Abstract
This study aimed to review and quantitatively analyze (1) the association of aplastic anemia (AA) with human leukocyte antigen (HLA)-DRB1*15 and HLA-DRB1*15:01 polymorphisms and (2) the association of HLA-DRB1*15 and HLA-DRB1*15:01 polymorphisms with response to immunosuppressive therapy (IST) in AA. Published studies have reported conflicting and heterogeneous results regarding the association of HLA-DRB1*15 and HLA-DRB1*15:01 polymorphisms with response to IST in AA. The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese BioMedical Literature, Wangfang and Chinese Social Sciences Citation Index databases were searched. All relevant publications were searched through December 2015. Odds ratio (OR), risk ratio (RR), and 95% confidence intervals (CI) for the comparison between case–control or cohort studies were evaluated. Finally, 24 articles were identified. For HLA-DRB1*15 and HLA-DRB1*15:01, the OR (95% CI) was 2.24(1.33–3.77), P < 0.01 and 2.50(1.73–3.62), P < 0.01, respectively; and the overall pooled RR was 1.72 (1.30–2.29), P < 0.01 and 1.59 (1.29–1.96), P < 0.01, respectively. Statistical evidence showed no publication bias (P > 0.05). Sensitivity analyses revealed that the results were statistically robust. The meta-analysis suggested that HLA-DRB1*15 and HLA-DRB1*15:01 polymorphisms might be associated with increased AA risk in Asians. IST might be more effective in HLA-DRB1*15+ and HLA-DRB1*15:01+ Asian patients with AA than in HLA-DRB1*15− and HLA-DRB1*15:01− Asian patients with AA. Future studies with adequate methodological quality on gene–gene and gene–environment interactions and gene treatment may yield valid results.
Highlights
Aplastic anemia (AA) is a rare, life-threatening hematopoietic stem cell disorder characterized by peripheral blood cytopenia and bone marrow hypoplasia
A total of 1576 published studies were found examining the relationship between human leukocyte antigen (HLA) polymorphisms and AA
This study systematically reviewed the articles on the relationship of HLA-DRB1Ã15 and HLADRB1Ã15:01 polymorphisms with response to immunosuppressive therapy (IST) in AA
Summary
Aplastic anemia (AA) is a rare, life-threatening hematopoietic stem cell disorder characterized by peripheral blood cytopenia and bone marrow hypoplasia. A large amount of laboratory and clinical data suggest that immune-mediated destruction of hematopoiesis by activated cytotoxic T cells plays an important role in the pathogenesis of AA. The mechanism of activation of cytotoxic T cells is uncertain, but several potential factors related to antigen recognition, susceptibility of immune response, and secretion of cytokines might be involved. Certain human leukocyte antigen (HLA) alleles were suggested to play a role in the activation of autoreactive T-cell clones in patients with AA [2]. Potential roles of HLA-DRB1 polymorphisms have been postulated in many types of autoimmune diseases (e.g., systemic lupus erythematosus and lupus nephritis[3], rheumatoid arthritis[4]). As with most autoimmune diseases, AA is genetically associated with alleles of the HLA [5,6,7,8,9,10,11,12,13,14,15,16,17,18,19]
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