Mixed cryoglobulinemia: new concepts

The most documented extrahepatic manifestation of hepatitis C virus (HCV) i nfection is mixed cryoglobulinemia (MC). MC is characterised by the presenc e of temperature-sensitive protein complexes: in type II MC, cryoglobulins are composed of a monoclonal rheumatoid factor (usually, IgM kappa) against polyclonal IgG. In type III MC, all components are polyclonal. The presenc e of microheterogeneity and other new types of cryoglobulins is a novel and recent observation. The production of different autoantibodies and circula ting immune complexes, including the cryoglobulins, are responsible for sys temic vasculitis and various organ damage. In a limited number of MC patien ts, a malignancy, that is B-cell non-Hodgkin's lymphoma or hepatocellular c arcinoma, may also develop. Finally, results of interferon and/or ribavirin treatments in MC patients represent an indirect proof for the pathogenetic link between MC and HVC infection. The discovery of the relation between H CV infection and MC shows the striking association between a viral infectio n and an autoimmune disease and, thus, a potential link between the systemi c autoimmune and lymphoproliferative disorders.