Anti-carbamylated protein antibodies are present in arthralgia patients and predict the development of rheumatoid arthritis

Arthritis Rheum. 2013 Apr;65(4):911-5. doi: 10.1002/art.37830.


Objective: Recently, we discovered a new autoantibody system in rheumatoid arthritis (RA): anti-carbamylated protein (anti-CarP) antibodies. These antibodies have value in predicting joint destruction; however, it is not clear whether they are present before the diagnosis of RA and whether they have value as predictors of RA development. Therefore, we studied whether anti-CarP antibodies are present in patients with arthralgia and whether their presence is associated with the development of RA.

Methods: Sera from 340 arthralgia patients who did not have clinical signs of arthritis but who were positive for IgM rheumatoid factor (IgM-RF) and/or anti-cyclic citrullinated peptide 2 (anti-CCP-2) and 32 healthy controls were tested for anti-CarP IgG antibodies. Of the patients with arthralgia, 111 were IgM-RF positive/anti-CCP-2 antibody negative and 229 were anti-CCP-2 antibody positive. Patients were observed for the development of RA (based on the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria) during a median followup period of 36 months. Cox proportional hazards regression analysis was performed to compare the risk of developing RA between arthralgia patients who were positive for anti-CarP antibodies and those who were negative for anti-CarP antibodies during followup.

Results: Anti-CarP antibodies were present in the sera of 39% of the patients. One hundred twenty patients developed RA, after a median of 12 months (interquartile range [IQR] 6-24). The presence of anti-CarP antibodies was associated with the development of RA in the entire arthralgia cohort after correction for RF and anti-CCP-2 antibody status (hazard ratio 1.56 [95% confidence interval 1.06-2.29], P=0.023), as well as in the anti-CCP-2 antibody-positive subgroup (odds ratio 2.231 [95% confidence interval 1.31-3.79], P=0.003).

Conclusion: Anti-CarP antibodies are present in patients with arthralgia, and their presence predicts the development of RA independent of anti-CCP-2 antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arthralgia / blood
  • Arthralgia / immunology*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / immunology*
  • Autoantibodies / blood*
  • Carbamates / immunology*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Immunoglobulin M / blood
  • Immunoglobulin M / immunology
  • Male
  • Middle Aged
  • Peptides, Cyclic / blood
  • Peptides, Cyclic / immunology
  • Prodromal Symptoms
  • Proportional Hazards Models
  • Proteins / immunology*
  • Rheumatoid Factor / blood
  • Rheumatoid Factor / immunology


  • Autoantibodies
  • Carbamates
  • Immunoglobulin G
  • Immunoglobulin M
  • Peptides, Cyclic
  • Proteins
  • cyclic citrullinated peptide
  • Rheumatoid Factor