Multiple Types of Immune Complexes in Patients with Mixed Cryoglobulinemia

The sera of 13 patients with mixed cryoglobulinemia were examined for the presence of circulating immune complexes with the 125I-C1q binding assay before and after precipitation of cryoglobulins. All 13 patients had increased C1q binding activity(>10%) prior to cryoprecipitation (mean C1q binding activity =69%) and 10 of 13 had increased C1q binding activity after precipitation and removal of cryoglobulin (mean C1q binding activity = 41%). Decrements in serum C1q binding activity caused by cryoprecipitation ranged from minimal to marked (1–73%). Since all of these sera contained IgM rheumatoid factor, 7 were treated with 2-mercaptoethanol, known to dissociate 19S IgM into its subunits, and then tested for C1q binding activity and rheumatoid factor. 2-mercaptoethanol eliminated rheumatoid factor activity in all cases, but C1q binding activity remained elevated in 6 to 7 sera, thus indicating the presence of immune complexes distinct form 19S IgM rheumatoid factor complexes. By contrast absorption of 9 mixed cryoglobulinemia sera with solid-phase protein A resulted in the disappearance of immune complex-like material from the test sera, suggesting that IgG is a major constituent of the C1q binding material. Addition of eluate from the solid phase protein A to normal sera resulted in the appearance of increased C1q binding activity. Hepatitis B surface antigen was detected in the protein A eluate of two of six patient tested, and antibody to hepatitis B surface antigen was detected in the protein A eluate of a third patient. These findings indicate that in addition to cryoglobulins patients with mixed cryoglobulinemia have circulating immune complexes that are noncryoprecipitable. The immune complexes contain predominantly IgG and are, in most cases, distinct form 19S IgM rheumatoid factor complexes. In some cases the immune complexes may contain hepatitis B surface antigen or antibody.