Particular HLA-DRB1 shared epitope genotypes are strongly associated with rheumatoid vasculitis

Objective. To examine the relationship of the HLA-DRB1 shared epitope (SE) to rheumatoid vasculitis, using individual patient data (IPD) meta-analytic methods. Methods. Published studies that enrolled adult patients with rheumatoid arthritis (RA) were identified by searches of Medline and Embase, and by manual searches of medical journals. All authors were contacted for IPD. Meta-analyses were performed to assess the association of SE presence, dose, and genotype with rheumatoid vasculitis. Results. A total of 14 studies and 1,568 patients (129 with vasculitis) were included in the analysis. RA patients with vasculitis were significantly more likely to have rheumatoid nodules (odds ratio [OR] 2.5, 95% confidence interval [95% CI] 1.5-3.9], but there was no significant association with male sex, rheumatoid factor positivity, or erosive disease. No significant association was observed between the presence of the SE (i.e., 1 or 2 alleles versus 0 alleles) and rheumatoid vasculitis (summary OR 1.4, 95% CI 0.7-2.7). Analysis by SE genotype, however, demonstrated a striking relationship of vasculitis to 3 genotypes containing a double dose of the SE, specifically HLA-DRB1*0401/*0401 (OR 6.2, 95% CI 1.01-37.9), *0401/*0404 (OR 4.1, 95% CI 1.1-16.2), and *0101/*0401 (OR 4.0, 95% CI 1.4-11.6). Conclusion. The HLA-DRB1 SE genotypes *0401/ *0401, *0401/*0404, and *0101/*0401 may be of particular importance to rheumatoid vasculitis. It is hoped that additional investigation of these and other SE genotypes will lead to improved insight into the mechanisms influencing the clinical expression of RA.