Complement activation, circulating C1q binding substances and inflammatory activity in rheumatoid arthritis:...

Patients with rheumatoid arthritis were treated with podophyllotoxin derivatives (PTD) or with cyclophosphamide. Increased concentrations of C1r-C1s-C1 inactivator complexes (C1r-C1s-C1 IA) in serum provided evidence for C1 activation, which was most pronounced before treatment. During treatment the levels of C1r-C1s-C1 IA clearly decreased, while the levels of C4 increased. This rise in C4 was contrasted to the decrease in other acute phase reactants as C-reactive protein. Circulating immune complexes were assessed by the C1q deviation test (C1q DV) and the C1 binding assay (C1q BA). Discrepancies were noted in the outcome of the two assays. Of parameters reflecting C1 inactivation C1r-C1s-C1 IA complexes were positively and C4 negatively correlated with the inflammatory activity as measured by synovitis index (SI). The values in C1q DV correlated with the C1r-C1s-C1 IA values and with SI. In contrast, C1q BA correlated with CRP but not with C1r-C1s-C1 IA or SI. The study gave evidence for a relationship between C1 activation as detected in serum and the extent of synovial inflammation in RA. The possibility is discussed that substances other than immune complexes may be involved in C1 activation and contribute to the synovial inflammation.