PLATELET AND NEUTROPHIL ANTIGENS GENOTYPING

Introduction:

 Alloimmunization against human platelet antigens (HPAs) and human neutrophil antigens (HNAs) plays a major role in alloimmune thrombocytopenia and alloimmune neutropenia, respectively. There are essentially three clinical conditions caused by platelet-specific alloantibodies against HPAS: neonatal alloimmune thrombocytopenia, post transfusion purpura, and platelet transfusion refractoriness. In addition, two rare alloimmune thrombocytopenic syndromes are known; passive alloimmune thrombocytopenia and transplantation-associated thrombocytopenia.

                      Currently, five HPA systems (HPA-1 to –5) and eight low-frequency alloantigens (HPA-6bW to –13bW) have been described. The alloantigenic determinants of HPAs were localized on platelet membrane glycoproteins (GP)Ia, Iba, Ibb, IIb and IIIa. All of these have been found to result from point mutations in the encoding genes that lead to single amino acid substitutions.

                      Alloantibodies to HNAs are known to be responsible in a variety of disorders, including alloimmune neonatal neutropenia, transfusion-related acute lung injury (TRALI),immune neutropenia after bone marrow transplantation, and autoimmune neutropenia. The most commonly implicated HNAs- NA1, NA2, and SH-are located on FcgRIIIb. Gene analysis has shown that NA1 and NA2 differ in five nucleotides, on of which is a silent mutation. In contrast to NA1 and NA2, SH is associated with a single –base mutation in NA2 of the FcgRIIIb gene.

                      Typing of HPAs and HNAs  provides important support of alloantibody detection for the diagnosis and management of immune cytopenic patients. However, this technique is limited by a shortage of well-characterized typing sera, by the need for large numbers of platelets, and by the use of cumbersome serologic assays. Now that the molecular basis underlying HPAs and HNAs has been elucidated, DNA typing techniques can be developed.

                      Several DNA typing techniques have been established, and HPA and HNA genotyping has become more common. However, the procurement of reference DNA for implementation of these methods and for quality control is still a problem for many laboratories.

                      An immortalized B cells derived from individuals carrying defined HPAs and HNAs by Epstein-Barr virus (EBV) transformation. The established DNA panels of B-lymphoblastoid cell lines (B-LCLs) allow genotyping for the genes that encode all the HPAs and HNAs. (Transfusion Vol 40, B.Carl, H.Knoll, G.Bein, and S. SANTOSO)

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