leong JM; Steere AC
AUTHOR AFFILIATION:
Division of Rheumatology/Immunology, New England Medical Center, Tufts
University School of Medicine, Boston, Massachusetts 02111.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS AR-40576/AR/NIAMS AR-07570/AR/NIAMS
ABSTRACT:
Chronic Lyme arthritis that is unresponsive to antibiotic therapy is
associated with an increased frequency of the HLA-DR4 specificity. To
determine whether the immune response to a particular polypeptide of
Borrelia burgdorferi may be associated with treatment-resistant
chronic Lyme arthritis, we correlated the clinical courses and HLA-DR
specificities of 128 patients with Lyme disease with their antibody
responses to spirochetal polypeptides. Antibody reactivity was
determined by Western blotting (immunoblotting) with sonicated whole
B. burgdorferi and recombinant forms of its outer surface proteins,
OspA and OspB, as the antigen preparations. Of 15 patients monitored
for 4 to 12 years, 11 (73%) developed strong immunoglobulin G
responses to both OspA and OspB near the beginning of prolonged
episodes of arthritis, from 5 months to 7 years after disease onset.
When single serum samples from 80 patients with Lyme arthritis, were
tested, 57 (71%) showed antibody reactivity to recombinant Osp
proteins; in contrast, none of 43 patients who had erythema migrans
or Lyme meningitis (P < 0.00001) and 1 of 5 patients who had chronic
neuroborreliosis but who never had arthritis (P = 0.03) showed
antibody reactivity to these proteins. Among the 60
antibiotic-treated patients with Lyme arthritis, those with the
HLA-DR4 specificity and Osp reactivity had arthritis for a
significantly longer time after treatment than those who lacked Osp
reactivity (median duration, 9.5 versus 4 months; P = 0.009); a
similar trend was found for the HLA-DR2 specificity. For other HLA-DR
specificities, arthritis resolved within a median duration of 2
months in both Osp-reactive and nonreactive patients. We conclude
that the combination of the HLA-DR4 specificity and OspA or OspB
reactivity is associated with chronic arthritis and the lack of a
response to antibiotic therapy.
NLM PUBMED CIT. ID: 7685738 NLM CIT. ID: 93293292
SOURCE:  Infect Immun 1993 Jul;61(7):2774-9
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=7685738&form=6&db=m&Dopt=b

TITLE: Expression of public idiotypes in patients with Lyme arthritis.
AUTHORS: Axford JS; Watts RA; Long AA; Isenberg DA; Steere AC
AUTHOR AFFILIATION:
Academic Rheumatology Unit, St George's Hospital Medical School,
London, United Kingdom.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS AR-40576/AR/NIAMS
ABSTRACT:
OBJECTIVE: Joints are often affected in Lyme disease and in some
instances this may be due to immune autoreactivity. To characterise
further the immune response in this disease investigations were
carried out to determine the expression of three public idiotypes on
serum immunoglobulins in patients with Lyme disease during the
development of varying degrees of arthritis. METHODS: The expression
of idiotypes (Ids) 16/6, BEG2, and PR4, first identified on
monoclonal antibodies to DNA, was determined by an enzyme linked
immunosorbent assay (ELISA) in serial blood samples from 12 patients
with Lyme disease over a mean period of six years during the
development of a variety of arthritic symptoms, and in serum samples
from healthy control subjects and control subjects with systemic
lupus erythematosus. RESULTS: Expression of serum IgM or IgG public
Ids 16/6 and BEG2 was significantly increased in patients with Lyme
disease. IgA Id 16/6 expression, in contrast, was significantly
increased only during episodes of arthritis and was also related to
its severity. IgM and IgG Id 16/6 expression was related to their
respective total immunoglobulin concentration and, in the case of
IgM, to the level of IgM antibodies to Borrelia burgdorferi, whereas
similar findings were not apparent with IgA antibodies. This may
indicate that the IgA response is related to the pathogenesis of
arthritis, especially as total IgA and IgA Id 16/6 levels were found
to increase over the duration of disease. Sequential analysis of
antibodies also showed restriction in the expression of Id 16/6 as it
was never found on all immunoglobulin isotypes at the same time, and
Id PR4 was never expressed. Ids 16/6 and BEG2 expression, however,
may be associated as seven patients expressed these idiotypes
simultaneously. CONCLUSIONS: These data indicate the use of public
idiotypes in the immune response against B burgdorferi, which may be
restricted in terms of idiotype class and isotype expression, and a
possible association between IgA antibodies bearing Id 16/6 with
arthritis.
NLM PUBMED CIT. ID: 8484672 NLM CIT. ID: 93249298
SOURCE:  Ann Rheum Dis 1993 Mar;52(3):199-205
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8484672&form=6&db=m&Dopt=b

TITLE: Nonprotein antigens of Borrelia burgdorferi.
AUTHORS: Wheeler CM; Garcia Monco JC; Benach JL; Golightly MG; 
Habicht GS; Steere AC
AUTHOR AFFILIATION:
State of New York Department of Health, State University of New York,
Stony Brook 11794.
GRANT/CONTRACT ID: AR-40445/AR/NIAMS AR-36028/AR/NIAMS AR-20358/AR/NIAMS
ABSTRACT:
Preparative thin-layer chromatograms of chloroform-methanol extracts
of Borrelia burgdorferi (B31) sonicates showed four fractions (Rf
values of 0.84, 0.81, 0.66 and 0.61) that stained with iodine vapors,
orcinol, or phospray, suggesting the presence of lipid-,
carbohydrate-, and phosphorus-containing compounds. Sera from
patients with Lyme disease showed IgM or IgG antibody reactivity to
hydrophobic fractions, designated F1 and F2, in both early and late
stages of the disease. Lack of constitutive amino acids in these
fractions was shown by protein, amino acid, and peptide detection
analyses. Sera from patients with syphilis, systemic lupus
erythematosus, and antiphospholipid syndrome reacted to one or both
of the fractions. Adsorption of sera from Lyme disease patients with
intact B. burgdorferi resulted in significantly different pre- and
postadsorption patterns of reactivity by whole cell ELISA, whereas
adsorption with F1 and F2 resulted in similar pre- and postadsorption
patterns. These fractions may not be present in aqueous whole cell or
whole cell lysate ELISA antigens or in immunoblots.
NLM PUBMED CIT. ID: 8440937 NLM CIT. ID: 93179790
SOURCE:  J Infect Dis 1993 Mar;167(3):665-74
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8440937&form=6&db=m&Dopt=b

TITLE: 
Western blotting in the serodiagnosis of Lyme disease [see comments]
AUTHORS: Dressler F; Whalen JA; Reinhardt BN; Steere AC
AUTHOR AFFILIATION:
Division of Rheumatology/Immunology, Tufts University School of
Medicine, New England Medical Center, Boston, Massachusetts 02111.
COMMENTS:
Comment in: J Infect Dis 1993 Oct;168(4):1073
GRANT/CONTRACT ID: AR-20358/AR/NIAMS AR-40576/AR/NIAMS
ABSTRACT:
There are currently no accepted criteria for positive Western blots in
Lyme disease. In a retrospective analysis of 225 case and control
subjects, the best discriminatory ability of test criteria was
obtained by requiring at least 2 of the 8 most common IgM bands in
early disease (18, 21, 28, 37, 41, 45, 58, and 93 kDa) and by
requiring at least 5 of the 10 most frequent IgG bands after the
first weeks of infection (18, 21, 28, 30, 39, 41, 45, 58, 66, and 93
kDa). When these definitions were tested in a prospective study of
all 237 patients seen in a diagnostic Lyme disease clinic during a
1-year period and in 74 patients with erythema migrans or summer
flu-like illnesses, the IgM blot in early disease had a sensitivity
of 32% and a specificity of 100%; the IgG blot after the first weeks
of infection had a sensitivity of 83% and a specificity of 95%. Among
patients with indeterminate IgG responses by ELISA, 6 of 9 patients
with active Lyme disease had positive blots compared with 2 of 34
patients with other illnesses (P < .001). Thus, Western blotting can
be used to increase the specificity of serologic testing in Lyme
disease.
NLM PUBMED CIT. ID: 8380611 NLM CIT. ID: 93132390
SOURCE:  J Infect Dis 1993 Feb;167(2):392-400
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8380611&form=6&db=m&Dopt=b

TITLE: 
Balance of synovial fluid IL-1 beta and IL-1 receptor antagonist and
recovery from Lyme arthritis [see comments]
AUTHORS: Miller LC; Lynch EA; Isa S; Logan JW; Dinarello CA; Steere AC
AUTHOR AFFILIATION:
Department of Pediatrics, Tufts-New England Medical Center, Boston,
Massachusetts 02111.
COMMENTS:
Comment in: Lancet 1993 Jan 16;341(8838):155-6
ABSTRACT:
Borrelia burgdorferi, the causative agent of Lyme disease, is a potent
inducer of interleukin-1 beta (IL-1 beta), a cytokine implicated in
the pathogenesis of inflammatory arthritis. The balance between IL-1
and the IL-1 receptor antagonist (IL-1ra), a naturally occurring
inhibitor of IL-1, might influence disease expression. To explore
this possibility, we have done a retrospective study that compared
the clinical course of Lyme arthritis in 83 patients with
concentrations of IL-1 beta and IL-1ra in the patients' synovial
fluid. Patients with high concentrations of IL-1ra and low
concentrations of IL-1 beta had rapid resolution of attacks of
arthritis, whereas patients with the reverse pattern of cytokine
concentrations had long intervals to recovery. Thus, the balance
between synovial fluid IL-1 beta and IL-1ra concentrations relates to
the time to recovery from an episode of Lyme arthritis.
NLM PUBMED CIT. ID: 8093746 NLM CIT. ID: 93140438
SOURCE:  Lancet 1993 Jan 16;341(8838):146-8
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8093746&form=6&db=m&Dopt=b

TITLE: 
Live Borrelia burgdorferi preferentially activate interleukin-1 beta
gene expression and protein synthesis over the interleukin-1 receptor
antagonist.
AUTHORS: Miller LC; Isa S; Vannier E; Georgilis K; Steere AC; 
Dinarello CA
AUTHOR AFFILIATION:
Department of Pediatrics, New England Medical Center, Boston,
Massachusetts 02111.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS AR-40576/AR/NIAMS AI-15614/AI/NIAID
ABSTRACT:
Lyme arthritis is one of the few forms of chronic arthritis in which
the cause is known with certainty. Because cytokines are thought to
contribute to the pathogenesis of chronic arthritis, we investigated
the effect of the Lyme disease spirochete, Borrelia burgdorferi, on
the gene expression and synthesis of IL-1 beta and the IL-1 receptor
antagonist (IL-1ra) in human peripheral blood mononuclear cells. Live
B. burgdorferi induced fivefold more IL-1 beta than IL-1 alpha and
sevenfold more IL-1 beta than IL-1ra; LPS or sonicated B. burgdorferi
induced similar amounts of all three cytokines. This preferential
induction of IL-1 beta was most dramatic in response to a low
passage, virulent preparation of B. burgdorferi vs. three high
passage avirulent strains. No difference in induction of IL-1ra was
seen between these strains. The marked induction of IL-1 beta was
partially diminished by heat-treatment and abrogated by sonication;
IL-1ra was not affected. This suggested that a membrane component(s)
accounted for the preferential induction of IL-1 beta. However,
recombinant outer surface protein beta induced little IL-1 beta. By 4
h after stimulation, B. burgdorferi induced sixfold more IL-1 beta
protein than LPS. In contrast to LPS-induced IL-1 beta mRNA which
reached maximal accumulation after 3 h, B. burgdorferi-induced IL-1
beta mRNA showed biphasic elevations at 3 and 18 h. B.
burgdorferi-induced IL-1ra mRNA peaked at 12 h, whereas LPS-induced
IL-1ra mRNA peaked at 9 h. IL-1 beta synthesis increased in response
to increasing numbers of spirochetes, whereas IL-1ra synthesis did
not. The preferential induction by B. burgdorferi of IL-1 beta over
IL-1ra is an example of excess agonist over antagonist synthesis
induced by a microbial pathogen, and may contribute to the
destructive lesion of Lyme arthritis.
NLM PUBMED CIT. ID: 1387885 NLM CIT. ID: 92395169
SOURCE:  J Clin Invest 1992 Sep;90(3):906-12
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1387885&form=6&db=m&Dopt=b

TITLE: Lyme disease associated with fibromyalgia.
AUTHORS: Dinerman H; Steere AC
AUTHOR AFFILIATION:
Tufts University School of Medicine, Boston, Massachusetts.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS
ABSTRACT:
OBJECTIVE: To describe the clinical and laboratory findings as well as
results of treatment in patients with Lyme disease associated with
fibromyalgia. DESIGN: Observational cohort study. The mean duration
of observation was 2.5 years (range, 1 to 4 years). SETTING:
Diagnostic Lyme disease clinic in a university hospital. PATIENTS: Of
287 patients seen with Lyme disease during a 3.5-year period, 22 (8%)
had fibromyalgia associated with this illness, and 15 (5%)
participated in the observational study. MEASUREMENTS: Symptoms and
signs of fibromyalgia, immunodiagnostic tests for Lyme disease, and
tests of neurologic function. RESULTS: Of the 15 patients, 9
developed widespread musculoskeletal pain, tender points,
dysesthesias, memory difficulties, and debilitating fatigue a mean
duration of 1.7 months after early Lyme disease; the remaining six
patients developed those symptoms during the course of Lyme
arthritis. At the time of our evaluation, late in the course of their
illness, 11 patients had positive immunoglobulin (Ig) G antibody
responses to Borrelia burgdorferi by enzyme-linked immunosorbent 
assay (ELISA), one had a positive Western blot, and the three
seronegative patients had positive cellular immune responses to
borrelial antigens. Four patients had abnormal cerebrospinal fluid
analyses that showed an elevated protein level, a slight pleocytosis,
or intrathecal antibody production to the spirochete. The signs of
Lyme disease resolved with antibiotic therapy, usually intravenous
ceftriaxone, 2 g/d for 2 to 4 weeks, except in one patient with
persistent knee swelling. However, 14 of the 15 patients continued to
have symptoms of fibromyalgia. Currently, only one patient is
completely asymptomatic. CONCLUSIONS: Lyme disease may trigger
fibromyalgia, but antibiotics do not seem to be effective in the
treatment of the fibromyalgia.
NLM PUBMED CIT. ID: 1637022 NLM CIT. ID: 92344153
SOURCE:  Ann Intern Med 1992 Aug 15;117(4):281-5
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1637022&form=6&db=m&Dopt=b

TITLE: 
Memory impairment and depression in patients with Lyme encephalopathy:
comparison with fibromyalgia and nonpsychotically depressed patients.
AUTHORS: Kaplan RF; Meadows ME; Vincent LC; Logigian EL; Steere AC
AUTHOR AFFILIATION:
Department of Neurology, Tufts University School of Medicine, New
England Medical Center, Boston, MA 02111.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS
ABSTRACT:
Lyme encephalopathy, primarily manifested by disturbances in memory,
mood, and sleep, is a common late neurologic manifestation of Lyme
disease. We compared 20 patients with Lyme encephalopathy with 11
fibromyalgia patients and 11 nonpsychotically depressed patients
using the California Verbal Learning Test, Wechsler Memory Scale,
Rey- Osterrieth Complex Figure Test, Minnesota Multiphasic
Personality Inventory (MMPI), and Beck Depression Inventory. Compared
with patients with fibromyalgia or depression, the Lyme
encephalopathy group showed mild, but statistically significant,
memory deficits on two of the three memory tests. In contrast, the
patients with fibromyalgia scored significantly higher than both
other groups on the MMPI scale most sensitive to somatic concerns
(scale 1), while the depressed patients scored higher than the Lyme
patients on the scales most sensitive to depression (scale 2) and
anxiety (scale 7). Physical complaints and depression were not major
factors in memory performance among Lyme patients. These data support
the hypothesis that Lyme encephalopathy is caused by CNS dysfunction
and cannot be explained as a psychological response to chronic
illness.
NLM PUBMED CIT. ID: 1620329 NLM CIT. ID: 92319273
SOURCE:  Neurology 1992 Jul;42(7):1263-7
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1620329&form=6&db=m&Dopt=b

TITLE: Treatment of early Lyme disease [see comments]
AUTHORS: Massarotti EM; Luger SW; Rahn DW; Messner RP; 
Wong JB; Johnson RC; Steere AC
AUTHOR AFFILIATION:
Division of Rheumatology, New England Medical Center, Tufts University
School of Medicine, Boston, Massachusetts 02111.
COMMENTS:
Comment in: Am J Med 1993 May;94(5):553
GRANT/CONTRACT ID: AR-20358/AR/NIAMS AR-34744/AR/NIAMS
ABSTRACT:
PURPOSE: To compare the safety and efficacy of azithromycin,
amoxicillin/probenecid, and doxycycline for the treatment of early
Lyme disease, to identify risk factors for treatment failure, and to
describe the serologic response in treated patients. PATIENTS AND
METHODS: Fifty-five patients with erythema migrans and two patients
with flu-like symptoms alone and fourfold changes in antibody titers
to Borrelia burgdorferi were randomized to receive (1) oral
azithromycin, 500 mg on the first day followed by 250 mg once a day
for 4 days; (2) oral amoxicillin 500 mg and probenecid 500 mg, three
times a day for each for 10 days; or (3) doxcycline, 100 mg twice a
day for 10 days. If symptoms were still present at 10 days, treatment
was extended with amoxicillin/probenecid or doxycycline for 10 more
days. Evaluations were done at study entry and 10, 30, and 180 days
later. RESULTS: Three of the patients who initially had symptoms
suggestive of spread of the spirochete to the nervous system, one
from each antibiotic treatment group, subsequently developed
neurologic abnormalities, but symptoms in the other 54 patients
resolved within 3 to 30 days after study entry. Six of the 19
patients (32%) (95% confidence interval, 13% to 57%) given
amoxicillin/probenecid developed a drug eruption, whereas none of the
patients given azithromycin or doxycycline had this complication. The
presence of dysesthesias at study entry was the only risk factor
significantly associated with treatment failure (p less than 0.001).
By convalescence, 72% of the patients were seropositive, and 56%
still had detectable IgM responses to the spirochete 6 months later.
CONCLUSIONS: The three antibiotic regimens tested in this study were
generally effective for the treatment of early Lyme disease, but the
regimens differ in the frequency of side effects and in ease of
administration.
NLM PUBMED CIT. ID: 1313637 NLM CIT. ID: 92214475
SOURCE:  Am J Med 1992 Apr;92(4):396-403
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1313637&form=6&db=m&Dopt=b

TITLE: [Epidemiological study of Lyme disease in Brazil]
VERNACULAR TITLE: 
Estudo epidemiologico da doenca de Lyme no Brasil.
AUTHORS: Hoshinari NH; Barros PJ; Yassuda P; Baggio D; Steere AC; 
Pagliarine RC; Cossermelli W
AUTHOR AFFILIATION:
Disciplina de Reumatologia, Faculdade de Medicina, Universidade de Sao
Paulo.
ABSTRACT:
Lyme disease is a tick-born infection first reported in United States
of America in 1977 by Allen C. Steere. It occurred in the state of
Connecticut; other cases have been discovered in others states of USA
and also in other countries (Canada, Soviet Union, Japan, China,
Australia). This disease has not been reported in South America yet.
In order to investigate this disease in Brasil, a multi-disciplinary
group including microbiologists, entomologists and clinicians was
created at the University of Sao Paulo. The aim of this report is to
describe the elaboration of this research in our center and also to
present the preliminary results.
NLM PUBMED CIT. ID: 1340016 NLM CIT. ID: 94023691
SOURCE:  Rev Hosp Clin Fac Med Sao Paulo 1992 Mar-Apr;47(2):71-5
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1340016&form=6&db=m&Dopt=b

TITLE: 
Clinical and electrophysiologic findings in chronic neuropathy of Lyme
disease.
AUTHORS: Logigian EL; Steere AC
AUTHOR AFFILIATION:
Department of Neurology, New England Medical Center, Boston, MA.
ABSTRACT:
We evaluated 25 patients with Lyme disease and chronic peripheral
neuropathy. All had immunologic evidence of exposure to Borrelia
burgdorferi and no other identifiable cause of neuropathy.
Neuropathic symptoms began a median of 8 months (range, 0 to 165)
after erythema migrans and had been present for a median of 12 months
(range, 2 to 168) prior to evaluation. Twelve patients (48%) had
generally symmetric distal, nonpainful paresthesia, and another 12
(48%) had generally asymmetric radicular pain. One patient (4%) had
asymptomatic neuropathy. The most common physical finding was
multimodal sensory loss, which was observed in 13 patients (52%);
weakness and hyporeflexia were less common. Motor or sensory nerve
conduction was slightly slow in 16 patients (64%). The paresthesia
group more often had abnormalities on physical examination and on
nerve conduction testing than did the radicular group. In 75% to 80%
of patients from both groups, however, needle examination showed
denervation in paraspinal and limb muscles. Among 20 patients who
underwent lumbar puncture, only one had a slight spinal fluid
pleocytosis. Six months after treatment with intravenous ceftriaxone,
19 patients (76%) were clinically improved. We conclude that Lyme
disease can be associated with a reversible, mild chronic axonal
sensorimotor polyradiculoneuropathy or polyradiculopathy.
NLM PUBMED CIT. ID: 1310529 NLM CIT. ID: 92140650
SOURCE:  Neurology 1992 Feb;42(2):303-11
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1310529&form=6&db=m&Dopt=b

TITLE: 
The T-cell proliferative assay in the diagnosis of Lyme disease [see
comments]
AUTHORS: Dressler F; Yoshinari NH; Steere AC
AUTHOR AFFILIATION:
Tufts University School of Medicine, New England Medical Center,
Boston, Massachusetts.
COMMENTS:
Comment in: Ann Intern Med 1992 Apr 1;116(7):603
GRANT/CONTRACT ID: AR-20358/AR/NIAMS AR-40576/AR/NIAMS
ABSTRACT:
OBJECTIVE: To determine the sensitivity and specificity of the T-cell
proliferative assay as a diagnostic test in Lyme disease. DESIGN:
Cross- sectional study of patients with Lyme arthritis or chronic
neuroborreliosis who had a history of erythema migrans, positive
antibody responses to Borrelia burgdorferi by enzyme-linked
immunosorbent assay (ELISA), or both; patients with other diseases;
and healthy subjects. SETTING: Diagnostic Lyme disease clinic in a
university hospital. PATIENTS: Forty-two of the 67 patients with
active Lyme arthritis or chronic neuroborreliosis who were seen
during the study period; 16 patients with inactive late Lyme disease;
77 patients with other rheumatologic or neurologic diseases; 9
workers from the Borrelia laboratory; and 9 healthy subjects.
MEASUREMENTS AND MAIN RESULTS: Nineteen of 42 patients with Lyme
arthritis or chronic neuroborreliosis and 4 of 77 patients with other
diseases had positive T-cell proliferative responses to B.
burgdorferi antigens. The sensitivity of the proliferative assay was
45% (95% Cl, 30% to 60%) and the specificity was 95% (95% Cl, 87% to
99%). Twelve of 27 patients with active Lyme arthritis, 7 of 15
patients with chronic neuroborreliosis, 4 of 16 patients with
inactive Lyme disease, 4 of 9 healthy Borrelia laboratory workers,
and 0 of 9 healthy subjects had positive responses. Three of five
patients with Lyme disease who had negative or indeterminant antibody
responses by ELISA had positive T- cell proliferative responses.
CONCLUSION: The T-cell proliferative assay may be a helpful
diagnostic test in the small subset of patients with late Lyme
disease who have negative or indeterminant antibody responses by
ELISA.
NLM PUBMED CIT. ID: 1883122 NLM CIT. ID: 91353920
SOURCE:  Ann Intern Med 1991 Oct 1;115(7):533-9
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1883122&form=6&db=m&Dopt=b

TITLE: Spirochetes in atrophic skin lesions accompanied by minimal host
response in a child with Lyme disease.
AUTHORS: Gellis SE; Stadecker MJ; Steere AC
AUTHOR AFFILIATION:
Department of Dermatology, Pathology, Tufts University School of
Medicine, Boston, MA.
GRANT/CONTRACT ID: AM-20358/AM/NIADDK
ABSTRACT:
Acrodermatitis chronica atrophicans, which has rarely been observed in
the United States, is a late skin manifestation of Lyme borreliosis.
A 12-year-old girl who spent summers on Cape Cod presented with a
2-year history of hyperpigmentation and atrophy of the skin on the
hands, wrists, and ankles. The skin biopsy specimen of an affected
area showed mild dermal fibrosis, a few inflammatory cells, and
spirochetes morphologically compatible with Borrelia burgdorferi. An
IgG antibody response to B. burgdorferi could be elicited by
immunoblotting, but not by enzyme-linked immunosorbent assay. We
conclude that this patient had chronic Lyme borreliosis manifested
only by indolent infection of the skin.
NLM PUBMED CIT. ID: 1894781 NLM CIT. ID: 91373632
SOURCE:  J Am Acad Dermatol 1991 Aug;25(2 Pt 2):395-7
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1894781&form=6&db=m&Dopt=b

TITLE: Treatment of refractory chronic Lyme arthritis with arthroscopic
synovectomy.
AUTHORS: Schoen RT; Aversa JM; Rahn DW; Steere AC
AUTHOR AFFILIATION:
Department of Medicine, Yale University School of Medicine, New Haven,
Connecticut 06510.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS
ABSTRACT:
Of 20 patients who underwent arthroscopic synovectomy for refractory
chronic Lyme arthritis of the knee, 16 (80%) had resolution of joint
inflammation during the first month after surgery or soon thereafter,
and they have remained well during the 3-8-year followup period.
Three of these 16 patients who were more disabled preoperatively,
still had mild functional limitation at long-term followup. The
remaining 4 patients (20%) had persistent or recurrent synovitis. We
conclude that arthroscopic synovectomy is effective in treating
chronic Lyme arthritis in patients in whom the disease does not
respond to antibiotic therapy.
NLM PUBMED CIT. ID: 1859481 NLM CIT. ID: 91315620
SOURCE:  Arthritis Rheum 1991 Aug;34(8):1056-60
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1859481&form=6&db=m&Dopt=b

TITLE: The long-term course of Lyme arthritis in children [see comments]
AUTHORS: Szer IS; Taylor E; Steere AC
AUTHOR AFFILIATION:
Department of Pediatrics, Floating Hospital for Infants and Children,
New England Medical Center, Tufts University School of Medicine,
Boston.
COMMENTS:
Comment in: N Engl J Med 1991 Dec 26;325(26):1886
GRANT/CONTRACT ID: AR-20358/AR/NIAMS
ABSTRACT:
BACKGROUND AND METHODS. The natural history of Lyme disease is not
completely known. We studied the long-term course of Lyme arthritis
in 46 children in whom the onset of the disease occurred between 1976
and 1979 and who received no antibiotic therapy for at least the
first four years of the illness. RESULTS. Of the 46 children (age
range, 2 to 15 years), 33 (72 percent) initially had erythema
migrans, 7 (15 percent) had influenza-like symptoms, and 6 (13
percent) had migratory joint pain. These manifestations were followed
by brief attacks of arthritis, particularly affecting the knee. The
percentage of children with recurrent episodes of arthritis declined
each year. By year 4, only 10 children still had a mean of two
episodes of arthritis per year; the duration of arthritis was
generally longer in older children (P less than 0.05). During the
sixth year of illness, two children (4 percent) had keratitis, and
more than 10 years after the onset of disease, a subtle
encephalopathy developed in two other children. Of the 39 children
whom we were able to contact in 1988-1989, 12 (31 percent) still had
occasional brief episodes of joint pain and 1 (3 percent) had marked
fatigue. All 46 children had positive IgG antibody responses to
Borrelia burgdorferi throughout the illness and on long-term
follow-up. As compared with those who became asymptomatic, the
children with recurrent symptoms more often had IgM responses to the
spirochete and had significantly higher IgG titers (P less than
0.05). CONCLUSIONS. The course of initially untreated Lyme disease in
children may include acute infection followed by attacks of arthritis
and then by keratitis, subtle joint pain, or chronic encephalopathy.
NLM PUBMED CIT. ID: 2052061 NLM CIT. ID: 91270328
SOURCE:  N Engl J Med 1991 Jul 18;325(3):159-63
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2052061&form=6&db=m&Dopt=b

TITLE: 
Neutrophil chemotactic factors in synovial fluids of patients with
Lyme disease.
AUTHORS: Georgilis K; Noring R; Steere AC; Klempner MS
AUTHOR AFFILIATION:
Division of Geographic Medicine and Infectious Diseases, Tufts
University School of Medicine, New England Medical Center Hospitals,
Boston 02111.
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AI-16732/AI/NIAID
ABSTRACT:
We examined synovial fluid samples from 14 patients with Lyme
arthritis for the presence of neutrophil chemotactic factors.
Thirteen of the synovial fluids stimulated chemotaxis of normal human
neutrophils. The chemotactic activity was heat-sensitive and was not
inhibited by antibody to C5a or antibody to interleukin-8, or by a
competitive inhibitor of the chemotactic peptide f-Met-Leu-Phe. A
culture supernatant of Borrelia burgdorferi also contained neutrophil
chemoattractants. Chromatography demonstrated that the
chemoattractants in the synovial fluid samples were different from
those in the B burgdorferi culture supernatant. One of the major
chemotactic factors in Lyme disease synovial fluid had a calculated
molecular weight of 13,900. We conclude that a novel, host-derived
chemoattractant is present in the synovial fluid of patients with
Lyme disease.
NLM PUBMED CIT. ID: 2053924 NLM CIT. ID: 91273652
SOURCE:  Arthritis Rheum 1991 Jun;34(6):770-5
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2053924&form=6&db=m&Dopt=b

TITLE: 
T cell responses to polypeptide fractions of Borrelia burgdorferi in
patients with Lyme arthritis.
AUTHORS: Yoshinari NH; Reinhardt BN; Steere AC
AUTHOR AFFILIATION:
Division of Rheumatology/Immunology, New England Medical Center, Tufts
University School of Medicine, Boston, MA 02111.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS
ABSTRACT:
Among 6 patients with prolonged episodes of Lyme arthritis, the mean
response of peripheral blood lymphocytes (PBL) to all Borrelia
burgdorferi antigens (stimulation index [SI] 46) was greater than
that among 5 patients with brief attacks of Lyme arthritis (SI 13; P
less than 0.1), as well as that among 7 control patients with
rheumatoid arthritis and among 6 normal control subjects (in both
instances SI 3; P less than 0.05). In individual patients with brief
episodes of Lyme arthritis, PBL had similar low levels of reactivity
with the 20-kd, 31- kd, 34-kd, 41-kd, 55/58-kd, and 66-kd spirochetal
polypeptides. In individual patients with prolonged arthritis, PBL
usually had similar marked responsiveness to the 34-kd, 41-kd,
55/58-kd, and 66-kd polypeptides, but they had greater reactivity
with the 34-kd outer surface protein B than with the 31-kd outer
surface protein A (P less than 0.05). In the 2 patients tested,
paired samples of synovial fluid lymphocytes and PBL had a similar
pattern of reactivity, but the response was 2-100-fold greater in
synovial fluid lymphocytes. We conclude that patients with prolonged
Lyme arthritis have T cell responses to multiple spirochetal
polypeptides.
NLM PUBMED CIT. ID: 2053916 NLM CIT. ID: 91273643
SOURCE:  Arthritis Rheum 1991 Jun;34(6):707-13
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2053916&form=6&db=m&Dopt=b

TITLE: 
Molecular analysis of the role of the HLA class II genes DRB1, DQA1,
DQB1, and DPB1 in susceptibility to Lyme arthritis.
AUTHORS: Ruberti G; Begovich AB; Steere AC; Klitz W; 
Erlich HA; Fathman CG
AUTHOR AFFILIATION:
Department of Medicine, Stanford University School of Medicine,
California 94305.
GRANT/CONTRACT ID: AM 20610/AM/NIADDK AI29042/AI/NIAID 
AM-20358/AM/NIADDK
ABSTRACT:
Using the polymerase chain reaction and sequence-specific
oligonucleotide probes, we have determined the distribution of the
alleles at the polymorphic class II loci, DRB1, DQA1, DQB1, and DPB1
in 25 patients with Lyme arthritis. Comparison of the frequencies of
the DRB1 and DPB1 alleles in Lyme arthritis patients to the Centre
d'Etude du Polymorphisme Humaine control panel revealed statistically
significant differences between the two groups. An increase in
DRB1*1301 is noted along with a unique distribution of the DR4
subtypes within the 9 DR4+ patients. In addition, an increase in the
rate DPB1*1001 and the more common DPB1*0201 alleles is reported.
NLM PUBMED CIT. ID: 1679052 NLM CIT. ID: 91349057
SOURCE:  Hum Immunol 1991 May;31(1):20-7
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1679052&form=6&db=m&Dopt=b

TITLE: 
Lyme arthritis: oligoclonal anti-Borrelia burgdorferi IgG antibodies
occur in joint fluid and serum.
AUTHORS: Cruz M; Hansen K; Ernerudh J; Steere AC; Link H
AUTHOR AFFILIATION:
Department of Neurology, Karolinska Institutet, Huddinge University
Hospital, Stockholm, Sweden.
GRANT/CONTRACT ID: AM-20358/AM/NIADDK
ABSTRACT:
The antibody response to Borrelia (B.) burgdorferi, and to measles
virus as control antigen, was analysed by agarose isoelectric
focusing (AIF) and immunoblot of joint fluid and serum from 10
patients with Lyme arthritis and 10 controls with rheumatoid
arthritis. Among the Lyme arthritis patients, six had oligoclonal
anti-B. burgdorferi IgG antibody bands in joint fluid and
corresponding serum, one patient had oligoclonal antibody bands in
joint fluid only and also an elevated B. burgdorferi-specific joint
fluid to serum antibody ratio as evidence of intra-joint production
of specific antibodies, and the remaining three patients were
negative for oligoclonal-specific antibody bands. Absorption with B.
burgdorferi antigen confirmed the specificity of the oligoclonal
antibody bands. They comigrated only partially on AIF with
oligoclonal bands of total IgG, and the specificity of most
oligoclonal IgG in joint fluid and serum in Lyme arthritis remains
undefined. Among the controls, no anti-B, burgdorferi IgG antibodies
were detected by AIF and immunoblot. Instead, 9 of the 10 rheumatoid
arthritis patients had oligoclonal anti-measles IgG antibody bands
which were restricted to the joint fluid in three of them, indicating
local production. We conclude that Lyme arthritis is often
accompanied by an oligoclonal specific antibody response in joint
fluid and serum simultaneously, and occasionally by intrasynovial
synthesis of oligoclonal-specific antibodies.
NLM PUBMED CIT. ID: 1996408 NLM CIT. ID: 91142700
SOURCE:  Scand J Immunol 1991 Jan;33(1):61-71
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1996408&form=6&db=m&Dopt=b

TITLE: Infectivity of Borrelia burgdorferi correlates with resistance to
elimination by phagocytic cells.
AUTHORS: Georgilis K; Steere AC; Klempner MS
AUTHOR AFFILIATION:
Department of Medicine, Tufts University School of Medicine, New
England Medical Center Hospitals, Boston, Massachusetts 02111.
GRANT/CONTRACT ID: AI-16732/AI/NIAID AM-20358/AM/NIADDK
ABSTRACT:
The Lyme disease spirochete, Borrelia burgdorferi, causes a
disseminated infection in vivo, implying resistance to clearance by
phagocytic cells. Because B. burgdorferi loses its infectivity after
in vitro cultivation, the relationships between serial passaging of
the organism in vitro, its susceptibility to elimination by
phagocytes, and its infectivity were examined. When three different
high-passage strains were incubated for 4 h at 37 degrees C with
peripheral blood mononuclear cells, macrophages, or polymorphonuclear
neutrophils, 45%- 67% of the organisms were eliminated. In contrast,
two low-passage strains were resistant to elimination by phagocytes,
and only 5%-6% of the organisms were removed after 4 h. All five
strains equally stimulated the neutrophil oxidative burst, indicating
that evasion of phagocytes was not a result of avoidance of
recognition by these cells. The two low-passage strains were
infective when injected into mice, whereas the three high-passage
ones were not. These observations indicate that infectivity of the
Lyme disease spirochete correlates with resistance to elimination by
phagocytic cells.
NLM PUBMED CIT. ID: 1984461 NLM CIT. ID: 91079640
SOURCE:  J Infect Dis 1991 Jan;163(1):150-5
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1984461&form=6&db=m&Dopt=b

TITLE: Chronic neurologic manifestations of Lyme disease [see comments]
AUTHORS: Logigian EL; Kaplan RF; Steere AC
AUTHOR AFFILIATION:
Department of Neurology, Tufts University School of Medicine, Boston,
MA 02111.
COMMENTS:
Comment in: N Engl J Med 1991 Apr 18;324(16):1137
GRANT/CONTRACT ID: AM-20358/AM/NIADDK
ABSTRACT:
BACKGROUND AND METHODS. Lyme disease, caused by the tick-borne
spirochete Borrelia burgdorferi, is associated with a wide variety of
neurologic manifestations. To define further the chronic neurologic
abnormalities of Lyme disease, we studied 27 patients (age range, 25
to 72 years) with previous signs of Lyme disease, current evidence of
immunity to B. burgdorferi, and chronic neurologic symptoms with no
other identifiable cause. Eight of the patients had been followed
prospectively for 8 to 12 years after the onset of infection.
RESULTS. Of the 27 patients, 24 (89 percent) had a mild
encephalopathy that began 1 month to 14 years after the onset of the
disease and was characterized by memory loss, mood changes, or sleep
disturbance. Of the 24 patients, 14 had memory impairment on
neuropsychological tests, and 18 had increased cerebrospinal fluid
protein levels, evidence of intrathecal production of antibody to B.
burgdorferi, or both. Nineteen of the 27 patients (70 percent) had
polyneuropathy with radicular pain or distal paresthesias; all but
two of these patients also had encephalopathy. In 16 patients
electrophysiologic testing showed an axonal polyneuropathy. One
patient had leukoencephalitis with asymmetric spastic diplegia,
periventricular white-matter lesions, and intrathecal production of
antibody to B. burgdorferi. Among the 27 patients, associated
symptoms included fatigue (74 percent), headache (48 percent),
arthritis (37 percent), and hearing loss (15 percent). At the time of
examination, chronic neurologic abnormalities had been present from 3
months to 14 years, usually with little progression. Six months after
a two-week course of intravenous ceftriaxone (2 g daily), 17 patients
(63 percent) had improvement, 6 (22 percent) had improvement but then
relapsed, and 4 (15 percent) had no change in their condition.
CONCLUSIONS. Months to years after the initial infection with B.
burgdorferi, patients with Lyme disease may have chronic
encephalopathy, polyneuropathy, or less commonly, leukoencephalitis.
These chronic neurologic abnormalities usually improve with
antibiotic therapy.
NLM PUBMED CIT. ID: 2172819 NLM CIT. ID: 91042860
SOURCE:  N Engl J Med 1990 Nov 22;323(21):1438-44
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2172819&form=6&db=m&Dopt=b

TITLE: Bilateral keratitis in Lyme disease.
AUTHORS: Kornmehl EW; Lesser RL; Jaros P; Rocco E; Steere AC
AUTHOR AFFILIATION:
Department of Ophthalmology and Visual Science, Yale University School
of Medicine, New Haven.
ABSTRACT:
Lyme disease, caused by the spirochete Borrelia burgdorferi, has
ophthalmic manifestations. The authors describe two cases of Lyme
keratitis characterized by multiple focal, nebular opacities at
varying levels of the stroma which may progress to edema,
neovascularization, and scarring. Close observation, in addition to
systemic antibiotic therapy, may be sufficient if the visual axis is
not involved, and the patient is asymptomatic.
NLM PUBMED CIT. ID: 2477779 NLM CIT. ID: 90016090
SOURCE:  Ophthalmology 1989 Aug;96(8):1194-7
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2477779&form=6&db=m&Dopt=b

TITLE: Central nervous system manifestations of Lyme disease.
AUTHORS: Pachner AR; Duray P; Steere AC
AUTHOR AFFILIATION:
Department of Neurology, Georgetown University School of Medicine,
Washington, DC.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS RR-00125/RR/NCRR
ABSTRACT:
We studied six patients with central nervous system manifestations of
Lyme disease. Weeks to years after the initial infection, behavioral
changes, ataxia, and/or weakness in bulbar or peripheral muscles
developed. Four of the six patients had a lymphocytic pleocytosis in
the cerebrospinal fluid, and two of them had magnetic resonance
imaging scans suggestive of demyelination. In a patient with a
subacute encephalitis, a brain biopsy specimen showed microgliosis
without an inflammatory infiltrate and spirochetes morphologically
compatible with Borrelia burgdorferi. All six patients had elevated
antibody titers to B burgdorferi in serum, but none had selective
concentration of specific antibody in the cerebrospinal fluid. All
six patients were treated with high-dose intravenous penicillin; four
had complete recoveries and two did not. Lyme disease may affect the
central nervous system causing organic brain disease or syndromes
suggestive of demyelination.
NLM PUBMED CIT. ID: 2742551 NLM CIT. ID: 89301968
SOURCE:  Arch Neurol 1989 Jul;46(7):790-5
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2742551&form=6&db=m&Dopt=b

TITLE: 
A prospective study of tick bites in an endemic area for Lyme disease.
AUTHORS: Costello CM; Steere AC; Pinkerton RE; Feder HM Jr
GRANT/CONTRACT ID:
AR-20358/AR/NIAMS
NO ABSTRACT AVAILABLE.
NLM PUBMED CIT. ID: 2758821 NLM CIT. ID: 89337700
SOURCE:  Conn Med 1989 Jun;53(6):338-40
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2758821&form=6&db=m&Dopt=b

TITLE: Lack of antibodies to Borrelia burgdorferi in patients with
amyotrophic lateral sclerosis [letter]
AUTHORS: Mandell H; Steere AC; Reinhardt BN; Yoshinari N
Munsat TL; Brod SA; Clapshaw PA
NO ABSTRACT AVAILABLE.
NLM PUBMED CIT. ID: 2911315 NLM CIT. ID: 89097141
SOURCE:  N Engl J Med 1989 Jan 26;320(4):255-6
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2911315&form=6&db=m&Dopt=b

TITLE: [A review of Lyme disease]
VERNACULAR TITLE: 
Revisao da borreliose de Lyme.
AUTHORS: Yoshinari NH; Steere AC; Cossermelli W
ABSTRACT:
Lyme disease is an infectious disease caused by the spirochete
Borrelia burgdorferi, transmitted by certain ixodid ticks. The
illness usually occurs in stages with many different clinical
manifestations. The disease starts with a typical cutaneous lesion
called erythema cronicum migrans, that usually develops at the site
of the tick bite. After weeks or months, some patients develop
neurological abnormalities, particularly meningitis, cranial nerve
paralysis, peripheral radiculoneuritis, or cardiac involvement, such
as atrioventricular blockade, myopericarditis and cardiomegaly, or
migratory musculoskeletal pain. Months or years later, many patients
develop arthritis, which usually occurs in intermittent attacks for
several years. Lyme disease was only recently recognized in the
United States. However this borreliosis has now been recognized in
every continent except South America. In this paper we review the
clinical and laboratorial features of Lyme borreliosis and discuss
the possibility of its presence in Brazil or other parts of South
America, where it has recently been recognized that ixodid ticks are
common.
NLM PUBMED CIT. ID: 2690198 NLM CIT. ID: 90099933
SOURCE:  AMB Rev Assoc Med Bras 1989 Jan-Feb;35(1):34-8
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2690198&form=6&db=m&Dopt=b

TITLE: 
A prospective study of tick bites in an endemic area for Lyme disease.
AUTHORS: Costello CM; Steere AC; Pinkerton RE; Feder HM Jr
AUTHOR AFFILIATION:
Middlesex Memorial Hospital, Middletown, Farmington, Connecticut.
GRANT/CONTRACT ID:
AR-20358/AR/NIAMS
NO ABSTRACT AVAILABLE.
NLM PUBMED CIT. ID: 2642519 NLM CIT. ID: 89080336
SOURCE:  J Infect Dis 1989 Jan;159(1):136-9
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2642519&form=6&db=m&Dopt=b

TITLE: 
Lyme borreliosis in the Soviet Union: a cooperative US-USSR report.
AUTHORS: Dekonenko EJ; Steere AC; Berardi VP; Kravchuk LN
AUTHOR AFFILIATION:
Poliomyelitis Institute, Moscow, Union of Soviet Socialist Republics.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS
ABSTRACT:
We identified 90 patients with tick-borne erythema migrans in the
Union of Soviet Socialist Republics (USSR) in areas from the western
Baltic Republics to the Maritime Territory on the Pacific Ocean.
Symptoms associated with the erythema included fever, malaise and
fatigue, headache, myalgias, arthralgias, or regional
lymphadenopathy. Within two weeks to four months, 58 (64%) of the
patients developed neurological abnormalities, particularly radicular
pain, cranial neuritis, or lymphocytic meningitis, and four (4%)
patients developed monoarticular or oligoarticular arthritis. We
tested the sera from 35 Soviet patients by using an isolate from the
United States. The serological data showed elevated IgM and/or IgG
antibody titers to Borrelia burgdorferi in 2 of 10 patients with
erythema migrans, 15 of 21 with neurological abnormalities, and 2 of
4 with arthritis. Our observations suggest that Lyme borreliosis
occurs in diverse areas of the USSR.
NLM PUBMED CIT. ID: 3171226 NLM CIT. ID: 89009980
SOURCE:  J Infect Dis 1988 Oct;158(4):748-53
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3171226&form=6&db=m&Dopt=b

TITLE: 
Serodiagnosis of early Lyme disease: analysis of IgM and IgG antibody
responses by using an antibody-capture enzyme immunoassay.
AUTHORS: Berardi VP; Weeks KE; Steere AC
AUTHOR AFFILIATION:
Department of Virology, Center for Disease Control, Boston,
Massachusetts 02130.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS
ABSTRACT:
We used an antibody-capture enzyme immunoassay (EIA) to evaluate the
early antibody responses to Borrelia burgdorferi in paired sera from
30 patients with erythema chronicum migrans. During acute disease, 20
(67%) patients had elevated specific IgM responses, and by
convalescence (one to four weeks after treatment), 28 (93%) patients
had increased IgM or IgG responses. In acute specimens, elevated IgM
responses correlated with disseminated infection; however, by
convalescence, most patients with either localized or disseminated
disease had positive tests. Among 133 control subjects, IgM cross-
reactivity was observed in 4 of 37 patients with either Epstein-Barr
virus or rickettsial infections, and false-positive IgG tests were
seen in 8 of 28 patients with syphilis. With antibody-capture EIA,
the diagnosis of Lyme disease can be confirmed in the majority of
acutely ill patients and in almost all patients by convalescence.
NLM PUBMED CIT. ID: 3049839 NLM CIT. ID: 89009981
SOURCE:  J Infect Dis 1988 Oct;158(4):754-60
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3049839&form=6&db=m&Dopt=b

TITLE: Anticardiolipin antibodies in Lyme disease.
AUTHORS: Mackworth-Young CG; Harris EN; Steere AC; Rizvi F; 
Malawista SE; Hughes GR; Gharavi AE
AUTHOR AFFILIATION:
Rheumatology Unit, Royal Postgraduate Medical School, Hammersmith
Hospital, London, England.
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-10493/AM/NIADDK 
AM-07107/AM/NIADDK
ABSTRACT:
Sera from 28 patients with Lyme disease were tested for the presence
of anticardiolipin antibodies (ACLA). Seven serum samples had
elevated levels of IgM ACLA, and 4 had elevated levels of IgG ACLA.
Higher IgM ACLA positivity tended to be associated with neurologic
disease, and IgM ACLA levels correlated with the specific IgM
response to the infecting spirochete (P less than 0.01). Absorption
experiments indicated that ACLA and antispirochete antibodies are
largely separate populations. Thus, ACLA may occur in patients with
Lyme disease, particularly in those with neurologic abnormalities,
and the production of these antibodies seems to be linked to the
specific IgM response.
NLM PUBMED CIT. ID: 3408508 NLM CIT. ID: 88309183
SOURCE:  Arthritis Rheum 1988 Aug;31(8):1052-6
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3408508&form=6&db=m&Dopt=b

TITLE: Lyme myositis: muscle invasion by Borrelia burgdorferi.
AUTHORS: Atlas E; Novak SN; Duray PH; Steere AC
AUTHOR AFFILIATION:
Norwalk Hospital, Connecticut.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS
NO ABSTRACT AVAILABLE.
NLM PUBMED CIT. ID: 3389608 NLM CIT. ID: 88267638
SOURCE:  Ann Intern Med 1988 Aug 1;109(3):245-6
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3389608&form=6&db=m&Dopt=b

TITLE: Fatal adult respiratory distress syndrome in a patient with Lyme
disease.
AUTHORS: Kirsch M; Ruben FL; Steere AC; Duray PH; Norden CW; 
Winkelstein A
AUTHOR AFFILIATION:
Department of Medicine, Montefiore Hospital, University of Pittsburgh
School of Medicine, PA 15213.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS
ABSTRACT:
A dry cough, fever, generalized maculopapular rash, and myositis
developed in a 67-year-old woman; she also had markedly abnormal
liver function test results. Serologic tests proved that she had an
infection of recent onset with Borrelia burgdorferi, the agent that
causes Lyme disease. During a two-month course of illness, her
condition remained refractory to treatment with antibiotics,
salicylates, and steroids. Ultimately, fatal adult respiratory
distress syndrome developed; this was believed to be secondary to
Lyme disease.
NLM PUBMED CIT. ID: 3357244 NLM CIT. ID: 88188323
SOURCE:  JAMA 1988 May 13;259(18):2737-9
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3357244&form=6&db=m&Dopt=b

TITLE: 
Comparison of immunoblotting and indirect enzyme-linked immunosorbent
assay using different antigen preparations for diagnosing early Lyme
disease.
AUTHORS: Grodzicki RL; Steere AC
AUTHOR AFFILIATION:
Department of Internal Medicine, Yale University School of Medicine,
New Haven, Connecticut.
GRANT/CONTRACT ID: AR-20358/AR/NIAMS RR-00125/RR/NCRR
ABSTRACT:
We compared immunoblotting and indirect enzyme-linked immunosorbent
assay (ELISA) using different antigen preparations to test for
antibody to Borrelia burgdorferi in patients with early Lyme disease.
With immunoblotting, 16 (53%) of 30 patients had positive tests in
acute- phase sera and 25 (83%) had them in convalescent-phase sera.
Among 64 controls, false-positive results were obtained in only three
individuals with syphilis and in one hospitalized patient with renal
allograft rejection. Among the patients with Lyme disease, both IgM
and IgG antibodies most commonly bound to the 41-kilodalton (kDa)
flagellar antigen, but many patients had binding to other components,
particularly those of 25, 55, 58, or 66 kDa, and the order of their
appearance was variable. Compared with indirect ELISA (using
sonicated whole spirochetes or a flagellin-enriched fraction as the
antigen preparation), more patients with Lyme disease had positive
tests by immunoblotting, and fewer control subjects had
false-positive results. Our results indicate that immunoblotting is
superior to indirect ELISA for diagnosing early Lyme disease.
NLM PUBMED CIT. ID: 3279140 NLM CIT. ID: 88154619
SOURCE:  J Infect Dis 1988 Apr;157(4):790-7
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3279140&form=6&db=m&Dopt=b

TITLE: 
In vivo and in vitro evidence of B cell hyperactivity during Lyme
disease.
AUTHORS: Sigal LH; Steere AC; Dwyer JM
AUTHOR AFFILIATION:
Department of Internal Medicine, Yale University School of Medicine,
Syracuse, NY.
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-5639/AM/NIADDK
RR-00125/RR/NCRR
ABSTRACT:
In vitro IgM production by cells from patients with Lyme disease rose
during the illness in those studied soon after onset, but fell from
elevated levels in those initially studied later than 1 week after
onset. Borrelia burgdorferi stimulated normal and patients' cells
produced IgM, with cells from acutely ill patients producing the
most; production fell during convalescence. Patients with active Lyme
disease and those destined for later manifestations often had serum
agglutinins for heterologous red blood cells. Thus, there is in vitro
and in vivo B cell hyperactivity in Lyme disease caused by B.
burgdorferi. Both mitogenic and antigenic stimulation of B cells may
induce the humoral response seen in complicated Lyme disease.
NLM PUBMED CIT. ID: 3260952 NLM CIT. ID: 88286591
SOURCE:  J Rheumatol 1988 Apr;15(4):648-54
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3260952&form=6&db=m&Dopt=b

TITLE: Experimental Lyme arthritis in rats infected with Borrelia
burgdorferi.
AUTHORS: Barthold SW; Moody KD; Terwilliger GA; Duray PH; 
Jacoby RO; Steere AC
AUTHOR AFFILIATION:
Section of Comparative Medicine, Yale University School of Medicine,
New Haven, Connecticut 06510.
GRANT/CONTRACT ID: RR-00393/RR/NCRR AM-20358/AM/NIADDK
NO ABSTRACT AVAILABLE.
NLM PUBMED CIT. ID: 3258003 NLM CIT. ID: 88154630
SOURCE:  J Infect Dis 1988 Apr;157(4):842-6
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3258003&form=6&db=m&Dopt=b

TITLE: An animal model for Lyme arthritis.
AUTHORS: Barthold SW; Moody KD; Terwilliger GA; Jacoby RO; Steere AC
AUTHOR AFFILIATION:
Section of Comparative Medicine, Yale University School of Medicine,
New Haven, Connecticut 06510.
GRANT/CONTRACT ID: RR00393/RR/NCRR AM20358/AM/NIADDK RR05358/RR/NCRR
ABSTRACT:
A model of Lyme arthritis has been developed in laboratory rats.
Intraperitoneal inoculation of a low-passage tick isolate of B.
burgdorferi into neonatal and weanling LEW/N rats resulted in
multisystemic infection and arthritis. Spirochetes were isolated from
blood, liver, kidney, spleen, brain, and joints of inoculated rats.
Arthritis, associated with the presence of spirochetes, developed in
multiple joints by day 14 and persisted through day 90 after
inoculation. Arthritic lesions resembled those found in human Lyme
disease lesions. Lesions were not found in other organs, although
spirochetes were present. Neonatal F344 and SD rats were also
susceptible to infection and induction of arthritis. Three different
isolates of B. burgdorferi were shown to be pathogenic. Pathogenicity
of one isolate was retained after at least 11 in vitro passages.
Formalin-killed spirochetes were not pathogenic. Other features of
the Lyme disease complex have yet to be seen in the rat, but
long-term studies are required to completely define the rat model.
This highly reproducible model should allow in-depth studies on the
pathogenetic mechanisms of this important human disease.
NLM PUBMED CIT. ID: 3263827 NLM CIT. ID: 89048800
SOURCE:  Ann N Y Acad Sci 1988;539:264-73
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3263827&form=6&db=m&Dopt=b

TITLE: Clinical pathologic correlations of Lyme disease by stage.
AUTHORS: Duray PH; Steere AC
AUTHOR AFFILIATION:
Department of Pathology, Fox Chase Cancer Center, Philadelphia,
Pennsylvania 19111.
ABSTRACT:
Lyme disease is capable of producing a wide variety of clinical
pathologic conditions and lesions having in common histologic
features of collagen-vascular disease. The plasma cell is an
omnipotent inflammatory responder in most tissues involved by Lyme
disease, ranging from relatively acute to lesions that have gone on
for years. Vascular thickening also seems to be prominent, and in the
dermis is accompanied by scleroderma-like collagen expansion. The
disease in some ways resembles the responses seen in lupus
erythematosus such as mild cerebritis with lymphocytes and plasma
cells in the leptomeninges. Lymphoplasmacytic panniculitis of Lyme
disease resembles lupus profundus, both in the infiltrate and the
plasma cell-blood vessel relationship. The onion skin thickened
vessels of the synovia resemble the vessels of lupus spleens, while
the scleradermoid thickening of the dermis and various skin lesions
of stage III Lyme disease suggest a collagen-vascular disorder.
Finally, the perivascular lymphoid infiltrate in clinical myositis
does not differ from that seen in polymyositis or dermatomyositis.
All of these histologic derangements suggest immunologic damage in
response to persistence of the spirochete, however few in number.
NLM PUBMED CIT. ID: 2847622 NLM CIT. ID: 89048814
SOURCE:  Ann N Y Acad Sci 1988;539:65-79
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2847622&form=6&db=m&Dopt=b

TITLE: IgM rheumatoid factor in Lyme disease: correlation with disease
activity, total serum IgM, and IgM antibody to Borrelia burgdorferi.
AUTHORS: Kujala GA; Steere AC; Davis JS 4th
AUTHOR AFFILIATION:
Department of Internal Medicine, University of Virginia School of
Medicine, Charlottesville.
GRANT/CONTRACT ID: 5T32-AM07156/AM/NIADDK AM20358/AM/NIADDK 
AM07107/AM/NIADDK
ABSTRACT:
We tested the sera of 50 patients with Lyme disease for IgM-rheumatoid
factor (IgM-RF) using a sensitive ELISA. Levels of IgM-RF greater
than 3 SD above the mean of normal subjects were found in 2 of 15
patients with erythema chronicum migrans, 7 of 10 with neurologic
abnormalities, and 7 of 25 with Lyme arthritis (p = 0.038). Only 2 of
these sera were positive by latex agglutination. In contrast, none of
the 23 control patients with osteoarthritis, ankylosing spondylitis,
or Reiter's syndrome had positive tests. The levels of IgM-RF
correlated with disease activity (p = 0.002), total serum IgM levels
(p = 0.002), and specific IgM antibody titers to Borrelia burgdorferi
(p = 0.006). IgM- RF reactivity was absorbed with heat aggregated IgG
(HAGG), but the titer of specific IgM antibody was insignificantly
affected by this procedure. Thus, small amounts of RF are produced at
certain times in many patients with Lyme disease, and IgM-RF
production appears to be linked to the specific IgM response.
NLM PUBMED CIT. ID: 3668982 NLM CIT. ID: 88035883
SOURCE:  J Rheumatol 1987 Aug;14(4):772-6
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3668982&form=6&db=m&Dopt=b

TITLE: CNS manifestations of third stage Lyme disease.
AUTHORS: Pachner AR; Steere AC
NO ABSTRACT AVAILABLE.
NLM PUBMED CIT. ID: 3591079 NLM CIT. ID: 87237030
SOURCE:  Zentralbl Bakteriol Mikrobiol Hyg [A] 1987 Feb;263(3):301-6
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3591079&form=6&db=m&Dopt=b

TITLE: 
The spectrum of organ and systems pathology in human Lyme disease.
AUTHORS: Duray PH; Steere AC
ABSTRACT:
Lymphocytes, plasma cells, and mononuclear phagocytes are frequently
found in human tissues infected by the Lyme disease spirochete,
Borrelia burgdorferi. Experience has shown that these cells comprise
the tissue bed inflammatory infiltrate in Lyme disease affecting the
joint synovia, myocardium, and skin. While many differences otherwise
exist, Lyme synovitis has lymphoplasmacellular similarities with
rheumatoid synovitis, lymphoplasmacellular epimyocarditis
similarities with syphilitic myocarditis, and occasionally synovial
endarteritis obliterans. Silver staining can demonstrate the
spirochete if a careful search is done.
NLM PUBMED CIT. ID: 3577479 NLM CIT. ID: 87208536
SOURCE:  Zentralbl Bakteriol Mikrobiol Hyg [A] 1986 Dec;263(1-2):169-78
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3577479&form=6&db=m&Dopt=b

TITLE: 
Ultrastructural differences among spirochetes isolated from patients
with Lyme disease and related disorders, and from Ixodes ricinus.
AUTHORS: Hovind-Hougen K; Asbrink E; Stiernstedt G; Steere AC; Hovmark A
ABSTRACT:
Previous studies on cells of strains B31 isolated in the U.S.A. from
Ixodes dammini and strain G25 isolated in Sweden from Ixodes ricinus,
showed that their ultrastructure was similar, but not identical. For
this reason the studies were extended to spirochetes isolated
directly from patients with Lyme disease and related disorders.
Included in the present study were three strains isolated from skin,
blood and spinal fluid, respectively, from patients with Lyme
disease, two strains from patients with erythema chronicum migrans
and one strain from a patient with acrodermatitis chronica
atrophicans. Three additional strains isolated in Sweden from Ixodes
ricinus were also studied. All spirochetes were examined after
negative straining with 1% ammonium molybdate. The cells of each
individual strain were identical except for one strain isolated from
a tick. This isolate was found to consist of two morphologically
different spirochetes. Comparison of morphological features of cells
from various isolates revealed certain differences. The cells of the
different strains could be divided into at least four groups for
which cell size and shape as well as number of flagella varied. By
morphological criteria, all cells were found to belong to the genus
Borrelia.
NLM PUBMED CIT. ID: 3577472 NLM CIT. ID: 87208523
SOURCE:  Zentralbl Bakteriol Mikrobiol Hyg [A] 1986 Dec;263(1-2):103-11
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3577472&form=6&db=m&Dopt=b

TITLE: Antigens of Borrelia burgdorferi recognized during Lyme disease.
Appearance of a new immunoglobulin M response and expansion of the
immunoglobulin G response late in the illness.
AUTHORS: Craft JE; Fischer DK; Shimamoto GT; Steere AC
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK 
RR-00125/RR/NCRR
ABSTRACT:
Using immunoblots, we identified proteins of Borrelia burgdorferi
bound by IgM and IgG antibodies during Lyme disease. In 12 patients
with early disease alone, both the IgM and IgG responses were
restricted primarily to a 41-kD antigen. This limited response
disappeared within several months. In contrast, among six patients
with prolonged illness, the IgM response to the 41-kD protein
sometimes persisted for months to years, and late in the illness
during arthritis, a new IgM response sometimes developed to a 34-kD
component of the organism. The IgG response in these patients
appeared in a characteristic sequential pattern over months to years
to as many as 11 spirochetal antigens. The appearance of a new IgM
response and the expansion of the IgG response late in the illness,
and the lack of such responses in patients with early disease alone,
suggest that B. burgdorferi remains alive throughout the illness.
NLM PUBMED CIT. ID: 3531237 NLM CIT. ID: 87009051
SOURCE:  J Clin Invest 1986 Oct;78(4):934-9
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3531237&form=6&db=m&Dopt=b

TITLE: 
Newly recognized Leptospira species ("Leptospira inadai" serovar lyme)
isolated from human skin.
AUTHORS: Schmid GP; Steere AC; Kornblatt AN; Kaufmann AF; 
Moss CW; Johnson RC; Hovind-Hougen K; Brenner DJ
ABSTRACT:
Leptospira strain 10, which represents a new Leptospira species, was
isolated from a skin biopsy of a patient with Lyme disease. Although
pathogenic for laboratory animals, the organism was not considered to
have a significant role in the patient's illness.
NLM PUBMED CIT. ID: 3760144 NLM CIT. ID: 87008964
SOURCE:  J Clin Microbiol 1986 Sep;24(3):484-6
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3760144&form=6&db=m&Dopt=b

TITLE: Lyme disease during pregnancy.
AUTHORS: Markowitz LE; Steere AC; Benach JL; Slade JD; Broome CV
ABSTRACT:
Lyme disease is an increasingly recognized tick-borne illness caused
by a spirochete, Borrelia burgdorferi. Because the etiologic agent of
Lyme disease is a spirochete, there has been concern about the effect
of maternal Lyme disease on pregnancy outcome. We reviewed cases of
Lyme disease in pregnant women who were identified before knowledge
of the pregnancy outcomes. Nineteen cases were identified with onset
between 1976 and 1984. Eight of the women were affected during the
first trimester, seven during the second trimester, and two during
the third trimester; in two, the trimester of onset was unknown.
Thirteen received appropriate antibiotic therapy for Lyme disease. Of
the 19 pregnancies, five had adverse outcomes, including syndactyly,
cortical blindness, intrauterine fetal death, prematurity, and rash
in the newborn. Adverse outcomes occurred in cases with infection
during each of the trimesters. Although B burgdorferi could not be
implicated directly in any of the adverse outcomes, the frequency of
such outcomes warrants further surveillance and studies of pregnant
women with Lyme disease.
NLM PUBMED CIT. ID: 2423719 NLM CIT. ID: 86227939
SOURCE:  JAMA 1986 Jun 27;255(24):3394-6
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2423719&form=6&db=m&Dopt=b

TITLE: Proliferative responses of mononuclear cells in Lyme disease.
Reactivity to Borrelia burgdorferi antigens is greater in joint fluid
than in blood.
AUTHORS: Sigal LH; Steere AC; Freeman DH; Dwyer JM
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK 
AI-07174/AI/NIAID
ABSTRACT:
In 27 patients with early Lyme disease, the mean response of
peripheral blood mononuclear cells (PBMC) to Lyme spirochetal
Borrelia burgdorferi antigens (723 counts per minute) was similar to
that of control subjects. During convalescence, 2-3 weeks later, the
patients' mean response was significantly higher (2,075 cpm, P less
than 0.008). Compared with those with early disease, the PBMC of 22
patients with Lyme arthritis reacted even more to B burgdorferi
(2,923 cpm, P less than 0.0004), and, by far, the greatest response
was in concomitantly obtained synovial fluid mononuclear cells
(15,238 cpm, P less than 0.001). The PBMC of patients with early Lyme
disease reacted slightly less to phytohemagglutinin and pokeweed
mitogen than those of normal control subjects, but patients with
arthritis had greater than normal mitogen responses. In contrast,
mitogen reactivity among synovial fluid cells was markedly decreased
and correlated inversely with the response to antigen. Thus, in
patients with Lyme disease, the antigen-specific responses of
mononuclear cells increase as the disease progresses, and in those
with arthritis, the greatest reactivity to antigen is found in cells
in the inflamed joint.
NLM PUBMED CIT. ID: 2941022 NLM CIT. ID: 86242356
SOURCE:  Arthritis Rheum 1986 Jun;29(6):761-9
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2941022&form=6&db=m&Dopt=b

TITLE: Lyme disease: infectious in origin, rheumatic in expression.
AUTHORS: Malawista SE; Steere AC
GRANT/CONTRACT ID: AM20358/AM/NIADDK AM07107/AM/NIADDK
NO ABSTRACT AVAILABLE.
NLM PUBMED CIT. ID: 3511614 NLM CIT. ID: 86126385
SOURCE:  Adv Intern Med 1986;31:147-66
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3511614&form=6&db=m&Dopt=b

TITLE: Facial paralysis in Lyme disease.
AUTHORS: Clark JR; Carlson RD; Sasaki CT; Pachner AR; Steere AC
ABSTRACT:
Lyme disease is a multisystemic illness caused by a tick-borne
spirochete. Once considered unique to the Connecticut coastline,
thousands of cases are now documented throughout the United States,
northern Europe, and Australia. Unilateral and bilateral facial
paralysis may occur in up to 11% of patients with Lyme disease. This
paper reviews the clinical course, distinguishing features, and
outcome of 124 such palsies in 101 patients seen between 1975 and
1984. The 99.2% spontaneous recovery rate demonstrates the
unequivocally excellent prognosis of this palsy and confirms that
operative intervention is not indicated. The otolaryngologist should
consider this etiology in all otherwise idiopathic facial paralyses,
especially when presenting in summer months in endemic areas, or when
bilateral. Positive Lyme disease spirochete titers are helpful in the
diagnosis. We believe antibiotics should be given to patients with
this facial palsy in order to treat any other concurrent
manifestations of the illness and to prevent subsequent
complications.
NLM PUBMED CIT. ID: 4058212 NLM CIT. ID: 86039510
SOURCE:  Laryngoscope 1985 Nov;95(11):1341-5
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=4058212&form=6&db=m&Dopt=b

TITLE: 
Antigen-specific proliferation of CSF lymphocytes in Lyme disease.
AUTHORS: Pachner AR; Steere AC; Sigal LH; Johnson CJ
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK 
AI-07174/AI/NIAID
ABSTRACT:
The neurologic manifestations of Lyme disease include meningitis,
radiculoneuritis, and cranial neuritis. In two patients, we
investigated the proliferative response of CSF and peripheral blood
lymphocytes to protein antigens derived from the Lyme disease
spirochete. The response of CSF lymphocytes was 5 to 10 times greater
than that of peripheral blood lymphocytes. In contrast, in the one
patient studied, lectin-induced proliferation was less in CSF than in
peripheral blood. These findings show that the CSF of patients with
Lyme meningitis is an enriched source of antigen-specific
proliferative lymphocytes.
NLM PUBMED CIT. ID: 2414686 NLM CIT. ID: 86040836
SOURCE:  Neurology 1985 Nov;35(11):1642-4
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2414686&form=6&db=m&Dopt=b

TITLE: Fatal pancarditis in a patient with coexistent Lyme disease and
babesiosis. Demonstration of spirochetes in the myocardium.
AUTHORS: Marcus LC; Steere AC; Duray PH; Anderson AE; Mahoney EB
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK 
RR-00125/RR/NCRR
ABSTRACT:
A 66-year-old man developed fever, chills, myalgias, three
erythematous skin lesions, and transient left eyelid lag. Because of
persistent fever, he was hospitalized 4 weeks after the onset of
disease; a peripheral blood smear showed Babesia microti in 3% of his
erythrocytes. Eighteen hours later, he died unexpectedly. Autopsy
showed pancarditis with a diffuse lymphoplasmacytic infiltrate, and
spirochetes were found in the myocardium. Antibody titers to both the
Lyme disease spirochete Borrelia burgdorferi and Babesia microti were
elevated. The finding of spirochetes in the myocardium and the
elevated antibody titers to Borrelia burgdorferi suggest that the
patient died from cardiac involvement of Lyme disease.
NLM PUBMED CIT. ID: 4040723 NLM CIT. ID: 85277664
SOURCE:  Ann Intern Med 1985 Sep;103(3):374-6
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=4040723&form=6&db=m&Dopt=b

TITLE: 
Maternal-fetal transmission of the Lyme disease spirochete, Borrelia
burgdorferi.
AUTHORS: Schlesinger PA; Duray PH; Burke BA; Steere AC; Stillman MT
GRANT/CONTRACT ID: AM-20358/AM/NIADDK
NO ABSTRACT AVAILABLE.
NLM PUBMED CIT. ID: 4003991 NLM CIT. ID: 85223525
SOURCE:  Ann Intern Med 1985 Jul;103(1):67-8
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=4003991&form=6&db=m&Dopt=b

TITLE: Surveillance of Lyme disease in the United States, 1982.
AUTHORS: Schmid GP; Horsley R; Steere AC; Hanrahan JP; Davis JP; 
Bowen GS; Osterholm MT; Weisfeld JS; Hightower AW; Broome CV
ABSTRACT:
Lyme disease is a tick-borne illness that has been reported from three
regions in the United States--the Northeast, Midwest, and West--which
correspond to the distribution of the recognized vectors of the
disease, Ixodes dammini and Ixodes pacificus. In 1982, a surveillance
system designed to define the morbidity and geographic distribution
for Lyme disease by using a clinical case definition received
information on 491 definite cases and 38 probable cases. Of the
definite cases, 489 were acquired in endemic areas of the Northeast
or Midwest; one case was acquired in Utah and one in western
Pennsylvania, two areas where the illness had not been previously
reported. Three states that previously had not reported cases of Lyme
disease (Kentucky, Indiana, Montana) reported probable cases. In 37%
of the definite cases, the patients had neurological symptoms (most
commonly reported was headache with stiff neck, suggestive of
meningitis), 10% cardiac symptoms (most commonly reported was
palpitations), and 54% arthritic symptoms (most commonly reported in
large joints). The occurrence of Lyme disease in areas outside the
currently recognized endemic regions, as well as the recent
description of Amblyomma americanum as a probable vector, suggest
that additional vectors may be described in the future.
NLM PUBMED CIT. ID: 3998509 NLM CIT. ID: 85209375
SOURCE:  J Infect Dis 1985 Jun;151(6):1144-9
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3998509&form=6&db=m&Dopt=b

TITLE: Arthritis caused by Borrelia burgdorferi in dogs.
AUTHORS: Kornblatt AN; Urband PH; Steere AC
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK 
AM-5639/AM/NIADDK
ABSTRACT:
From October 1982 to May 1984, we studied 34 dogs from the Lyme, Conn
area that had a history of tick exposure and lameness associated with
pain, warmth, and/or swelling in one or more joints. Large numbers of
polymorphonuclear leukocytes were seen in Giemsa-stained smears of
synovial fluid from 9 dogs, and spirochetes (Borrelia burgdorferi)
were found in 1 sample by darkfield microscopy and immunoperoxidase
techniques. The geometric mean antibody titer to B burgdorferi in the
34 dogs was 1:2,700, compared with 1:285 in 43 clinically normal dogs
from the same area (P less than 0.0001) and 1:50 in 29 dogs from an
area in New Jersey that is not endemic for human Lyme disease (P less
than 0.00001). We concluded that B burgdorferi in dogs may cause
arthritis similar to that in human Lyme disease.
NLM PUBMED CIT. ID: 3997648 NLM CIT. ID: 85207183
SOURCE:  J Am Vet Med Assoc 1985 May 1;186(9):960-4
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3997648&form=6&db=m&Dopt=b

TITLE: Diagnosing early Lyme disease.
AUTHORS: Shrestha M; Grodzicki RL; Steere AC
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK 
RR-00125/RR/NCRR
ABSTRACT:
The diagnostic value of clinical, culture, and serologic findings was
studied prospectively in 41 patients with early Lyme disease. Fifteen
patients had erythema chronicum migrans alone, and 26 had clinical
evidence of disseminated infection, most commonly affecting the brain
or meninges, other skin sites, lymph nodes, or joints. Of 40 blood
cultures, only one, from a patient with disseminated infection,
yielded spirochetes. One of 10 patients tested with localized
infection had an elevated IgM response to the Lyme spirochete (200
units or greater) during acute disease. Two to three weeks after
beginning antibiotic therapy, four of the 10 patients had elevated
specific IgM or IgG responses (200 units or greater). Of the 22
patients tested with disseminated disease, 10 initially had elevated
levels of specific IgM or IgG, and 12 had such responses by
convalescence. Because of the low yield of cultures and the delay in
the specific antibody response, recognition of the clinical picture
remains very important in diagnosing early Lyme disease.
NLM PUBMED CIT. ID: 3970049 NLM CIT. ID: 85119303
SOURCE:  Am J Med 1985 Feb;78(2):235-40
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3970049&form=6&db=m&Dopt=b

TITLE: Lyme arthritis. Spirochetes found in synovial microangiopathic
lesions.
AUTHORS: Johnston YE; Duray PH; Steere AC; Kashgarian M; 
Buza J; Malawista SE; Askenase PW
PUBLICATION TYPES:
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK 
RR-00125/RR/NCRR
ABSTRACT:
In 17 patients with Lyme disease, synovial specimens, obtained by
synovectomy or needle biopsy, showed nonspecific villous hypertrophy,
synovial cell hyperplasia, prominent microvasculature,
lymphoplasmacellular infiltration, and sometimes lymphoid follicles.
The larger surgically obtained specimens also showed striking
deposition of fibrin in synovial stroma and a form of endarteritis
obliterans. In 2 patients, spirochetes were seen in and around blood
vessels by the Dieterle silver stain. Compared with 55 cases of other
synovial disease, obliterative microvascular lesions were seen only
in Lyme synovia, but marked stromal deposition of fibrin seemed
nonspecific. These findings imply that the Lyme spirochete may
survive for years in affected synovium and may be directly
responsible for the microvascular injury.
NLM PUBMED CIT. ID: 3966535 NLM CIT. ID: 85094500
SOURCE:  Am J Pathol 1985 Jan;118(1):26-34
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3966535&form=6&db=m&Dopt=b

TITLE: 
The triad of neurologic manifestations of Lyme disease: meningitis,
cranial neuritis, and radiculoneuritis.
AUTHORS: Pachner AR; Steere AC
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK 
AI-07174/AI/NIAID
ABSTRACT:
We studied 38 patients with Lyme meningitis, a newly recognized
spirochetal infection. The patients characteristically had
intermittent attacks of severe headache, mild meningismus, and a
predominantly lymphocytic pleocytosis. In addition to meningitis, 11
patients experienced subtle encephalitic signs, 19 had cranial
neuritis, most commonly unilateral or bilateral facial palsy, and 12
developed peripheral radiculoneuritis, plexitis, or mononeuritis
multiplex. Without antibiotic therapy, the duration of neurologic
involvement was 3 to 18 months. Although sometimes incomplete, the
triad of neurologic manifestations of Lyme disease--meningitis,
cranial neuritis, and radiculoneuritis--presents a unique clinical
picture.
NLM PUBMED CIT. ID: 3966001 NLM CIT. ID: 85086774
SOURCE:  Neurology 1985 Jan;35(1):47-53
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3966001&form=6&db=m&Dopt=b

TITLE: Lyme arthritis: radiologic findings.
AUTHORS: Lawson JP; Steere AC
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK
AI-07174/AI/NIAID
ABSTRACT:
Lyme disease is a newly recognized, multi-system disorder that may be
associated with chronic arthritis. Of 25 patients with severe
arthritic manifestations the most frequent radiographic finding was
knee joint effusion. Intra-articular edema was often accompanied by a
continuum of soft-tissue changes involving the infrapatellar fat pad,
periarticular soft tissues, and the entheses, which were sometimes
thickened, calcified, or ossified. Later in the illness, the joints
of some patients showed typical changes of an inflammatory arthritis,
including juxta-articular osteoporosis, cartilage loss, and cortical
or marginal bone erosions. Less commonly, other patients demonstrated
changes more characteristic of degenerative arthritis, including
cartilage loss, subarticular sclerosis, and osteophytosis. Joint
involvement of Lyme disease has similarities to juvenile arthritis
and Reiter syndrome, but can usually be distinguished clinically and
serologically from these entities.
NLM PUBMED CIT. ID: 3964949 NLM CIT. ID: 85064588
SOURCE:  Radiology 1985 Jan;154(1):37-43
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3964949&form=6&db=m&Dopt=b

TITLE: 
Experimental Lyme disease in rabbits: spirochetes found in erythema
migrans and blood.
AUTHORS: Kornblatt AN; Steere AC; Brownstein DG
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK 
AM-5639/AM/NIADDK
ABSTRACT:
In attempts to produce experimental Lyme disease, 33 rabbits were
inoculated with Lyme spirochetes by tick feeding or from tick organ
homogenates or cultures. Two rabbits developed erythema chronicum
migrans at the site of inoculation, in one instance 2 days after
injection of a tick organ homogenate and in the other instance, 17
days after feeding of infected Ixodes dammini ticks. Spirochetes were
seen in skin biopsy specimens of the second lesion with
Warthin-Starry and immunoperoxidase stains. Spirochetes were also
recovered from blood cultures of two additional rabbits 2 weeks
post-inoculation. These findings are characteristic of early Lyme
disease in humans and give additional support for the spirochetal
etiology of Lyme disease.
NLM PUBMED CIT. ID: 6480108 NLM CIT. ID: 85005669
SOURCE:  Infect Immun 1984 Oct;46(1):220-3
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6480108&form=6&db=m&Dopt=b

TITLE: 
Cellular immune findings in Lyme disease. Correlation with serum IgM
and disease activity.
AUTHORS: Moffat CM; Sigal LH; Steere AC; Freeman DH; Dwyer JM
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK
AI-07174/AI/NIAID
ABSTRACT:
Cellular immune findings were studied in 48 patients with various
stages of Lyme disease. At each stage, some patients, particularly
those with neuritis or carditis, had elevated serum IgM levels and
lymphopenia. During early disease, mononuclear cells tended to
respond normally to phytohemagglutinin, and spontaneous suppressor
cell activity was greater than normal. Later, during active neuritis,
carditis, or arthritis, the trend was toward heightened
phytohemagglutinin responsiveness and less suppression than normal.
By multiple regression analysis, serum IgM levels correlated directly
with disease activity (p = 0.025) and inversely with the number of T
cells (p = 0.02); during acute disease only, elevated IgM levels
correlated with increased phytohemagglutinin responsiveness (p =
0.004) and decreased suppressor cell activity (p = 0.03). Decreased
suppression, observed later in the disease, may permit damage to host
tissues because of either autoimmune phenomena or a heightened
response to the Lyme spirochete.
NLM PUBMED CIT. ID: 6237576 NLM CIT. ID: 85020113
SOURCE:  Am J Med 1984 Oct;77(4):625-32
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6237576&form=6&db=m&Dopt=b

TITLE: DNA characterization of the spirochete that causes Lyme disease.
AUTHORS: Schmid GP; Steigerwalt AG; Johnson SE; Barbour AG; Steere AC; 
Robinson IM; Brenner DJ
ABSTRACT:
Lyme disease, a tick-borne disease long recognized in Europe but only
recently recognized in the United States, was shown in 1982-1983 to
be caused by a spirochete, the Lyme disease spirochete. Whether one
or more species of the spirochete exists is unknown, as is its
taxonomic status. To answer these questions, we determined (i) the
DNA base (guanidine-plus-cytosine) content for five strains; (ii) the
DNA relatedness of 10 strains from Europe or the United States
(isolated from ticks, humans, and a mouse) by DNA hybridization
(hydroxyapatite assay at 50 and 65 degrees C); and (iii) the DNA
relatedness to other pathogenic spirochetes. The
guanine-plus-cytosine content of the Lyme disease spirochete strains
was 27.5 to 29.0 mol%, most similar to those of Borrelia hermsii
(30.6 mol%) and Treponema hyodysenteriae (25.6 mol%) among the other
spirochetes tested. DNA hybridization studies with 32P-labeled DNA
from Lyme disease spirochete strain TLO-005, a human blood isolate,
revealed divergence (unpaired bases) within related nucleotide
sequences of only 0.0 to 1.0% for all nine Lyme disease spirochete
strains tested for relatedness to TLO-005. Relatedness values of
seven strains to TLO-005 were 58 to 98% (mean, 71%) in 50 degrees C
reactions and 50 to 93% (mean, 69%) in 65 degrees C reactions. Two
other strains, from which very low yields of DNA were obtained,
showed less relatedness (36 to 50 degrees C, 38 to 47% at 65 degrees
C).(ABSTRACT TRUNCATED AT 250 WORDS)
NLM PUBMED CIT. ID: 6490812 NLM CIT. ID: 85030824
SOURCE:  J Clin Microbiol 1984 Aug;20(2):155-8
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6490812&form=6&db=m&Dopt=b

TITLE: DNA characterization of Lyme disease spirochetes.
AUTHORS: Schmid GP; Steigerwalt AG; Johnson S; Barbour AG; Steere AC; 
Robinson IM; Brenner DJ
ABSTRACT:
Lyme disease spirochetes (LDS) have phenotypic characteristics of both
treponemes and borreliae. To ascertain whether one or more species of
LDS exist, as well as their taxonomic status, we determined the DNA
base (G + C) content for three strains of LDS, the DNA relatedness of
ten strains isolated in the United States or Europe, and the DNA
relatedness of LDS to other spirochetes. The G + C content of the
three LDS strains was 28.1-29.0 mol%, most similar to those of
Borellia hermsii (30.6 mol %) and Treponema hyodysenteriae (25.6 mol
%) among the other spirochetes tested. DNA hybridization studies of
nine LDS strains to a reference strain isolated from human blood
revealed divergence (unpaired bases) within related nucleotide
sequences of only 0.0-1.0 percent, indicating the strains were one
species. Similarly, relatedness values of seven strains to the
reference strain were high: 58-98 percent (mean, 71 percent) in 50
degrees C reactions and 50-93 percent (mean, 69 percent) in 65
degrees C reactions. Labeled DNA from B. hermsii was 30-40 percent
related to three Lyme disease spirochete strains in 50 degrees C
reactions and 8-10 percent related in 65 degrees C reactions. In
contrast, DNA from the reference LDS strain showed relatedness of
only 1 percent to DNAs of two leptospires and only 16 percent to DNA
from T. hyodysenteriae. We conclude that LDS are a single species,
genetically unlike treponemes or leptospires, which belong in the
genus Borrelia.
NLM PUBMED CIT. ID: 6516455 NLM CIT. ID: 85092783
SOURCE:  Yale J Biol Med 1984 Jul-Aug;57(4):539-42
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6516455&form=6&db=m&Dopt=b

TITLE: Neurological findings of Lyme disease.
AUTHORS: Pachner AR; Steere AC
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK A1-07174
ABSTRACT:
Neurologic involvement of Lyme disease typically consists of
meningitis, cranial neuropathy, and radiculoneuritis, alone or in
combination, lasting for months. From 1976 to 1983, we studied 38
patients with Lyme meningitis. Headache and mild neck stiffness,
which fluctuated in intensity, and lymphocytic pleocytosis were the
common findings. Half of the patients also had facial palsies, which
were unilateral in 12 and bilateral in seven. In addition, 12
patients had motor and/or sensory radiculoneuropathies; asymmetric
weakness of extremities was the most common finding. Although
incomplete presentations of neurologic involvement of Lyme disease
may be confused with other entities, the typical constellation of
neurologic symptoms represents a unique clinical picture.
NLM PUBMED CIT. ID: 6516450 NLM CIT. ID: 85092775
SOURCE:  Yale J Biol Med 1984 Jul-Aug;57(4):481-3
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6516450&form=6&db=m&Dopt=b

TITLE: Lyme disease: a unique human model for an infectious etiology of
rheumatic disease.
AUTHORS: Malawista SE; Steere AC; Hardin JA
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-10493/AM/NIADDK 
AM-07107/AM/NIADDK
ABSTRACT:
Lyme disease is a complex immune-mediated multi-system disorder that
is infectious in origin and inflammatory or "rheumatic" in
expression. Through its epidemiologic characteristics, large numbers
of a seasonally synchronized patient population are readily available
for prospective study. Lyme disease has a known clinical onset ("zero
time"), marked by the characteristic expanding skin lesion, erythema
chronicum migrans, and a clearly defined pre-articular phase. At
least some manifestations of the disorder are responsive to
antibiotics, and the causative agent--a spirochete--is now known.
These advantages make Lyme disease unique as a human model for an
infectious etiology of rheumatic disease.
NLM PUBMED CIT. ID: 6516449 NLM CIT. ID: 85092774
SOURCE:  Yale J Biol Med 1984 Jul-Aug;57(4):473-7
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6516449&form=6&db=m&Dopt=b

TITLE: Infection in rabbits with the Lyme disease spirochete.
AUTHORS: Kornblatt AN; Steere AC; Brownstein DG
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK 
AM-5639/AM/NIADDK
ABSTRACT:
Of 33 rabbits inoculated with Lyme disease spirochetes, two developed
erythema chronicum migrans at the site of inoculation. Spirochetes
were seen in skin biopsies of one of the lesions with
immunoperoxidase and Warthin-Starry stains. Spirochetes were also
recovered from the blood of two additional rabbits two weeks
post-inoculation. These findings are characteristic of early Lyme
disease in humans.
NLM PUBMED CIT. ID: 6393613 NLM CIT. ID: 85092795
SOURCE:  Yale J Biol Med 1984 Jul-Aug;57(4):613-6
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6393613&form=6&db=m&Dopt=b

TITLE: 
Ixodes ricinus spirochete and European erythema chronicum migrans
disease.
AUTHORS: Ackermann R; Kabatzki J; Boisten HP; Steere AC; 
Grodzicki RL; Hartung S; Runne U
ABSTRACT:
From three endemic locations of erythema chronicum migrans disease in
North Rhine-Westphalia, Germany, we recovered 19 isolates of a
spirochete from Ixodes ricinus ticks. The infection rate in adult
ticks was 16 percent. The isolated spirochete is immunologically
related to the Ixodes dammini spirochete, Borrelia duttoni, and
Treponema pallidum. Using indirect immunofluorescence, the sera of 90
patients with erythema chronicum migrans disease showed antibody
titers against the isolated spirochete, which correlated with the
clinical course. Similarly, antibodies were demonstrated in the sera
of 21 patients with acrodermatitis chronica atrophicans. These
results suggest an etiologic role for the Ixodes ricinus spriochete
in European erythema chronicum migrans disease.
NLM PUBMED CIT. ID: 6393609 NLM CIT. ID: 85092789
SOURCE:  Yale J Biol Med 1984 Jul-Aug;57(4):573-80
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6393609&form=6&db=m&Dopt=b

TITLE: The antibody response in Lyme disease.
AUTHORS: Craft JE; Grodzicki RL; Shrestha M; Fischer DK; 
Garcia-Blanco M; Steere AC
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK 
AM-5639/AM/NIADDK
ABSTRACT:
We determined the antibody response against the Ixodes dammini
spirochete in Lyme disease patients by indirect immunofluorescence
and an enzyme-linked immunosorbent assay (ELISA). The specific IgM
response became maximal three to six weeks after disease onset, and
then declined, although titers sometimes remained elevated during
later disease. Specific IgM levels correlated directly with total
serum IgM. The specific IgG response, often delayed initially, was
nearly always present during neuritis and arthritis, and frequently
remained elevated after months of remission. Although results
obtained by indirect immunofluorescence and the ELISA were similar,
the ELISA was more sensitive and specific. Cross-reactive antibodies
from patients with other spirochetal infections were blocked by
absorption of sera with Borrelia hermsii, but titers of Lyme disease
sera were also decreased. To further characterize the specificity of
the humoral immune response against the I. dammini spirochete,
35S-methionine-labeled spirochetal antigens were identified by
immunoprecipitation with sera from Lyme arthritis patients. These
polypeptides had molecular weights of 62, 60, 47, 37, 22, 18, and 15
kDa, and were not recognized by control sera. We conclude that the
ELISA, without absorption, is the best method to assay the humoral
immune response in Lyme disease, and we have identified
methionine-containing spirochetal polypeptides that may be important
in Lyme arthritis.
NLM PUBMED CIT. ID: 6393607 NLM CIT. ID: 85092787
SOURCE:  Yale J Biol Med 1984 Jul-Aug;57(4):561-5
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6393607&form=6&db=m&Dopt=b

TITLE: The pathogenesis of arthritis in Lyme disease: humoral immune
responses and the role of intra-articular immune complexes.
AUTHORS: Hardin JA; Steere AC; Malawista SE
ABSTRACT:
We studied 78 patients with Lyme disease to determine how immune
complexes and autoantibodies are related to the development of
chronic Lyme arthritis. Circulating C1q binding material was found in
nearly all patients at onset of erythema chronicum migrans, the skin
lesion that marks the onset of infection with the causative
spirochete. In patients with only subsequent arthritis this material
tended to localize to joints where it gradually increased in
concentrations with greater duration of joint inflammation. In
joints, its concentration correlated positively with the number of
synovial fluid polymorphonuclear leukocytes. Despite the prolonged
presence of putative immune complexes, rheumatoid factors could not
be demonstrated. These observations suggest that phlogistic immune
complexes based on spirochete antigens form locally within joints
during chronic Lyme arthritis.
NLM PUBMED CIT. ID: 6334939 NLM CIT. ID: 85092791
SOURCE:  Yale J Biol Med 1984 Jul-Aug;57(4):589-93
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6334939&form=6&db=m&Dopt=b

TITLE: Cellular immune findings in Lyme disease.
AUTHORS: Sigal LH; Moffat CM; Steere AC; Dwyer JM
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK 
AI-07174/AI/NIAID
ABSTRACT:
From 1981 through 1983, we did the first testing of cellular immunity
in Lyme disease. Active established Lyme disease was often associated
with lymphopenia, less spontaneous suppressor cell activity than
normal, and a heightened response of lymphocytes to
phytohemagglutinin and Lyme spirochetal antigens. Thus, a major
feature of the immune response during active disease seems to be a
lessening of suppression, but it is not yet known whether this
response plays a role in the pathophysiology of the disease.
NLM PUBMED CIT. ID: 6240164 NLM CIT. ID: 85092792
SOURCE:  Yale J Biol Med 1984 Jul-Aug;57(4):595-8
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6240164&form=6&db=m&Dopt=b

TITLE: 
Antibody response in Lyme disease: evaluation of diagnostic tests.
AUTHORS: Craft JE; Grodzicki RL; Steere AC
GRANT/CONTRACT ID: AM-20358/AM/NIADDK AM-07107/AM/NIADDK 
AM-5639/AM/NIADDK
ABSTRACT:
The antibody response to the Ixodes dammini spirochete was determined
in 41 serial serum samples from 12 patients with Lyme disease. By
enzyme-linked immunosorbent assay (ELISA), 11 of the 12 patients had
higher titers of specific IgM antibody (greater than 1:200) during
early disease than did 40 control subjects. Specific IgM antibody
titers, which correlated with total amounts of IgM antibody (P less
than .001), sometimes remained elevated throughout the illness.
During neuritis, nine of 10 patients had higher specific IgG antibody
titers (greater than 1:200) than did controls, and when arthritis was
present, all had such titers, which remained elevated after months of
remission. In the ELISA, antibody responses determined by single or
serial dilutions were similar, but the ELISA was more sensitive and
specific than was immunofluorescence. Adsorption of sera with
Borrelia hermsii generally resulted in a fourfold decrease in titers
of cross-reactive antibodies, but the titers of sera from patients
with Lyme disease were also reduced. Currently, the ELISA, without
adsorption, is the best diagnostic test for Lyme disease.
NLM PUBMED CIT. ID: 6373966 NLM CIT. ID: 84214325
SOURCE:  J Infect Dis 1984 May;149(5):789-95
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6373966&form=6&db=m&Dopt=b

TITLE: [Spirochete etiology of erythema chronicum migrans disease]
VERNACULAR TITLE: 
Spirochaten-Atiologie der Erythema-chronicum-migrans-Krankheit.
AUTHORS: Ackermann R; Kabatzki J; Boisten HP; Steere AC; 
Grodzicki RL; Hartung S; Runne U
GRANT/CONTRACT ID: AM-20358/AM/NIADDK
ABSTRACT:
From ticks of the type Ixodes ricinus, 19 strains of a spirochete were
isolated at three places of infection of erythema chronicum migrans
disease. The spirochete was immunologically related to Borrelia
duttoni, Treponema pallidum and Ixodes dammini spirochete, the
causative organism of North American erythema chronicum migrans
disease (Lyme disease). The isolated spirochete differed from the
North American one in its reaction with monoclonal antibodies and
possibly in its electronmicroscopic structure. A corresponding
spirochete was isolated from the blood of a woman with erythema
chronicum migrans. Of 39 patients with erythema chronicum migrans
mostly treated with antibiotics 50% had increased IgG antibody titre
(1:64 to 1:1024) against the isolated spirochete, while among 51
untreated patients with tick-transmitted meningopolyneuritis 90% had
increased IgG antibody titres. Fourfold antibody titres increases or
falls were found on 50 occasions. IgG antibody titres up to 1:64 were
demonstrated also in CSF, in 22 instances with significant changes.
Increased serum IgM antibody titres of 1:32 to 1:256 were observed in
20% and 68%, respectively, of patients. These findings suggest that
the isolated spirochete is the causative agent of erythema chronicum
migrans disease in Europe. Its antigen structure and arrangement is
similar to that of the causative agent of Lyme disease.
NLM PUBMED CIT. ID: 6363033 NLM CIT. ID: 84108115
SOURCE:  Dtsch Med Wochenschr 1984 Jan 20;109(3):92-7
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6363033&form=6&db=m&Dopt=b

TITLE: 
Antibodies of patients with Lyme disease to components of the Ixodes
dammini spirochete.
AUTHORS: Barbour AG; Burgdorfer W; Grunwaldt E; Steere AC
ABSTRACT:
Lyme disease is an inflammatory disorder of skin, joints, nervous
system, and heart. The disease is associated with a preceding tick
bite and is ameliorated by penicillin treatment. A spirochete (IDS)
isolated from Ixodes dammini ticks has been implicated as the
etiologic agent of Lyme disease. We examined the antibody responses
of Lyme disease patients to IDS lysate components in order to further
understand the pathogenesis of this disease. The components were
separated by sodium dodecyl sulfate-polyacrylamide gel
electrophoresis, transferred to nitrocellulose, reacted with
patients' sera, and the bound IgG was detected with 125I-labeled
protein A (western blot). We found that (a) Lyme disease patients had
antibodies to IDS components (b) most patients studied had antibodies
to two components with apparent subunit molecular weights of 41,000
and 60,000, and (c) the patients' antibody responses during illness
and remission were specific, for the most part, for the IDS. In
contrast to the findings with Lyme disease sera, sera from controls
showed little reactivity with IDS components in either the western
blots or a derivative solid-phase radioimmunoassay.
NLM PUBMED CIT. ID: 6348092 NLM CIT. ID: 83266214
SOURCE:  J Clin Invest 1983 Aug;72(2):504-15
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6348092&form=6&db=m&Dopt=b

TITLE: 
Immune complexes and the evolution of Lyme arthritis. Dissemination
and localization of abnormal C1q binding activity.
AUTHORS: Hardin JA; Steere AC; Malawista SE
ABSTRACT:
In a prospective study of 78 patients with Lyme arthritis, abnormal
serum C1q binding activity was present at the initial onset of
erythema chronicum migrans in nearly all cases. The abnormal binding
persisted in patients with subsequent nerve or heart involvement. In
contrast, among those with only subsequent arthritis, it usually
disappeared within three months (P = 0.018). However, in the synovial
fluid of affected joints, abnormal binding was uniformly present, and
always to a greater extent than in the circulation. The abnormally
reactive material behaved like antigen-antibody complexes. It had a
density of 19S or greater, dissociated below pH 4.2, and lacked
antiglobulin activity. Cryoprecipitates containing immunoglobulin
were good but insensitive predictors of its presence, but immune
complexes themselves did not seem primarily responsible for
cryoprecipitability. Thus, as judged by C1q binding, immune complexes
remain disseminated in certain patients with Lyme arthritis but
localize to joints in others.
NLM PUBMED CIT. ID: 503166 NLM CIT. ID: 80054658
SOURCE:  N Engl J Med 1979 Dec 20;301(25):1358-63
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=503166&form=6&db=m&Dopt=b

TITLE: Neurologic abnormalities of Lyme disease.
AUTHORS: Reik L; Steere AC; Bartenhagen NH; Shope RE; Malawista SE
NO ABSTRACT AVAILABLE.
NLM PUBMED CIT. ID: 449663 NLM CIT. ID: 79198890
SOURCE:  Medicine (Baltimore) 1979 Jul;58(4):281-94
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=449663&form=6&db=m&Dopt=b

TITLE: 
Circulating immune complexes in Lyme arthritis. Detection by the 125I-
C1q binding, C1q solid phase, and Raji cell assays.
AUTHORS: Hardin JA; Walker LC; Steere AC; Trumble TC; Tung KS; 
Williams RC Jr; Ruddy S; Malawista SE
NO ABSTRACT AVAILABLE.
NLM PUBMED CIT. ID: 429566 NLM CIT. ID: 79151567
SOURCE:  J Clin Invest 1979 Mar;63(3):468-77
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=429566&form=6&db=m&Dopt=b

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Compiled by
Art Doherty
Lompoc, California
doherty@utech.net