THE ETIOLOGY OF MIXED CRYOGLOBULINEMIA ASSOCIATED WITH HEPATITIS-C VIRUS-INFECTION

A strong association of hepatitis C infection (HCV) with 'essential' m ixed cryoglobulinaemia has been established. The demonstration of HCV in Type II mixed cryoglobulins with monoclonal rheumatoid factors (mRF ) that bear the WA crossidiotype has lead to the hypothesis that mixed cryoglobulins result from chronic stimulation by HCV-lipoprotein of a population of XId WA+B-1a cells. The reactivity of WA IgM intially pr oduced is with the HCV-self antigen complex with RF activity resulting secondarily from the pausi-mutational process accompanying the T cell independent process. This benign proliferation progreses by multi ste p mutations to malignancy in a minority of patients. The implications of the hypothesis for understanding the physiology of certain natural auto antibodies and for therapeutic invervention in this disease are d iscussed.