In vivo complement activation influencing complement profiles of rheumatoid arthritis patients without extra-articular symptoms

The split products of C4, C3 and B (C4d, iC3b and Bb, respectively) and newly generated SC5b-9 complex were measured in plasma from patients with rheumatoid arthritis (RA) without extra-articular symptoms. The ratio of each split product to the parent molecule was calculated (C4d/C4, iC3b/C3, Bb/B and SC5b-9/C5) in order to obtain the indices of complement activation independent of the concentration of the parent molecules. C4d, Bb and SC5b-9 levels in patients with RA were higher than those of SLE and the controls. C4d/C4 in RA was lower than that in SLE, while the Bb/B and SC5b-9/C5 ratios of both diseases were not different. The C4d, Bb and SC5b-9 levels and each ratio correlated with each other as well as with the circulating immune complexes containing C3dg (C3dgCIC). C7, C8 and C9 all correlated well with the disease activity of RA, while the split product and SC5b-9 and SC5b-9/C5 did not correlate with the disease activity. We thus conclude that even though there were no extra-articular complications or decreased complement levels in the RA patients, there was a significant degree of complement activation in vivo and these complement levels may be maintained by an increased production which can, as a result, overcome their consumption.