Autoimmune hepatitis: evolving concepts.
The liver is continuously exposed to a large antigenic load that includes pathogens, toxins, tumor cells and dietary antigens. A loss of tolerance against its own antigens may result in autoimmune hepatitis (AIH). The current paradigm holds that the disease is the result of self-perpetuating autoimmune process triggered by yet unknown factors (infections, chemicals, drugs) in a genetically susceptible host. To date, several putative hepatocellular surface antigens have been identified: P450-IID6 (recognized by the anti-LKM-1 autoantibodies) a membrane bound asialoglycoprotein receptor (a liver-specific membrane protein), a cytosolic UGA-suppressor tRNA associated protein (recognized by anti-SMA and anti-LP antibodies) and argininosuccinate lysate and formiminotransferase cyclodeaminase (recognized by ant-LC1 antibodies). In contrast to other chronic hepatitides patients with AIH display significant T cell hypereactivity to autologous liver antigens. Tissue injury seems to be mediated by CD4+ or CD8+ T cells and/or by antibody-dependent cell mediated cytotoxicity.
Diamantis
Ioannis
I
Department of Internal Medicine and Division of Rheumatology, Clinical Immunology and Allergy, Medical School, University of Crete, P.O. Box 2208, Heraklion GR-71003, Greece. idiamant@med.uoc.gr
Boumpas
Dimitrios T
DT
D000642:Ammonia-Lyases / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D001123:Argininosuccinate Lyase / Q000276:immunology; D001189:Aryl Hydrocarbon Hydroxylases / Q000276:immunology; D037263:Asialoglycoprotein Receptor / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019693:Hepatitis, Autoimmune / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000276:immunology* / Q000473:pathology; D012343:RNA, Transfer / Q000276:immunology
D037263:Asialoglycoprotein Receptor; D001323:Autoantibodies; D001324:Autoantigens; D012343:RNA, Transfer; D001189:Aryl Hydrocarbon Hydroxylases; D000642:Ammonia-Lyases; C020148:formiminotetrahydrofolate cyclodeaminase; D001123:Argininosuccinate Lyase