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HLA Class II regulation of immune response in sickle cell disease patients: Susceptibility to red blood cell alloimmunization (systematic review and meta-analysis)

Vox Sang. 2022 Nov;117(11):1251-1261 doi: 10.1111/vox.13351.
PICO Summary
POPULATION:

Sickle cell disease (SCD) patients (4 studies).

INTERVENTION:

Systematic review and meta-analysis evaluating the association between human leukocyte antigen (HLA) Class II allelic polymorphisms with the possible risk of developing red blood cell (RBC) alloantibodies.

COMPARISON:

OUTCOME:

Three alleles: HLA-DRB1*04, HLA-DRB1*15 and HLA-DQB1*03, found to be potentially associated with an increased risk in alloantibody formation were included in the systematic review. The primary outcome measure was alloimmunization by RBC antigen exposure in SCD patients receiving multiple transfusions. 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.

Abstract
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.

Metadata
KEYWORDS: HLA Class II; RBC alloimmunization; sickle cell disease
MESH HEADINGS: Humans; Isoantibodies; Anemia, Sickle Cell; Erythrocytes; Erythrocyte Transfusion; Anemia, Hemolytic, Autoimmune; Immunity
Study Details
Study Design: Systematic Review
Language: eng
Credits: Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine