Background/Purpose: Anti-cyclic citrullinated peptide antibody (anti-CCP Ab) positivity is closely associated with bone destruction in rheumatoid arthritis (RA) patients, but the correlation between the Ab titer and disease activity is poor. On the other hand, anti-mutated citrullinated vimentin (MCV) Ab, a subset of anti-citrullinated protein/peptide Abs (ACPA), have been suggested to be pathogenic in animal model (Harre U, et al, J Clin Invest, 2012) and an association between negative conversion of this Ab and radiographic remission has been reported in RA patients (Kastbom A, et al. Ann Rheum Dis, 2016). In this study, we aimed to determine the association of negative seroconversion of anti-CCP and MCV Abs with clinical and functional remission of RA.

Methods: Four-hundred and thirty-nine RA patients (female 74.9%, mean age 62.1 years old, and disease duration 8.1 years) who are followed up in our hospital and had anti-CCP and MCV Abs measured sequentially for more than 2 years were enrolled. Both Ab titers were measured using ELISA and the association of negative conversions of these Abs with clinical disease activity was investigated.

Results: 1) There were 12 cases (2.8%) with anti-CCP Ab (cut off 4.5 U/mL) and 57 cases (13.0%) with anti-MCV Abs (cut off 20 IU/mL) those had negative conversion at least once during the course. Whereas negative conversion of anti-CCP Abs was not observed in patients with titers >36.2 U/mL (approximately 8 times of the upper limit of normal) at the first determination, anti-MCV Abs with high titers >35 times of the upper limit of normal decreased to negative. There were cases in which high anti-MCV Ab titer (=719.6 IU/mL) turned to negative in 1 year. In the anti-MCV Ab negative conversion cases, 24.6% of cases with high anti-CCP Ab titers (≧100 U/mL) were also included. 2) In anti-MCV Ab negative conversion cases, disease activity score-ESR (DAS28-ESR) (3.21 vs. 2.44, P< 0.001), simplified disease activity index (7.89 vs.4.29, P< 0.001), and health assessment questionnaire score (0.62 vs.0.49, P< 0.001) were significantly decreased after negative conversion. However, similar changes were not observed in anti-CCP Ab negative conversion cases. 3) Clinical remission using DAS28-ESR was more frequently achieved after negative conversion of anti-MCV Ab than of anti-CCP Ab (67.9 vs. 33.3%, P=0.046). In cases with low disease activity or higher, clinical remission rate was also significantly higher in anti-MCV Ab negative conversion than in anti-CCP Ab negative conversion cases (58.9 vs. 14.3%, P=0.045).

Conclusion: Unlike anti-CCP Ab, negative conversion of anti-MCV Ab was associated with clinical remission. “Immunological remission” with anti-MCV Abs may have clinical implications in RA patients.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-significance-of-negative-seroconversion-of-anti-ccp-and-anti-mutated-citrullinated-vimentin-antibodies-in-patients-with-rheumatoid-arthritis/