Autoimmune phenomena and hepatitis C virus in lymphoproliferative and connective tissue disorders

Since hepatitis C virus (HCV) infection is frequently detected in patients with lymphoproliferative or autoimmune disorders and since the virus may infect lymphocytes, the question is raised whether malignant transformation and autoimmune manifestations in the presence of HCV are HCV-related or merely fortuitous. A close association has been firmly established between HCV infection and essential type II mixed cryoglobulinemia (ECM), an indolent lymphoproliferative disorder characterized by cryoprecipitable immune-complexes (IC) that may evolve into classical non Hodgkin's lymphomas (NHL) retaining the ability to produce cryoprecipitable rheumatoid factor (RF). It is reasonable to consider HCV as one cofactor in lymphomagenesis, even if the precise pathogenetic relationship between HCV infection, the chronic presence of cryoprecipitable IC and the development of NHL have not been established yet. Several epidemiological studies have documented the ability of chronic HCV infection to favour the production of autoAb. It is not clear why only some patients with HCV infection develop autoAb, nor why the most frequent autoAb detected in HCV-infected subjects are cryoglobulins. Though a high prevalence of anti-HCV has been found in a variety of systemic and organ-specific autoimmune diseases, it is likely that several of these associations are fortuitous with the notable exception of membranoproliferative glomerulonephritis. As HCV can provoke or exacerbate inflammatory signs and cause the production of RF, it is reasonable to suspect that HCV infection may be able to trigger the development of some connective tissue diseases or to exacerbate their clinical course. Nonetheless, it is clinically prudent to conclude that the pathogenetic relationships of Sjogren syndrome, rheumatoid arthritis and polyarthritis with HCV infection are more likely to be regarded as mediated via the intermediate development of ECM.