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Journal of Autoimmune Diseases

, 1:2

First Online: 15 October 2004Received: 14 December 2003Accepted: 15 October 2004


Autoimmune hepatitis AIH is a chronic necroinflammatory disease of the liver characterized by hypergammaglobulinemia, characteristic autoantibodies, association with HLA DR3 or DR4 and a favorable response to immunosuppressive treatment. The etiology is unknown. The detection of non-organ and liver-related autoantibodies remains the hallmark for the diagnosis of the disease in the absence of viral, metabolic, genetic, and toxic etiology of chronic hepatitis or hepatic injury. The current classification of AIH and the several autoantibodies-target-autoantigens found in this disease are reported. Current aspects on the significance of these markers in the differential diagnosis and the study of pathogenesis of AIH are also stated. AIH is subdivided into two major types; AIH type 1 AIH-1 and type 2 AIH-2. AIH-1 is characterized by the detection of smooth muscle autoantibodies SMA and-or antinuclear antibodies ANA. Determination of antineutrophil cytoplasmic autoantibodies ANCA, antibodies against the asialoglycoprotein receptor anti-ASGP-R and antibodies against to soluble liver antigens or liver-pancreas anti-SLA-LP may be useful for the identification of patients who are seronegative for ANA-SMA. AIH-2 is characterized by the presence of specific autoantibodies against liver and kidney microsomal antigens anti-LKM type 1 or infrequently anti-LKM type 3 and-or autoantibodies against liver cytosol 1 antigen anti-LC1. Anti-LKM-1 and anti-LKM-3 autoantibodies are also detected in some patients with chronic hepatitis C HCV and chronic hepatitis D HDV. Cytochrome P450 2D6 CYP2D6 has been documented as the major target-autoantigen of anti-LKM-1 autoantibodies in both AIH-2 and HCV infection. Recent convincing data demonstrated the expression of CYP2D6 on the surface of hepatocytes suggesting a pathogenetic role of anti-LKM-1 autoantibodies for the liver damage. Family 1 of UDP-glycuronosyltransferases has been identified as the target-autoantigen of anti-LKM-3. For these reasons the distinction between AIH and chronic viral hepatitis especially of HCV is of particular importance. Recently, the molecular target of anti-SLA-LP and anti-LC1 autoantibodies were identified as a 50 kDa UGA-suppressor tRNA-associated protein and a liver specific enzyme, the formiminotransferase cyclodeaminase, respectively. Anti-ASGP-R and anti-LC1 autoantibodies appear to correlate closely with disease severity and response to treatment suggesting a pathogenetic role of these autoantibodies for the hepatocellular injury. In general however, autoantibodies should not be used to monitor treatment, predict AIH activity or outcome. Finally, the current aspects on a specific form of AIH that may develop in some patients with a rare genetic syndrome, the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome APECED are also given. Autoantibodies against liver microsomes anti-LM are the specific autoantibodies detected in AIH as a disease component of APECED but also in cases of dihydralazine-induced hepatitis. Cytochrome P450 1A2 has been identified as the target-autoantigen of anti-LM autoantibodies in both APECED-related AIH and dihydralazine-induced hepatitis. The latter may indicate that similar autoimmune pathogenetic mechanisms can lead to liver injury in susceptible individuals irrespective of the primary defect. Characterization of the autoantigen-autoantibody repertoire continues to be an attractive and important tool to get access to the correct diagnosis and to gain insight into the as yet unresolved mystery of how hepatic tolerance is given up and AIH ensues.

KeywordsAntibodies against Liver Cytosol 1 Antigen anti-LC1 Antibodies against Soluble Liver Antigens or Liver Pancreas anti-SLA-LP Antinuclear Antibodies ANA Antineutrophil Cytoplasmic Autoantibodies ANCA Autoimmune Hepatitis Cytochrome P450 2D6 Cytochrome P450 2A6 Cytochrome P450 1A2 Hepatitis C Hepatitis D Liver-Kidney Microsomal Autoantibodies anti-LKM Liver Microsomal Autoantibodies anti-LM Smooth Muscle Autoantibodies SMA Electronic supplementary materialThe online version of this article doi:10.1186-1740-2557-1-2 contains supplementary material, which is available to authorized users.

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Autor: Kalliopi Zachou - Eirini Rigopoulou - George N Dalekos


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