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

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 C3e level in these samples (3.0 +/- 1.3 mg/100 ml) was significantly increased (P less than 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 s 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 Clq binding activity (Clq BA), was observed (P less than 0.001). C3d levels were more elevated in RA patients with extra-articular 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 Clq BA were also significantly correlated (P less than 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, Clq BA, and the clinical activity further appeared during follow-up 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.

Immune complexes and complement catabolism in ankylosing spondylitis.

In serum samples from 37 patients with ankylosing spondylitis (AS), immune complexes were quantitated by the 125I-Clq binding test; in paired plasma samples the C3 breakdown product C3d was measured by an immunochemical method. Compared to results in 30 blood donors, the Clq binding activity was significantly (greater than 2 SD), although discretely, increased in 5 of 8 patients with seropositive AS, but not in other AS patients. All C3d levels were within the normal range. In a parallel investigation, increased Clq binding activity and C3d levels were found in 87% and 90%, respectively, of patients with seropositive rheumatoid arthritis.

Behaviour of synovial complement C3 and C4 components in inflammatory and degenerative joint diseases, before and after synoviorthesis.

The synovial fluid beta1a (C3) and beta1e (C4) expressed by their ratio to corresponding serum concentrations) were studied in 31 cases of seropositive rheumatoid arthritis (RA+), 5 cases of seronegative rheumatoid arthritis (RA-1), and 15 cases of osteoarthrosis (OA) before osmic acid synoviorthesis on knees. This was repeated after synoviorthesis in the synovial fluid (SF) of 24 RA+, 4 RA-, and 10 OA patients. The following studies were undertaken: (a) the relationship between these components; (b) their correlation with the SF protein concentration and rheumatoid factor titre, when present. This analysis led us to the following conclusions. (1) Before synoviorthesis (a) The SF beta1e is significantly lower than beta1a in RA+. In OA, an inverse phenomenon is observed. (b) The concentration of beta1a and beta1e are proportional to the protein concentration in the SF of OA. A significant inverse relationship between beta1a, beta1e, and the titre of rheumatoid factor is found. (2) after synoviorthesis the same studies performed on knees at the time of one or more relapses shows that the same pathogenetic process is involved and that the immunological mechanism is little influenced by this treatment. In OA also the relapse differs very little from the initial process observed before synoviorthesis.