Lack of association of the HLA-DRB1 shared epitope with rheumatoid nodules: an individual patient data meta-analysis of 3,272 Caucasian patients with rheumatoid arthritis

Arthritis Rheum. 2004 Mar;50(3):753-62. doi: 10.1002/art.20119.


Objective: The objective of this individual patient data (IPD) meta-analysis was to examine the relationship of rheumatoid nodules to the HLA-DRB1 shared epitope (SE) and to individual SE genotypes.

Methods: English-language studies that enrolled adult non-Hispanic Caucasian 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-analysis was performed to assess the association of SE presence, dose, and genotype with rheumatoid nodules. Meta-analyses adjusted for disease duration and cumulative meta-analyses were also performed to assess the influence of RA duration and year of study publication on the results.

Results: A total of 24 studies and 3,272 patients were available for analysis. IPD were obtained for 22 of the studies. There was a nonsignificant association between the presence of the SE (i.e., 1 or 2 alleles versus 0 alleles) and rheumatoid nodules (summary odds ratio [OR] 1.3, 95% confidence interval [95% CI] 0.97-1.6). Analysis by SE genotype, however, demonstrated a weak relationship with inheritance of a single DRB1*0401 SE allele (OR 1.4, 95% CI 1.1-1.8). No other genotypes achieved statistical significance in the adjusted or unadjusted analyses.

Conclusion: The presence of the HLA-DRB1 SE does not appear to significantly increase the risk of rheumatoid nodules among Caucasian patients with RA. Analysis by DRB1 SE genotype was uninformative, suggesting only a potential (and at most modest) role of the DRB1*0401 SE allele. Results from this IPD meta-analysis implicate other genetic, stochastic, and/or environmental factors in the susceptibility to rheumatoid nodules.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Epitopes*
  • Female
  • Genotype
  • HLA-DR Antigens / genetics
  • HLA-DR Antigens / immunology*
  • HLA-DRB1 Chains
  • Humans
  • Male
  • Middle Aged
  • Rheumatoid Nodule / genetics
  • Rheumatoid Nodule / immunology*


  • Epitopes
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • HLA-DRB1*04:01 antigen