The Aetiology of Mixed Cryoglobulinaemia Associated with Hepatitis C Virus Infection

Abstract

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.

Hepatitis C virus, non-Hodgkin's lymphomas and hepatocellular carcinoma

“…Previously, a strong association of HCV infection with immunocytoma has been suggested (Silvestri et al, 1997), although the prevalence was not as high as in the NHL cases localized at the liver and major salivary glands reported herein. Thus, as already hypothesized (Agnello, 1995;De Vita et al, 1995), the role of HCV in the development of NHL involving liver or salivary glands may be similar to that of Helicobacter pylori in gastric MALT lymphomas. Conversely, gastric NHL resembled other NHLs with respect to HCV prevalence.…”

“…HCV infection has been associated with certain extrahepatic manifestations, particularly mixed cryoglobulinaemia (MC), membranoproliferative glomerulonephritis, porphyria cutanea tarda and, possibly, autoimmune thyroiditis and Sjogren's syndrome (Gumber and Chopra, 1995). The demonstration of HCV in type II mixed cryoglobulins with monoclonal rheumatoid factor has led to the hypothesis that mixed cryoglobulins result from chronic stimulation by HCV of a population of B cells (Agnello, 1995;Sansonno et al, 1996). Benign proliferation of B cells progresses to frank malignancy in a proportion of patients (Agnello, 1995;Monteverde et al, 1995).…”

“…The demonstration of HCV in type II mixed cryoglobulins with monoclonal rheumatoid factor has led to the hypothesis that mixed cryoglobulins result from chronic stimulation by HCV of a population of B cells (Agnello, 1995;Sansonno et al, 1996). Benign proliferation of B cells progresses to frank malignancy in a proportion of patients (Agnello, 1995;Monteverde et al, 1995).…”

Low density lipoprotein receptor as a candidate receptor for hepatitis C virus

“…Heterogeneities with respect to buoyant density and sedimentation of HCV RNA-carrying material (HCVrcm) have been reported in different groups of patients, and have been partly attributed to the binding of viral particles to ␤-lipoproteins (low density lipoprotein [LDL], very low density lipoprotein [VLDL]) and immunoglobulins (IgG/IgM) [Thomssen et al, 1992[Thomssen et al, , 1993Hijikata et al, 1993;Prince, 1994;Agnello, 1995;Prince et al, 1996]. We discussed previously the role of lipoproteins in persistence and virus-cell interactions of HCV [Thomssen et al,1993;Monazahian et al, 1995].…”

Hepatitis C Related Vasculitides

“…A frequent synonym of this disease is "cryoglobulinemic vasculitis", a term that focuses on the typical histo-pathological alterations responsible for muco-cutaneous and visceral involvement. (Agnello, 1995) The term cryoglobulinemia refers to the presence of a single component (monoclonal) or more (polyclonal) immunoglobulins. These immunoglobulins typically precipitate at temperatures below 37°C giving rise to high molecular weight aggregates and re-dissolve on rewarming.…”