Increased cartilage turnover and circulating autoantibodies in different subsets before the clinical onset of rheumatoid arthritis

Background Previous studies have indicated that autoantibodies may be detected years before the clinical onset of rheumatoid arthritis (RA). Cartilage biomarkers, such as cartilage oligomeric matrix protein (COMP), have not been studied previously in samples collected before the diagnosis of RA. Methods Between 1991 and 1996, 30 447 subjects were included in the Malmo Diet Cancer Study (MDCS). People who developed RA after inclusion were identified by linking the MDCS database to different Swedish registers. One matched control for each validated case was selected from the MDCS. IgG antibodies against cyclic citrullinated peptide (anti-CCP) and mutated citrullinated vimentin (anti-MCV) and IgM rheumatoid factor (IgM RF) were determined by ELISA. Serum COMP was measured with a sandwich ELISA. Results 172 incident cases of RA (median time from inclusion to diagnosis 5 years; range 1-13) were identified. Pre-RA cases were significantly more likely than controls to be positive for anti-CCP (21.9% vs 0.6%), anti-MCV (29.6% vs 3.0%) and IgM RF (18.9% vs 2.4%) (all p < 0.001). Overall, mean serum COMP levels did not differ between cases and controls. Among pre-RA cases included 1-3 years before diagnosis, raised COMP (> 12 U/l) was seen in a greater proportion of anti-CCP-negative than anti-CCP-positive subjects (50% vs 15%; p=0.04). Conclusions Increased cartilage turnover, measured by COMP, and circulating RA-specific antibodies may be distinct processes in the preclinical phase of RA.