CONTRIBUTION OF CLASS II GENES TO THE EXPRESSION OF AUTOIMMUNITY IN CHRONIC HEPATITIS C.
MN Vazquez-Garcia 1,2, D Kershenobich 3, C. Alaez 1, G de la Rosa 1, A Vázquez 1, A Cárdenas 3, Gorodezky.C 1. 1 Dept of Immunogenetics, INDRE, SSA., 2 PMBM-CINVESTAV.IPN., 3 Dept of Gastroenterology, INNSZ, SSA Mexico City, MEXICO.
It is estimated that 175 million people worldwide are infected with HCV; of them, 80% will develop a chronic disease with or without autoimmunity. Patients may have different types of autoantibodies and/or distinct forms of autoimmune associated disorders after HCV infection. Among them, mixed cryoglobulinemia, lichen planus or thyroiditis and some times rheumatoid arthritis and systemic lupus erythematosous have been described. It is clear that T CD4+ cells and TH1-type cytokines are involved in virus clearing, but nothing is known about the genetic mechanism of chronicity, neither on the possible genetic control of autoantibody synthesis in these patients. The aim of this work was to analyze if class II genes contribute to the expression of autoimmunity in chronic hepatitis C and the possible contribution of MHC alleles to the synthesis of autoantibodies. Class II DNA typing was done in a group of 33 patients diagnosed according to the international criteria and in 170 healthy, unrelated individuals, all of them Mexican Mestizos. DNA typing of DRB1, DQA1 and DQB1 alleles was done by PCR-SSOP according to the 12th IHW protocols. Antinuclear (ANA), antimitochondrial (AMA) and anti-smooth muscle (SMA) autoantibodies where done by indirect immunofluorescence on Hep-G2 cells. Of the total patients, 79% were females and 58% developed an autoimmune disorder, 58% (11/19) had autoantibodies (AMA and/or SMA). DRB1*0301 was found associated with chronic hepatitis C (chi2=4.3, OR=4.1, pc=0.002, 1.1-14.3). An interesting finding was the presence on Is gene that controls the synthesis of SMA which it linked to DQB1*0201 (chi2=5.4, pc=0.002), since 88%of the patients with the allele do not produce SMA. This data confirm, as shown for different autoimmune diseases, that DQB locus is involved in the genetic control of autoantibody production. Moreover DRB1*0301 is partly responsible of the chronic process unchained by HCV.