Contributed equally as first authors.
Article first published online: 7 JUN 2012
© 2012 American Association of Blood Banks
Volume 53, Issue 2, pages 344–352, February 2013
How to Cite
Loewenthal, R., Rosenberg, N., Kalt, R., Dardik, R., Landau, M., Yahalom, V., Avishai, O., Frenkel, O., Gazit, E., Steinberg, D. M., Lipitz, S. and Salomon, O. (2013), Compound heterozygosity of HLA-DRB301:01 and HLA-DRB401:01 as a potential predictor of fetal neonatal alloimmune thrombocytopenia. Transfusion, 53: 344–352. doi: 10.1111/j.1537-2995.2012.03734.x
- Issue published online: 5 FEB 2013
- Article first published online: 7 JUN 2012
- Received for publication March 5, 2012; revision received April 12, 2012, and accepted April 25, 2012.
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 DRB3*0101 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 (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.
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.