Association of HLA-DR, HLA-DQ, and HLA-B alleles with inclusion body myositis risk: A systematic review, a meta-analysis, a meta-regression and a trial sequential analysis.

Introduction: Although, several studies have assessed the association of HLA Class I and II genes with inclusion body myositis (IBM), results were inconsistent and between-studies heterogeneity needs to be investigated.

Objectives: The aim of this review was to summarize existing data on the contribution of HLA-DRB1 and HLA-B alleles to IBM susceptibility and to investigate the between-studies heterogeneity by subgroup analyses and meta-regressions.

Design: This study was performed according to the PRISMA guidelines for systematic reviews and meta-analyses.

Methods: An electronic literature search for eligible studies among all papers published prior to January 29, 2025, was conducted through PubMed, EMBASE, Web of science, and Scopus databases. Meta-analyses together with subgroup analyses and meta-regressions were performed for the two following HLA genes: HLA-DRB1 and HLA-B.

Results: Combined analyses revealed a significant increase in IBM risk conferred by the HLA-DRB1*03 allele (9.21 (7.05-12.01)), the DRB*03:01 allele (8.44 (6.85-10.41)), the DRB1*01 allele (2.31 (1.82-2.93)), the DRB1*01:01 allele (2.63 (1.95-3.55)), the DRB1*15:02 allele (3.49 (2.12-5.75)), the B*08 allele (4.05 (2.58-6.38)), and the DQB1*02 allele (6.62 (4.5-9.74)), all p-values < 0.001. In addition, the DRB1*15:01 allele was found to be protective against IBM in all populations (0.48 (0.32-0.72)). Conversely, the DRB*11 allele was not associated with IBM risk, OR (95% CI) = 0.91 (0.54-1.51), p = 0.703.

Conclusion: This meta-analysis demonstrated that HLA-DRB1, DQB1, and B loci could play a major role in IBM pathogenesis.

Registration: This review has been registered on PROSPERO on June 25, 2024: CRD42024557948, Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024557948.