Autoantibodies against the human asialoglycoprotein receptor: effects of therapy in autoimmune and virus-induced chronic active hepatitis.
The hepatic asialoglycoprotein receptor (ASGPR) was recently identified as a target antigen for both humoral and cellular immune response in inflammatory liver diseases. Thereby anti-ASGPR autoantibodies directed against human substrate were closely associated with autoimmune chronic active hepatitis. The present study compares the occurrence, titer and immunoglobulin classification of anti-human(h-)-ASGPR antibodies in 23 patients with newly diagnosed autoimmune chronic hepatitis before and after initiation of immunosuppressive therapy to 22 patients with autoimmune hepatitis in remission. Additionally, 1-year follow-up examinations of 42 patients with HBsAg-positive chronic hepatitis and of 32 patients with chronic hepatitis C receiving recombinant interferon-alpha were included. Nineteen of 23 patients with newly diagnosed and 9/22 with autoimmune hepatitis in remission, 5/42 with untreated chronic hepatitis B and 5/32 patients with chronic hepatitis C exhibited anti-h-ASGPR at the beginning of the study. In autoimmune hepatitis anti-h-ASGPR were found in higher titers (median > 1:1000) than in viral hepatitis (maximum 1:400). After initiation of immunosuppressive therapy in autoimmune hepatitis anti-h-ASGPR decreased sharply. Eight of 19 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 patients with chronic hepatitis C during interferon-alpha. Anti-h-ASGPR were from immunoglobulin classes IgG and IgM in cases with untreated autoimmune hepatitis and chronic hepatitis B and C exhibiting mainly IgG2-subclass in autoimmune and IgG4 in viral hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)
Treichel
U
U
1st Department of Internal Medicine, University of Mainz, Germany.
Gerken
G
G
Rossol
S
S
Rotthauwe
H W
HW
Meyer zum Büschenfelde
K H
KH
Poralla
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000628:therapy; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006521:Hepatitis, Chronic / Q000276:immunology* / Q000628:therapy; D006525:Hepatitis, Viral, Human / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000276:immunology*
D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D001323:Autoantibodies; D011956:Receptors, Cell Surface