Background Antibodies against carbamylated proteins (anti-CarP) are a new type of autoantibodies present in sera of patients with rheumatoid arthritis (RA). These antibodies, measured as the reactivity against carmabylated proteins from Fetal Calf Serum (FCS), do not show cross-reactivity with anti-CCP antibodies, and are associated with radiologic progression both in anti-CCP+ and in anti-CCP– patients .
Objectives The aim of this study was to explore the presence of anti-CarP-FCS antibodies in our collection of patients with RA and their association with clinical and genetic characteristics of the disease.
Methods Carbamylation of FCS proteins was performed as previously described . IgG antibodies against carbamylated FCS were measured by ELISA in sera from 520 RA patients fulfilling 1987 ACR criteria and from 208 healthy donors. Anti-CarP FCS titre was obtained after subtracting reactivity to native FCS from the reactivity to carbamylated FCS. The cut-of for positivity was set as the mean ±2 SD of healthy donors. Association of anti-CarP-FCS with the presence of erosive arthritis, rheumatoid factor (RF), HLADRB1 alleles and the R620W SNP of PTPN22 was analyzed by logistic regression. The relationship between the titre of anti-CarP-FCS and anti-CCP was analyzed with Spearman correlation and the concordance between positivity of anti-CarP-FCS, anti-CCP and RF with the gamma coefficient.
Results Anti-CarP-FCS antibodies were found in 36.1% (188/520) of the patients with RA, including 45.0% of the anti-CCP+ patients and 19.9% of the anti-CCP– patients. Presence and titres of anti-CarP-FCS and anti-CCP antibodies were significantly correlated (g =0.53, P=1.6×10-17 for status concordance, and r=0.27, P=2.1×10-10 for antibody titres, respectively). However, no association was found between anti-CarP-FCS and the risk alleles of HLADRB1 and PTPN22. Anti-CarP-FCS status showed also a significant association with RF status (OR=3.4, P=1.6×10-8) that remained after accounting for anti-CCP status (OR=2.2, P=0.001). In addition, we replicated the association of erosive arthritis with anti-CarP-FCS antibodies (OR=2.3, P=1.4×10-4) even accounting for the presence of anti-CCP (OR=1.6, P=0.026)
Conclusions We have confirmed the presence of anti-CarP-FCS antibodies in RA patients (both anti-CCP+ and anti-CCP– patients) and their association with erosive arthritis as previously described in Dutch patients with RA. These associations indicate the interest of the anti-CarP antibodies in RA. In addition, our finding of lack of association of these antibodies with genetic risk factors for anti-CCP+ RA indicates that this is an independent autoantibody system in RA. We need to further study these antibodies to know if they define a new subgroup of patients with RA.
Shi J et al. Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage. Proc Natl Acad 108:17372-7.
Disclosure of Interest None declared