title: Different sites of xenoantigen delivery lead to a virally induced late-onset hepatitis in mice through molecular mimicry.
abstract: BACKGROUND
  Epidemiological and laboratory evidences led to the hypothesis that molecular mimicry between viruses and self-proteins could be linked to the onset of autoimmune hepatitis (AIH). Hepatotropic viruses could be good candidates, as a pro-inflammatory environment may facilitate the development of AIH.
  
  
  OBJECTIVE
  The aims of this study were to test a virus ability to induce an AIH through molecular mimicry and the influence of hepatic inflammation in this process.
  
  
  METHODS
  C57BL/6 mice were injected i.v. or i.m. with recombinant adenoviral vectors (RecAdV) encoding for human type 2 AIH antigens to target xenoantigens expression in the liver and to create a transient hepatitis (i.v.) or for 'peripheral' xenoantigens expression (i.m.). Liver injury and B-cell response were evaluated.
  
  
  RESULTS
  Late-onset hepatitis was observed 8 months after i.v. or i.m. RecAdV injections, despite presence or absence of an initial transient hepatitis. Intensity of B-cell response was similar for both type of injections, but the Ig isotypes produced were different. B-cell autoimmune response spread to several liver proteins.
  
  
  CONCLUSIONS
  Liver autoimmune response can be initiated using molecular mimicry over a long period of time, validating the hit-and-run hypothesis. Initial liver inflammatory injury is neither necessary, nor detrimental to the development of AIH. These results highlight the significance of initial events on the pathogenesis of autoimmune liver injury.
authors.affiliation: Division of Gastroenterology, Hepatology, Nutrition, CHU Sainte-Justine, Montréal, QC, Canada.
authors.forename: Chantal
authors.initials: C
authors.lastname: Piché
authors.forename: Kathie
authors.initials: K
authors.lastname: Béland
authors.forename: Pascal
authors.initials: P
authors.lastname: Lapierre
authors.forename: Bernard
authors.initials: B
authors.lastname: Massie
authors.forename: Fernando
authors.initials: F
authors.lastname: Alvarez
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000642:Ammonia-Lyases / Q000235:genetics / Q000276:immunology; D000818:Animals; D015478:Antigens, Heterophile / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D060908:CTLA-4 Antigen / Q000235:genetics / Q000276:immunology; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000276:immunology; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D051042:Glutamate Formimidoyltransferase / Q000235:genetics / Q000276:immunology; D019693:Hepatitis, Autoimmune / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008099:Liver / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018716:Molecular Mimicry; D064251:Multifunctional Enzymes; D018417:Th1 Cells / Q000276:immunology / Q000821:virology; D018418:Th2 Cells / Q000276:immunology / Q000821:virology; D013997:Time Factors
chemical_list: D015478:Antigens, Heterophile; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D064251:Multifunctional Enzymes; D019389:Cytochrome P-450 CYP2D6; C494848:FTCD protein, human; D051042:Glutamate Formimidoyltransferase; D000642:Ammonia-Lyases