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  • Title: Relevance of the HPA-15 (Gov) polymorphism on CD109 in alloimmune thrombocytopenic syndromes.
    Author: Ertel K, Al-Tawil M, Santoso S, Kroll H.
    Journal: Transfusion; 2005 Mar; 45(3):366-73. PubMed ID: 15752154.
    Abstract:
    BACKGROUND: Alloantibodies against the human platelet (PLT) alloantigen (HPA)-15 system residing on CD109 can cause fetal and neonatal alloimmune thrombocytopenia (FNAIT), posttransfusion purpura, and PLT transfusion refractoriness. The detection of antibodies against HPA-15, however, is hampered by the variable low expression and instability of the CD109 molecule during preparation and storage. STUDY DESIGN AND METHODS: This study analyzed the occurrence of HPA-15 alloantibodies in 1403 patients: 930 FNAIT and 473 polytransfused (PT) patients by modified monoclonal antibody specific immobilization of PLT antigens (MAIPA) assay with well-defined phenotyped PLTs. A DNA typing technique was developed to confirm the phenotypes of PLT donors. B-cell lines were established as sources of reference DNA. RESULTS: Genotyping of 407 unrelated blood donors revealed the gene frequencies 0.512 and 0.488 for HPA-15a and -15b, respectively. Based on the selection of PLTs expressing high amounts of CD109 on the surface (mean fluorescence intensity ratio 4-5 on expression peak on Days 2-4 after apheresis) antibody screening by the MAIPA assay was performed. In total, 16 (1.1%) HPA-15 alloantibodies were found comprising four anti-HPA-15a and 12 anti-HPA-15b. Anti-HPA-15b without other PLT-reactive antibodies were detectable in three serum samples of PT patients. The incidence of HPA-15 alloimmunization in PT patients was significantly higher than in mothers with FNAIT (3.0% vs. 0.22%). In relation to all detected HPA-specific antibodies, HPA-15 is responsible for 6.2 percent of alloimmunizations. CONCLUSION: These observations indicate that alloimmunization against HPA-15 should be considered as a cause for immune thrombocytopenia, particularly in patients receiving multiple PLT transfusions.
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