The extent of the anti-citrullinated protein antibody repertoire is associated with arthritis development in patients with seropositive arthralgia

Ann Rheum Dis. 2011 Jan;70(1):128-33. doi: 10.1136/ard.2010.132662. Epub 2010 Nov 9.

Abstract

Objectives: To determine the fine specificity of anti-citrullinated protein antibodies (ACPA) in the early phase of arthritis development, the ACPA repertoire in arthralgia patients and the association with arthritis development were studied.

Methods: A total of 244 patients with arthralgia positive for anti-cyclic citrullinated peptide antibodies (aCCPs) and/or IgM rheumatoid factor (IgM-RF), without arthritis were included. Development of arthritis was defined as presence of one or more swollen joints at clinical examination during follow-up. Sera were tested at baseline for reactivity to five citrullinated peptides derived from fibrinogen (three), vimentin (one) and α-enolase (one) and five corresponding arginine peptides in an ELISA.

Results: In all, 69 patients (28%) developed arthritis in a median of 3 joints after a median follow-up of 11 (IQR 5-20) months. Reactivity to each peptide was significantly associated with arthritis development (p<0.001). The ACPA repertoire did not differ between patients who did or did not develop arthritis. Among aCCP-positive patients, patients recognising two or more additional citrullinated peptides developed arthritis more often (p=0.04). The number of recognised peptides was positively associated with the aCCP level (p<0.001). Crossreactivity between different peptides was minimal.

Conclusions: Arthritis development is not associated with recognition of a specific citrullinated peptide once joint complaints are present. The ACPA repertoire in some patients with arthralgia is expanded. High aCCP levels are associated with a qualitatively broad ACPA repertoire. Patients with an extended ACPA repertoire have a higher risk of developing arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arthralgia / genetics
  • Arthralgia / immunology*
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology*
  • Autoantibodies / blood*
  • Biomarkers / blood
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Histocompatibility Testing
  • Humans
  • Immunoglobulin M / blood
  • Male
  • Middle Aged
  • Peptides, Cyclic / immunology*
  • Prognosis
  • Rheumatoid Factor / blood

Substances

  • Autoantibodies
  • Biomarkers
  • Immunoglobulin M
  • Peptides, Cyclic
  • cyclic citrullinated peptide
  • Rheumatoid Factor