Levels of C4d, a fragment of C4 generated during activation of the classical complement pathway, were measured in the plasma of 77 patients with rheumatoid arthritis and 30 healthy subjects. Disease activity was judged according to Ritchie's articular index to be mildly active in 31 (group 1), moderately active in 29 (group 2), and severely active in 17 patients (group 3). Plasma levels of C3d, a fragment of C3, and serum levels of C4, C3, and immune complexes were also measured. The ratios C4d/C4 and C3d/C3 were calculated. The C4d/C4 and C3d/C3 ratios and the levels of circulating immune complexes correlated with the degree of disease activity without significantly departing from linear trend and discriminated between patients with different grades of disease activity. C4d, C3d, C4, and C3 also correlated with disease activity but in a non-linear relationship. A significant correlation was found between C4d and C3d, and between C4d/C4 and C3d/C3. C4d and C4d/C4 also correlated with circulating immune complexes. These results indicate that indices of C4 and C3 activation, in particular the ratios C3d/C3 and C4d/C4, provide a sensitive assessment of disease activity in rheumatoid arthritis, and confirm the major part played by the classical complement pathway in the pathogenesis of this disease.
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