Compound heterozygosity of HLA-DRB3 * 01:01 and HLA-DRB4 * 01:01 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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: 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 DRB30101 leading to an immune response. STUDY DESIGN AND METHODS: 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. Results: Our Results suggested that, when HPA-1 incompatibility with the husband is found, the presence of two HLA alleles (DRB301:01 and DRB401:01) 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. CONCLUSION: 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.

Original languageEnglish
Pages (from-to)344-352
Number of pages9
JournalTransfusion
Volume53
Issue number2
DOIs
StatePublished - Feb 2013

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