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 rheumatic diseases. We evaluated 170 patients with such diseases to determine their serum levels of CH50, C3 and C4 protein. Persistent hypocomplementaemia was found in 19 of those patients, particularly in those with systemic lupus erythematosus (SLE). Cold-dependent activation of complement (CDAC) was demonstrated in nine of the 19 (47.4%), and six of the nine patients demonstrated infection with HCV (66.7%). The nine patients that exhibited CDAC had nearly normal haemolytic complement activity when the sera were separated either at 37 degrees C or in EDTA-treated plasma. Conversely, it markedly decreased, even to the point of being immeasurable, when the sera were separated at 4-21 degrees C. No significant deficiency in C3 and C4 protein levels was found in these patients. Clinical parameters other than levels of anti-HCV antibody, transaminase, and RF were not influenced by CDAC. In an attempt to isolate 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 normal serum and incubated at 4-21 degrees C for 18 h. A decrease in the level of CH50 in normal serum was observed, which predominated (P < 0.001) when precipitates from HCV-infected patients were used. This indicated CDAC was possibly interrelated to the precipitates of such patients. This precipitate was proved to contain IgM besides IgG. It is therefore possible that an HCV-related IgG complex or an IgG-IgM RF complex may be formed at low temperature and be involved in activating the complement system in vitro.