The aetiology of mixed cryoglobulinaemia associated with hepatitis C virus infection.

A strong association of hepatitis C infection (HCV) with 'essential' mixed 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 initially produced 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 progresses by multi step 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 intervention in this disease are discussed.