Background/Purpose: Autoantibodies may be detected years before the onset of rheumatoid arthritis (RA). We have previously shown that levels of Cartilage oligomeric matrix protein (COMP), a marker of cartilage turnover, are elevated in particular in individuals who are negative for anti-CCP antibodies before RA diagnosis. A similar pattern has been reported in early RA (Christensen J Rheumatol 2011; 38:1563-8). Our purpose was to investigate changes in COMP from the pre-clinical phase to early RA, and their relation to anti-CCP status.

Methods: Between 1991 and 1996, 30 447 subjects from a defined catchment area were included in a health survey. From this population, individuals who developed RA after inclusion were identified by linking the health survey database to a community based RA register and local and national patient administrative databases. In a structured review of the medical records, patients were classified according to the 1987 ACR criteria for RA. The identified sample of incident cases of RA was linked to an inception cohort of early RA patients (symptom duration <12 months) from the same area. Serum COMP at baseline and at inclusion as early RA was measured with a sandwich ELISA (AnaMar Medical) among those diagnosed with RA 1-5 years after inclusion in the health survey. Based on previous studies, 12 U/L was used as a cut off for elevated COMP. Anti-CCP2 antibodies were determined by standard methods (Euro-Diagnostica).

Results:

Among a total of 172 incident cases of RA, data on COMP were available from the pre-RA inclusion in the health survey (baseline) and from inclusion in the early RA cohort in 30 cases (22 females/8 males; mean age at RA diagnosis 62 years). The median duration of symptoms was 9 months [interquartile range (IQR) 6-11]. The median time from baseline to inclusion in the early RA cohort was 4.2 years (IQR 3.2-5.2). The proportion of anti-CCP positive individuals increased from 24 % at baseline to 63 % in early RA (p<0.001), and the proportion with elevated COMP levels increased from 20 % to 67 % (p=0.006). The median COMP levels were 10.1 U/L (IQR 8.0-11.9) at baseline and 12.7 U/L (IQR 11.2-14.2) in early RA (p<0.001). The increase in COMP tended to be less pronounced in the subset that was  anti-CCP positive at baseline [median change 1.3 U/L (IQR – 1.0 to 3.8) vs 3.6 U/L (IQR 0.6 to 6.3) in anti-CCP negative pre-RA cases; p=0.16]. COMP levels increased among those who converted from anti-CCP negative to anti-CCP positive (n=12; median change 2.8 U/L) as well as among those who remained anti-CCP negative in early RA (n=10; median change 4.5 U/L). The proportion with elevated COMP levels in early RA was greater among those who were anti-CCP negative at baseline (77 % compared to 43 % in anti-CCP positive pre-RA cases; p=0.16), whereas there was no such difference by anti-CCP status in early RA (anti-CCP negative patients: 73 %; anti-CCP-positive patients: 63%; p=0.70).

Conclusion:

The clinical onset of RA was associated with development of anti-CCP antibodies and increased COMP levels. The increase in COMP was greater among individuals lacking anti-CCP antibodies before the onset of RA. This suggests that RA-specific autoimmunity and increased cartilage turnover may represent distinct pathways in the pre-clinical phase of RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-ccp-antibodies-and-increased-cartilage-turnover-in-patients-developing-rheumatoid-arthritis/