Association of anti-citrullinated vimentin and anti-citrullinated α-enolase antibodies with subsets of rheumatoid arthritis

Arthritis Rheum. 2012 Oct;64(10):3102-10. doi: 10.1002/art.34569.

Abstract

Objective: To determine whether the anti-citrullinated vimentin peptide 60-75 (anti-Cit-vimentin) and the immunodominant anti-citrullinated α-enolase peptide 1 (anti-CEP-1) antibodies are associated with subsets of patients with rheumatoid arthritis (RA) independently of the associations between anti-cyclic citrullinated peptide (anti-CCP) antibodies and clinical features of RA.

Methods: The 3 antibody types were quantified by enzyme-linked immunosorbent assay (ELISA) in serum samples from 521 patients with RA and 173 healthy controls of Spanish ancestry. Genotypes for HLA-DRB1 alleles and rs2476601 in PTPN22 were available for these patients and controls plus an additional 106 healthy controls. A combined analysis of the 3 antibodies was conducted using stratified contingency tables and logistic regression models.

Results: A differential, particularly strong, and independent association was observed between the presence of anti-Cit-vimentin antibodies and the presence of shared epitope (SE) alleles, specifically in patients carrying 2 SE alleles, and between the presence of anti- Cit-vimentin antibodies and the prevalence of joint erosion. Associations were observed between anti-CEP-1 positivity and the presence of HLA-DRB1 and PTPN22 risk alleles and their additive interaction. These associations were not accounted for by the anti-CCP status.

Conclusion: Our results indicate that the 2 antibodies against citrullinated peptides analyzed in this study add specific information beyond that obtained with the anti-CCP status. They define subgroups of patients with RA in which genetic factors have different weight and there is an observed difference in the prevalence of erosions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Antibodies / immunology
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology*
  • Disease Progression
  • Epitopes / genetics
  • Epitopes / immunology
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Peptides, Cyclic / immunology*
  • Phosphopyruvate Hydratase / genetics
  • Phosphopyruvate Hydratase / immunology*
  • Vimentin / genetics
  • Vimentin / immunology*

Substances

  • Antibodies
  • Epitopes
  • Peptides, Cyclic
  • Vimentin
  • cyclic citrullinated peptide
  • Phosphopyruvate Hydratase