Factors related to seroconversion of anti-cyclic citrullinated peptide antibody after the onset of rheumatoid arthritis: a case-control study and systematic review

Anti-cyclic citrullinated peptide (CCP) antibodies typically present before rheumatoid arthritis (RA) but appear (seroconvert) after disease onset in some patients. This study analyzed factors related to anti-CCP seroconversion. Fifty-six consecutive patients with anti-CCP negative RA were enrolled. The first determination of anti-CCP status was defined as the baseline. Anti-CCP was then reassessed with an interval of 77 (±41) months. Demographics and baseline characteristics were compared between patients with and without anti-CCP seroconversion. Moreover, relevant studies were systematically reviewed. Six of the 56 patients experienced anti-CCP seroconversion (<4.5-12.4 [8.5-65.7] U/mL). These patients were more likely to have interstitial lung disease and HLA-DRB1 shared epitope (SE) alleles and to use biological disease-modifying antirheumatic drugs (bDMARDs). From the systematic review and meta-analysis, bDMARDs, bone erosions, HLA-DRB1 SE and rheumatoid factor positivity were identified as factors related to anti-CCP seroconversion. By selectively screening for anti-citrullinated protein antibody responses, an expansion of the repertoire was observed after the onset of RA. The seroconversion of anti-CCP after the onset of RA is associated with the typical features of RA and may therefore represent an overlooked seropositive disease.