Background/Purpose: Serology represents a powerful tool for the identification and sub-classification of patients with rheumatoid arthritis (RA). IgM-rheumatoid factor and anti-cyclic citrullinated peptide (CCP) antibodies are now part of the 2010 EULAR/ACR criteria for RA. Recently, anti-carbamylated protein (anti-CarP) antibodies have been described to be present over 40% of European patients with RA and to predict joint damage (Shi J et al. PNAS 108:17372, 2011). Here, we have characterized this antibody in Japanese patients with RA.

Methods: Sera of the patients fulfilling ACR diagnostic criteria who visited hospital within 2 yrs after disease onset between April 2003 and March 2006 were obtained. Anti-CarP fetal calf serum (CarP FCS) and anti-CarP fibrinogen (CarP Fib) were measured by using ELISA as before. Anti-CCP2 and anti-CCP3 were detected using commercial assays. Radiographic evaluation was done using van der Heijde-modified Sharp score (SHS), with a range of 0-306 (narrowing + erosion) and expressed as annual change from baseline. Statistical analyses were done using Student’s t-test.

Results: Anti-CarP FCS and anti-CarP Fib antibodies were found in 82/ 258 (31.78%) and 87/ 258 (33.72%) of Japanese patients with RA. Anti-CCP2 and anti-CCP3 antibodies were found in 197/ 258 (76.36%) and 210/ 258 (81.40%) patients, respectively. Among anti-CCP2-positive patients, anti-CarP FCS and anti-CarP Fib were also positive in 78/ 197 (39.59%) and 87/ 197 (44.16%) patients, respectively. Likewise, among anti-CCP3-positive patients, they were positive in 82/ 202 (40.59%) and 87/ 202 (43.07%) of the patients, respectively. Several patients were negative for anti-CCP but positive for anti-CarP: 4/ 258 (1.55%) of the patients were anti-CCP2-negative but anti-CarPFCS-positive; 1/ 258 (0.39%) and 1/ 258 (0.39%) of the patients were anti-CCP3-negative but anti-CarP FCS-positive and anti-CarP Fib-positive, respectively. Radiographic progression as measured by using SHS in the patients positive for anti-CCP3 antibody alone was 10.02±11.48 (n=88), those positive for anti-CCP3 and for either anti-CarP FCS or anti-CarP Fib was 9.45±10.80 (n=61), and those positive for anti-CCP3 and both anti-CarP FCS and anti-CarP Fib antibodies was 36.55±9.25 (n=53); the values statistically significant as compared with 4.57±8.97 of those all negative for anti-CCP3 and anti-CarP antibodies (n=66) at p=0.001, 0.006 and 0.0007, respectively. Radiographic progression depended on the presence, but not the titer, of anti-CCP2, anti-CCP3, anti-CarP FCS and anti-CarP Fib antibodies at baseline.

Conclusion: Anti-CarP antibodies are present in a substantial fraction of Japanese patients with RA to the extent similar to previous findings in Europe.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-carbamylated-protein-antibody-in-japanese-patients-with-rheumatoid-arthritis/