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. 2015 Feb 7;17(1):25.
doi: 10.1186/s13075-015-0536-2.

Anti-carbamylated protein antibodies in the pre-symptomatic phase of rheumatoid arthritis, their relationship with multiple anti-citrulline peptide antibodies and association with radiological damage

Mikael Brink  1 , Marije K Verheul  2 , Johan Rönnelid  3 , Ewa Berglin  4 , Rikard Holmdahl  5 , Rene E M Toes  6 , Lars Klareskog  7 , Leendert A Trouw  8 , Solbritt Rantapää-Dahlqvist  9
Affiliations

Anti-carbamylated protein antibodies in the pre-symptomatic phase of rheumatoid arthritis, their relationship with multiple anti-citrulline peptide antibodies and association with radiological damage

Mikael Brink et al. Arthritis Res Ther. .

Abstract

Introduction: The presence of a new autoantibody system, anti-carbamylated protein (anti-CarP) antibodies, has been identified in rheumatoid arthritis (RA). The presence of anti-CarP antibodies was evaluated in samples taken from individuals who subsequently developed RA before and after onset of symptoms and related to previously analysed antibodies against citrullinated peptides (ACPA specificities) and anti-CCP2.

Methods: A total of 252 individuals, with 423 samples from before onset of symptoms of RA, and 197 population controls were identified as donors to the Medical Biobank of Northern Sweden; 192 of them were also sampled at the time of diagnosis. All samples were analysed for anti-CarP IgG and anti-CCP2 antibodies using ELISAs. Ten different antibody reactivities against citrullinated antigens (ACPA specificities) were analysed using a custom-made microarray based on the ImmunoCAP ISAC system (Phadia).

Results: The concentration of anti-CarP antibodies was significantly increased in the pre-symptomatic individuals compared with controls (P<0.001) and also increased significantly after disease onset (P<0.001). The sensitivity for anti-CarP antibodies in the pre-symptomatic individuals was 13.9% (95% CI: 11 to 17.6) and 42.2% (95% CI: 35.4 to 49.3) following development of RA. Anti-CarP antibody positivity was found in 5.1% to 13.3% of individuals negative for anti-CCP2 or ACPA specificities. Presence of anti-CarP antibodies was significantly related to radiological destruction at baseline, at 24 months and also to radiological change (P<0.05, all).

Conclusions: The results indicate that anti-CarP antibodies are associated with disease development, even after adjusting for the presence of different ACPA fine specificities, and in anti-CCP2 negative individuals and contribute to the identification of a subset of patients with worse radiological progression of the disease independent of ACPA.

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Figures

Figure 1
Figure 1
Concentrations of anti-CarP antibodies in pre-symptomatic individuals closest to symptom onset (median (IQR) 3.5 (4.9) years) and in controls and patients with RA. Anti-CarP, antibodies against carbamylated protein; IQR, interquartile range; RA, rheumatoid arthritis.
Figure 2
Figure 2
Accumulated percentage of positivity of anti-CarP antibodies, the different ACPA specificities and anti-CCP2 antibodies. ACPA, anti-citrullinated protein antibodies; anti-CarP, antibodies against carbamylated proteins; anti-CCP2, anti-cyclic citrullinated peptide 2.
Figure 3
Figure 3
The relative distribution in percentage of the combinations of positivity and negativity of anti-CarP and anti-CCP2 antibodies illustrated by pie charts. anti-CarP, antibodies against carbamylated proteins; anti-CCP2, anti-cyclic citrullinated peptide 2.
See this image and copyright information in PMC

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