PMID- 36102140 OWN - NLM STAT- MEDLINE DCOM- 20221118 LR - 20230117 IS - 1423-0410 (Electronic) IS - 0042-9007 (Print) IS - 0042-9007 (Linking) VI - 117 IP - 11 DP - 2022 Nov TI - HLA Class II regulation of immune response in sickle cell disease patients: Susceptibility to red blood cell alloimmunization (systematic review and meta-analysis). PG - 1251-1261 LID - 10.1111/vox.13351 [doi] AB - BACKGROUND AND OBJECTIVES: Sickle cell disease (SCD) patients are commonly treated with red blood cell (RBC) transfusion. Pretransfusion tests commonly involve limited serological antibody testing. RBC alloimmunization to RBC antigens is a frequently encountered complication seen in chronically transfused patients. Genetic factors such as the human leukocyte antigen (HLA) are known to influence and regulate immune responses. HLAs are highly polymorphic and play an essential role in regulating immune responses, including RBC alloimmunization. The aim of this study was to conduct a systematic review and meta-analysis to evaluate the association between HLA Class II allelic polymorphisms with the possible risk of developing RBC alloantibodies. MATERIALS AND METHODS: Four databases were systematically searched for relevant studies between the years 2000 and 2021 following the PRISMA guidelines. Four articles met the eligibility and quality criterion, and three alleles, HLA-DRB1*04, HLA-DRB1*15 and HLA-DQB1*03, that were found to be potentially associated with an increased risk in alloantibody formation were included. RESULTS: The primary outcome measure was alloimmunization by RBC antigen exposure in multiply transfused SCD patients. The total estimate of alloimmunization of the SCD patients was 2.33 (95% CI, 1.58-3.44), demonstrating susceptibility to RBC alloantibody formation. Heterogeneity between the studies was insignificant, suggesting the differences associated with random sampling errors. The results showed that SCD patients carry an increased risk of producing RBC alloantibodies. CONCLUSION: A strategy to prevent RBC alloimmunization is genotyping for genetically susceptible SCD patients receiving multiple transfusions. Early identification of genetic variants that can potentially increase the risk of RBC alloimmunization could aid in the screening process and selection of phenotypically matched RBC units. CI - (c) 2022 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion. FAU - Wong, Karmen AU - Wong K AD - Thrombosis and Vascular Diseases Laboratory, School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia. FAU - Lai, Wing Kit AU - Lai WK AD - Thrombosis and Vascular Diseases Laboratory, School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia. FAU - Jackson, Denise E AU - Jackson DE AUID- ORCID: 0000-0001-9044-8009 AD - Thrombosis and Vascular Diseases Laboratory, School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia. LA - eng PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review DEP - 20220914 PL - England TA - Vox Sang JT - Vox sanguinis JID - 0413606 RN - 0 (Isoantibodies) SB - IM MH - Humans MH - Isoantibodies MH - *Anemia, Sickle Cell/genetics/therapy MH - Erythrocytes MH - Erythrocyte Transfusion/adverse effects MH - *Anemia, Hemolytic, Autoimmune/etiology MH - Immunity PMC - PMC9826043 OTO - NOTNLM OT - HLA Class II OT - RBC alloimmunization OT - sickle cell disease COIS- The authors declare that there is no conflict of interest. EDAT- 2022/09/15 06:00 MHDA- 2022/11/19 06:00 PMCR- 2023/01/08 CRDT- 2022/09/14 04:23 PHST- 2022/06/25 00:00 [revised] PHST- 2022/02/16 00:00 [received] PHST- 2022/07/15 00:00 [accepted] PHST- 2022/09/15 06:00 [pubmed] PHST- 2022/11/19 06:00 [medline] PHST- 2022/09/14 04:23 [entrez] PHST- 2023/01/08 00:00 [pmc-release] AID - VOX13351 [pii] AID - 10.1111/vox.13351 [doi] PST - ppublish SO - Vox Sang. 2022 Nov;117(11):1251-1261. doi: 10.1111/vox.13351. Epub 2022 Sep 14.