Serum COMP-C3b complexes in rheumatic diseases and relation to anti-TNF-α treatment

Abstract

Introduction: Cartilage oligomeric matrix protein (COMP) is found at elevated concentrations in sera of patients with joint diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA). We recently showed that COMP activates complement via the alternative pathway and that COMP-C3b complexes are present in sera of RA patients, but not in healthy controls. We now set out to elaborate on the information provided by this marker in a variety of diseases and larger patient cohorts.

Methods: COMP-C3b levels in sera were measured by using an enzyme-linked immunosorbent assay (ELISA) capturing COMP and detecting C3b. Serum COMP was measured by using ELISA.

Results: COMP-C3b levels were significantly elevated in patients with RA as well as in systemic lupus erythematosus (SLE), compared with healthy controls. SLE patients with arthritis had significantly higher COMP-C3b levels than did those without. COMP-C3b was furthermore elevated in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, systemic sclerosis, and OA. COMP-C3b did not correlate with COMP in any of the patient groups. COMP-C3b correlated with disease activity in RA, but not in other diseases. COMP-C3b levels in RA patients decreased on treatment with tumor necrosis factor (TNF)-α inhibitors, whereas the levels increased in patients with AS or PsA. The changes of COMP-C3b did not parallel the changes of C-reactive protein (CRP).

Conclusions: COMP-C3b levels are elevated in several rheumatologic diseases and correlate with inflammatory measures in RA. COMP-C3b levels in RA decrease during TNF-α inhibition differently from those of CRP, suggesting that formation of COMP-C3b relates to disease features not reflected by general inflammation measures.

Figure 1

Serum COMP-C3b and COMP in patients with rheumatologic diseases. Serum COMP-C3b (a) and COMP (b) were measured in patients with different rheumatologic diseases. The horizontal bar indicates the median of each group. Statistical significance of differences between disease groups and controls was measured by using a Kruskal-Wallis test with a Dunn multiple comparison posttest. ***P < 0.001; **P < 0.01; *P < 0.05; ns, not significant.

Figure 2

COMP-C3b in SLE patients. Comparison of serum COMP-C3b (a) and COMP (b) in systemic lupus erythematosus (SLE) patients during remission (n = 30) and flare (n = 26). SLE patients with arthritis during flare (n = 11) have higher COMP-C3b than do patients without arthritis during flare (n = 15) (c). Correlation between COMP-C3b and C1q (d), C4 (e), C3 (f) in SLE patients during flare was measured by using the Spearman correlation analysis.

Figure 3

COMP-C3b decreases in rheumatoid arthritis (RA) patients on tumor necrosis factor (TNF)-α inhibition. RA patients (n = 90) receiving infliximab were measured for COMP-C3b (a), C-reactive protein (CRP) (b), and COMP (c) at baseline, after 6 weeks, and after 3 months of treatment. Statistical significance of changes in these parameters was measured with a Friedman test. ***P < 0.001; **P < 0.01; *P < 0.05; ns, not significant.

Figure 4

Serum COMP-C3b increases in patients with ankylosing spondylitis (AS) and PsA on tumor necrosis factor (TNF)-α inhibition. Serum COMP-C3b (a), C-reactive protein (CRP) (b), and COMP (c) were measured in patients with PsA receiving TNF-α inhibition at baseline, after 6 weeks of treatment, and after 3 months of treatment. COMP-C3b (d), CRP (e), and COMP (f) were also measured in AS patients receiving TNF-α inhibition at the same times. Statistical significance of changes in these parameters was measured with a Wilcoxon matched-pairs test because of many missing values at the time point, 3 months. ***P < 0.001; **P < 0.01; *P < 0.05; ns, not significant.