Hepatitis C and D, retroviruses and autoimmune manifestations

Chronic infections with hepatitis C virus (HCV) are associated with various autoimmune manifestations, i.e. mixed cryoglobulinemia, membranoproliferative glomerulonephritis, autoimmune thyroid diseases, sporadic porphyria cutanea tarda and B cell lymphoma. Since exacerbation of hepatitis occurs in 5-10% of HCV patients receiving interferon-alpha treatment and may be successfully treated by immunosuppression afterwards, hepatitis C was also suspected to be associated with autoimmune hepatitis. LKM3 autoantibodies in chronic hepatitis D virus (HDV) infection and epitope recognition are discussed. Lately, endogenous and exogenous retroviruses have been investigated for the induction of autoimmune diseases. Human A type retroviral particles (HIAP), reverse transcriptase activity and anti-HIAP autoantibodies were detected in patients with Sjögren's syndrome. Anti-HIAP and anti-HIV p24 autoantibodies are seen in systemic lupus erythematosus, primary biliary cirrhosis and multiple sclerosis. Multiple sclerosis was even associated with a new human retrovirus called multiple sclerosis associated retrovirus (MSRV). In diabetes long terminal repeats (LTR) were detected in the HLA DQB1 locus, which was shown to associate with an increased risk of diabetes. A second retrovirus called IDDMK(1,2)22 was reported to code for a superantigen, which was implicated as a potential cause of diabetes. This hypothesis, however, was challenged repeatedly. Until now it is unknown whether endogenous retroviruses are aetiological agents of autoimmune diseases or an epiphenomenon, induced by coinfecting viruses (e.g. herpes viruses) and inflammatory processes.