Background/Purpose:

Several studies have identified anti-cyclic citrullinated peptide (CCP) antibodies as an important indicator for destructive disease in patients with juvenile idiopathic arthritis (JIA). This is of particular significance in patients with IgM rheumatoid factor (RF)-positive polyarticular JIA, which closely resembles rheumatoid arthritis (RA). While the role of anti-CCP antibodies in RA and JIA is better understood, the identity of the target proteins of this modification remains undefined. We evaluated serum from patients with JIA to investigate the presence of anti-citrullinated type II collagen (CII) and anti-citrullinated vimentin antibodies, and their association with RF and anti-CCP antibody isotypes and previously measured anti-citrullinated fibrinogen and α-enolase antibodies. Our aim was to determine the prevalence and significance of previously identified target proteins for citrullination and elucidate their role in the disease process of JIA.

Methods:

Sera were obtained from 96 patients with various JIA subtypes, 19 systemic lupus erythematous (SLE) patients, and 10 healthy children. All sera were measured for antibodies against citrullinated and native CII and vimentin (vim1-16, vim59-74) by ELISA. Results were compared to anti-CCP antibody and RF isotypes, and our previously measured anti-citrullinated fibrinogen antibodies and anti-citrullinated α-enolase antibodies, in addition to erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).

Results: 

Mean levels of all anti-citrullinated antibodies were significantly higher in JIA patients than in healthy children (p<0.05). The most commonly detected citrullinated autoantibodies were anti-citrullinated CII (33.3%) and anti-citrullinated fibrinogen antibodies (32.3%), with the least commonly detected being anti-citrullinated α-enolase antibodies (9.4%). One IgM RF-positive polyarthritis patient was positive for all tested anti-citrullinated autoantibodies. The most common combination of positivity was anti-citrullinated CII and anti-citrullinated fibrinogen antibodies in 7 patients. Twenty-two subsets of patients were identified based on their anti-citrullinated autoantibody profile, not including anti-CCP antibody isotypes. Anti-citrullinated CII antibodies correlated significantly with all other citrullinated autoantibodies (p<0.05). Anti-citrullinated vimentin 1-16 and 59-74 demonstrated strong correlation with each other, and both correlated significantly with anti-citrullinated fibrinogen and alpha-enolase antibodies (p<0.05). Anti-citrullinated vimentin 1-16 antibodies also correlated with ESR (p<0.05). When including the group of citrullinated autoantibodies in logistic regression analysis, anti-citrullinated fibrinogen remained as the only autoantibody significantly correlated with joint damage (p<0.05).

Conclusion:

This study demonstrates that multiple citrullinated epitopes can be detected in JIA patients, especially those patients with polyarticular disease. Anti-citrullinated fibrinogen antibodies remained as the single citrullinated autoantibody to correlate significantly with joint damage.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/evaluation-of-anti-citrullinated-type-ii-collagen-and-anti-citrullinated-vimentin-antibodies-in-patients-with-juvenile-idiopathic-arthritis/