Different sites of xenoantigen delivery lead to a virally induced late-onset hepatitis in mice through molecular mimicry

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DOIResolve DOI: http://doi.org/10.1111/j.1478-3231.2011.02600.x
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TypeArticle
Journal titleLiver International
Volume31
Issue9
Pages13061314; # of pages: 9
Subjectautoimmune hepatitis; break of immune tolerance; liver immunology
AbstractBackground: 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 (RecAdV) 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 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.
Publication date
LanguageEnglish
AffiliationNRC Biotechnology Research Institute; National Research Council Canada
Peer reviewedYes
NRC number53178
NPARC number20534548
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Record identifier4d5b0f53-d375-4222-899d-d067f9a2fa53
Record created2012-08-23
Record modified2016-05-09
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