Measurement of terminal complement complexes in rheumatoid arthritis

Though complement activation is recognized as a central event in inflammation in the rheumatoid joint, little attention has been paid to the role of the cytolytic membrane attack complex of complement in the pathogenesis of this disease. The membrane attack complex causes a variety of non-lethal effects in nucleated cells, including stimulation of release of inflammatory mediators, and cell proliferation. Thus in the rheumatoid synovium, non-lethal effects of complement membrane attack may play a major role in disease pathology. In order to investigate this possibility, assays for the detection of terminal complement complexes in biological fluids have been established, and used to demonstrate membrane attack pathway activation in rheumatoid arthritis. Terminal complement complexes were present in increased levels in synovial fluid (mean, 1,334 ng/ml) and plasma (mean, 513 ng/ml) in 20 patients with rheumatoid arthritis when compared with controls (mean, 285 ng/ml and 129 ng/ml respectively). Using an assay specific for the SC5b-9 complex it was demonstrated that the raised levels of terminal complement complexes in rheumatoid synovial fluid consisted of a mixture of inactive SC5b-9 complexes and fluid-phase complement membrane attack complexes.