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Different sites of xenoantigen delivery lead to a virally induced late‐onset hepatitis in mice through molecular mimicry
Author(s) -
Piché Chantal,
Béland Kathie,
Lapierre Pascal,
Massie Bernard,
Alvarez Fernando
Publication year - 2011
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2011.02600.x
Subject(s) - molecular mimicry , immunology , autoimmune hepatitis , liver injury , pathogenesis , hepatitis , medicine , antigen , virus , liver cell , virology , biology
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 . Aims: 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 IV or IM with recombinant adenoviral vectors ( R ec AdV ) encoding for human type 2 AIH antigens to target xenoantigens expression in the liver and to create a transient hepatitis ( IV ) or for ‘peripheral’ xenoantigens expression ( IM ). Liver injury and B ‐cell response were evaluated. Results: Late‐onset hepatitis was observed 8 months after IV or IM R ec AdV 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.