Compound heterozygosity of HLA-DRB301:01 and HLA-DRB401:01 as a potential predictor of fetal neonatal alloimmune thrombocytopenia.

Ron Loewenthal, Nurit Rosenberg, Rivka Kalt, Rima Dardik, Meytal Landau, Vered Yahalom, Ofelia Avishai, Orit Frenkel, Ephraim Gazit, David M Steinberg, Shlomo Lipitz, Ophira Salomon

Tissue Typing Laboratory, the Fetal Medicine Unit, Department of Obstetrics and Gynecology, Sheba Medical Center, Tel Hashomer, Israel.

Transfusion 2013 Feb

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Fetal neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening bleeding disorder in the fetus or neonate caused by maternal alloantibodies directed against fetal platelet (PLT) antigens inherited from the father. The immune-dominant antigen leading to severe FNAIT is the human PLT antigen (HPA)-1, whose polymorphism constitutes an epitope for human leukocyte antigens (HLAs), usually DRB3*0101 leading to an immune response. In this study our aims were to find whether other allele variants of the β subunit of the HLA-DR family specifically focused on the HLA residues that bind Position 33 of the HPA-1 integrin contribute to FNAIT development and affect response to treatment and whether coexistence of both anti-HPA-1a and anti-HLA class I specific against the father's antigens leads to a more severe thrombocytopenia in the newborn. We examine the genotype of 23 mothers to newborns with FNAIT compared to a control group. Our results suggested that, when HPA-1 incompatibility with the husband is found, the presence of two HLA alleles (DRB3*01:01 and DRB4*01:01) in the mother increases the risk and severity of FNAIT and reduces the success of a preventive immunoglobulin G treatment. We provide a structural model for the molecular basis of the rational effects of the different HLA alleles. In addition, we found that the presence of both anti-HPA-1 and anti-HLAs did not aggravate FNAIT in comparison to mothers harboring only anti-HPA-1. Overall, we suggest that a specific genotyping of the mother in relation to HLA-DRB as well as HPA-1 can serve as an antenatal diagnostic tool, particularly in siblings of women who gave birth to neonates with FNAIT. © 2012 American Association of Blood Banks.

Citation

Ron Loewenthal, Nurit Rosenberg, Rivka Kalt, Rima Dardik, Meytal Landau, Vered Yahalom, Ofelia Avishai, Orit Frenkel, Ephraim Gazit, David M Steinberg, Shlomo Lipitz, Ophira Salomon. Compound heterozygosity of HLA-DRB3*01:01 and HLA-DRB4*01:01 as a potential predictor of fetal neonatal alloimmune thrombocytopenia. Transfusion. 2013 Feb;53(2):344-52