HEPATITIS-C VIRUS (HCV)-INDUCED IGG-IGM RHEUMATOID-FACTOR (RF) COMPLEX MAY BE THE MAIN CAUSAL FACTOR FOR COLD-DEPENDENT ACTIVATION OF COMPLEMENT IN PATIENTS WITH RHEUMATIC DISEASE

A low serum complement level is commonly found in patients with rheuma tic diseases. We evaluated 170 patients with such diseases to determin e their serum levels of CH50, C3 and C4 protein. Persistent hypocomple mentaemia was found in 19 of those patients, particularly in those wit h systemic lupus erythematosus (SLE). Cold-dependent activation of com plement (CDAC) was demonstrated in nine of the 19 (47.4%), and six of the nine patients demonstrated infection with HCV (66.7%). The nine pa tients that exhibited CDAC had nearly normal haemolytic complement act ivity when the sera were separated either at 37 degrees C or in EDTA-t reated plasma. Conversely, it markedly decreased, even to the point of being immeasurable, when the sera were separated at 4-21 degrees C. N o significant deficiency in C3 and C4 protein levels was found in thes e patients. Clinical parameters other than levels of anti-HCV antibody , transaminase, and RF were not influenced by CDAC. In an attempt to i solate the causal factor for CDAC, we isolated IgG fractions from the CDAC patients by using a protein G column, in which case precipitates were collected from the eluates. The precipitates were mixed with norm al serum and incubated at 4-21 degrees C for 18 h. A decrease in the l evel of CH50 in normal serum was observed, which predominated (P < 0.0 01) when precipitates from HCV-infected patients were used. This indic ated CDAC was possibly interrelated to the precipitates of such patien ts. This precipitate was proved to contain IgM besides IgG. It is ther efore possible that an HCV-related IgG complex or an IgG-IgM RF comple x may be formed at low temperature and be involved in activating the c omplement system in vitro.