title: Type 2 autoimmune hepatitis murine model: the influence of genetic background in disease development.
abstract: Genetic predisposition is recognized as an important factor for the development of autoimmune hepatitis (AIH). To assess the potential contribution of MHC and non-MHC genes, type 2 AIH was reproduced in three mice strains, taking advantage of their different genetic makeup with regard to MHC and non-MHC genes. Mice (C57BL/6, 129/Sv and BALB/c) were DNA vaccinated with a pCMV-CTLA4-CYP2D6-FTCD plasmid coding for the extracellular region of CTLA-4 and for the antigenic region of the CYP2D6 and FTCD, and with pCMV-IL12. ALT and total IgG levels, liver histology, FACS analysis and liver T-cell cytotoxicity assays were monitored up to 8 months post-injection. C57BL/6 mice showed elevated serum ALT levels, autoantibodies, antigen-specific cytotoxic T-cells and lobular and periportal inflammatory infiltrate. The 129/Sv mice showed slightly elevated ALT levels, sparse liver lobular infiltrate and cytotoxic T-cells. The BALB/c mice showed no liver inflammation. All mice had elevated total serum IgG levels. This murine model of type 2 AIH shows that MHC and non-MHC genes contribute to the susceptibility to autoimmune hepatitis. The understanding of the genetic determinants implicated in AIH development will be a major advance in the study of its pathogenesis and could lead to a better diagnostic approach and preventive strategies.
authors.affiliation: Service de Gastroentérologie et Nutrition, Hôpital Sainte-Justine, 3175 Côte Ste-Catherine, Montréal, Québec, Canada H3T 1C5.
authors.forename: Pascal
authors.initials: P
authors.lastname: Lapierre
authors.forename: Kathie
authors.initials: K
authors.lastname: Béland
authors.forename: Idriss
authors.initials: I
authors.lastname: Djilali-Saiah
authors.forename: Fernando
authors.initials: F
authors.lastname: Alvarez
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000642:Ammonia-Lyases; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies; D001402:B-Lymphocytes / Q000276:immunology; D060908:CTLA-4 Antigen; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D051042:Glutamate Formimidoyltransferase; D019693:Hepatitis, Autoimmune / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D007074:Immunoglobulin G / Q000097:blood; D008285:Major Histocompatibility Complex / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D009097:Multienzyme Complexes / Q000235:genetics / Q000276:immunology; D064251:Multifunctional Enzymes; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D001323:Autoantibodies; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D007074:Immunoglobulin G; D009097:Multienzyme Complexes; D064251:Multifunctional Enzymes; D019389:Cytochrome P-450 CYP2D6; C494850:Ftcd protein, mouse; D051042:Glutamate Formimidoyltransferase; D000410:Alanine Transaminase; D000642:Ammonia-Lyases