AUTOANTIBODIES AGAINST THE HUMAN ASIALOGLYCOPROTEIN RECEPTOR - EFFECTS OF THERAPY IN AUTOIMMUNE AND VIRUS-INDUCED CHRONIC ACTIVE HEPATITIS

The hepatic asialoglycoprotein receptor (ASGPR) was recently identifie d as a target antigen for both humoral and cellular immune response in inflammatory liver diseases. Thereby anti-ASGPR autoantibodies direct ed against human substrate were closely associated with autoimmune chr onic active hepatitis. The present study compares the occurrence, tite r and immunoglobulin classification of anti-human(h-)-ASGPR antibodies in 23 patients with newly diagnosed autoimmune chronic hepatitis befo re and after initiation of immunosuppressive therapy to 22 patients wi th autoimmune hepatitis in remission. Additionally, 1-year follow-up e xaminations of 42 patients with HBsAg-positive chronic hepatitis and o f 32 patients with chronic hepatitis C receiving recombinant interfero n-alpha were included. Nineteen of 23 patients with newly diagnosed an d 9/22 with autoimmune hepatitis in remission, 5/42 with untreated chr onic hepatitis B and 5/32 patients with chronic hepatitis C exhibited anti-h-ASGPR at the beginning of the study. In autoimmune hepatitis an ti-h-ASGPR were found in higher titers (median > 1:1000) than in viral hepatitis (maximum 1:400). After initiation of immunosuppressive ther apy in autoimmune hepatitis anti-h-ASGPR decreased sharply. Eight of 1 9 patients eliminated anti-h-ASGPR within 18 months in contrast to 11 patients with persistent anti-h-ASGPR titer over 18 months and longer. Anti-h-ASGPR with maximum titer of 1:600 were detected in 5 patients with chronic hepatitis B (transiently in 4/5 patients) and in 2 patien ts with chronic hepatitis C during interferon-alpha. Anti-h-ASGPR were from immunoglobulin classes IgG and IgM in cases with untreated autoi mmune hepatitis and chronic hepatitis B and C exhibiting mainly IgG2-s ubclass in autoimmune and IgG4 in viral hepatitis. Lower titer (up to 1:400) anti-h-ASGPR in autoimmune hepatitis were exclusively from IgG- type in contrast to viral hepatitis, respectively, where both IgG and IgM-class anti-h-ASGPR were found despite lower titer values. Thus, ou r results clearly indicate different patterns of anti-h-ASGPR occurren ce, titer and immunoglobulin classes in patients with either autoimmun e or viral hepatitis, respectively. This suggests different pathways o f induction and perpetuation of autoantibody formation in inflammatory liver diseases in man.