Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis

Arthritis Rheum. 2007 Aug;56(8):2503-11. doi: 10.1002/art.22817.


Objective: Modification of antigens represents a trigger for the generation of autoantibodies. In the pathogenesis of rheumatoid arthritis (RA), citrullination of proteins has been shown to be a critical process, and the determination of antibodies against citrullinated antigens has been a diagnostic milestone. We undertook this study to determine whether antibodies to mutated and citrullinated vimentin (MCV) could serve as a diagnostic and prognostic marker for RA.

Methods: We identified novel isoforms of human MCV in the synovial fluid of RA patients. The significance of these disease-related modifications was investigated by the analysis of autoantibody reactivities. In a group of 1,151 RA patients, the diagnostic significance and the prognostic value of an anti-MCV enzyme-linked immunosorbent assay (ELISA) were compared with that of an anti-cyclic citrullinated peptide (anti-CCP) ELISA.

Results: In RA, sensitivities of 82% and 72% were calculated for the anti-MCV and anti-CCP assays, respectively. The specificity of both assays was comparable (98% and 96%, respectively). In followup analyses of 16 RA patients with moderate disease activity (mean Disease Activity Score in 28 joints [DAS28] of 2.72) and 26 RA patients with active disease (mean DAS28 of 5.07), disease stratification of RA was possible using the anti-MCV assay (P = 0.0084). A significant correlation of anti-MCV antibodies with the DAS28 was documented (r = 0.5334, P = 0.0003), in 42 RA patients (n = 427 antibody determinations at different time points).

Conclusion: Antigenic properties of vimentin were determined by mutation and citrullination. Anti-MCV antibodies are a novel diagnostic marker for RA. Furthermore, they may allow monitoring and-if confirmed in even larger series of patients-stratification of disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism*
  • Arthritis, Rheumatoid / physiopathology
  • Autoantibodies / blood
  • Autoantigens / genetics
  • Autoantigens / immunology
  • Autoantigens / metabolism*
  • Biomarkers / metabolism
  • Cell Line
  • Citrulline / immunology
  • Citrulline / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Male
  • Middle Aged
  • Mutation
  • Oxidative Stress / drug effects
  • Protein Isoforms
  • Recombinant Proteins
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Synovial Fluid / chemistry
  • Tandem Mass Spectrometry
  • Vimentin / genetics
  • Vimentin / immunology
  • Vimentin / metabolism*


  • Autoantibodies
  • Autoantigens
  • Biomarkers
  • Protein Isoforms
  • Recombinant Proteins
  • Vimentin
  • Citrulline
  • Hydrogen Peroxide