Protective effect of HLA-DQB1 alleles against alloimmunization in patients with sickle cell disease |
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| Affiliation: | 1. Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National Health System, 111 Michigan Avenue, N.W., Washington, DC, United States;2. Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, United States;3. Integrative Systems Biology, George Washington University School of Medicine and Health Sciences, Washington, DC, United States;4. Center for Genetic Medicine Research, Children’s National Health System, Washington, DC, United States;5. Division of Hematology and Oncology, Children’s National Health System, Washington, DC, United States;6. Division of Laboratory Medicine, Children’s National Medical Center, Washington, DC, United States;7. Department of Biostatistics, Cato Research, Durham, NC, United States;8. Laboratoire Jean Dausset and LabEx Transplantex, INSERM UMRS 1160, Monacord and ESH, Hôpital Saint-Louis, Paris, France;9. Division of Pediatric Hematology/Oncology, University of Michigan Health System, Ann Arbor, MI, United States;10. Section of Hematology/Oncology, University of Illinois Comprehensive Sickle Cell Center, Chicago, IL, United States |
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| Abstract: | BackgroundAlloimmunization or the development of alloantibodies to Red Blood Cell (RBC) antigens is considered one of the major complications after RBC transfusions in patients with sickle cell disease (SCD) and can lead to both acute and delayed hemolytic reactions. It has been suggested that polymorphisms in HLA genes, may play a role in alloimmunization. We conducted a retrospective study analyzing the influence of HLA-DRB1 and DQB1 genetic diversity on RBC-alloimmunization.Study designTwo-hundred four multi-transfused SCD patients with and without RBC-alloimmunization were typed at low/medium resolution by PCR-SSO, using IMGT–HLA Database. HLA-DRB1 and DQB1 allele frequencies were analyzed using logistic regression models, and global p-value was calculated using multiple logistic regression.ResultsWhile only trends towards associations between HLA-DR diversity and alloimmunization were observed, analysis of HLA-DQ showed that HLA-DQ2 (p = 0.02), -DQ3 (p = 0.02) and -DQ5 (p = 0.01) alleles were significantly higher in non-alloimmunized patients, likely behaving as protective alleles. In addition, multiple logistic regression analysis showed both HLA-DQ2/6 (p = 0.01) and HLA-DQ5/5 (p = 0.03) combinations constitute additional predictor of protective status.ConclusionOur data suggest that particular HLA-DQ alleles influence the clinical course of RBC transfusion in patients with SCD, which could pave the way towards predictive strategies. |
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| Keywords: | HLA-DQB1 HLA-DRB1 Alloimmunization Red Blood Cell transfusion Sickle cell disease |
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