Circulating complement breakdown products in patients with rheumatoid arthritis. Correlation between plasma C3d, circulating immune complexes and clinical activity

Abstract

Quantitative determination of the small C3 breakdown product, C3d, was used to investigate complement activation in 45 plasma samples from 30 patients with rheumatoid arthritis (RA). The mean plasma C3d level in these samples (3.0 ± 1.3 mg/100 ml) was significantly increased (P < 0.001) as compared to patients with degenerative joint disease (0.9 ± 0.4 mg/100 ml) and healthy blood donors (0.8 ± 0.5 mg/100 ml). C3d levels were increased by more than 2 SD in 79% of RA samples. Plasma C3d levels were compared with C3d concentrations in synovial fluid. In most RA patients, the C3d levels were higher in synovial fluid than in plasma. A very significant correlation between plasma C3d levels and circulating immune complexes, as measured by determination of C1q binding activity (C1q BA), was observed (P < 0.001). C3d levels were more elevated in RA patients with extraarticular disease manifestations (3.8 ± 1.2 mg/100 ml) as compared to patients with joint disease alone (2.2 ± 1.0 mg/100 ml). C3d levels and C1q BA were also significantly correlated (P < 0.001 with the RA disease activity expressed by an index derived from sedimentation rate, joint score, and duration of morning stiffness. A close relationship between C3d levels, C1q BA, and the clinical activity further appeared during followup studies. The present observations suggest that a parallel but rather independent activation of the complement system may be induced by immune complexes in circulating blood and in the joint spaces during the course of rheumatoid arthritis.