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Anti-CCP3 Ab improve prediction of clinical arthritis in CCP2+ at risk individuals.

OBJECTIVES
i) To determine the prevalence of anti-CCP3 antibodies (Ab) in anti-CCP2 Ab positive (CCP2+) at-risk individuals; ii)) To explore the additional value of anti-CCP3 Ab in CCP2+ at-risk individuals for predicting progression to inflammatory arthritis (IA).


METHODS
Anti-CCP3 Ab were tested on stored serum samples obtained from 347 CCP2+ (BioPlex 2200, BioRad, USA) at-risk individuals without clinical synovitis. Anti-CCP2 and anti-CCP3 titres were categorised as follows: low (LT) and high (HT) for anti-CCP2, negative/low/strong for anti-CCP3. Progression to IA was defined as the development of clinical synovitis in ≥1 joint. Only subjects with ≥1 follow-up visit were included in the progression analysis (n=291).


RESULTS
Anti-CCP3 Ab tended to be either negative (138/347; 39.7%) or strongly positive (189/347; 54.4%), with very few subjects showing a LT (20/347; 5.7%). In contrast, for anti-CCP2 Ab, more LT were observed (103/347; 29.7%). Eighty-eight/291 subjects (30.2%) developed IA. The rate of progression of LT and HT anti-CCP2, when anti-CCP3 was negative, fell from 7.5% to 3.3%, and from 38.9% to 9.8%, respectively. Progression in anti-CCP2 HT increased from 38.9% to 48.4% when anti-CCP3 was strongly positive. The area under the curve was 0.72 for anti-CCP2 (95%CI=0.66-0.78) and 0.76 (95%CI=0.70-0.81) for anti-CCP3 for assessment of progression. In the multivariate analysis, the odds ratio for the development of IA for anti-CCP3 was 1.73 (95%CI 1.20-2.51, p<0.01).


CONCLUSIONS
Anti-CCP3 Ab improve the prediction of IA in CCP2+ at-risk individuals. The impact of anti-CCP3 Ab status for the risk stratification of HT CCP2+ individuals is particularly notable.