Different sites of xenoantigen delivery lead to a virally induced late-onset hepatitis in mice through molecular mimicry
Article first published online: 4 AUG 2011
© 2011 John Wiley & Sons A/S
Volume 31, Issue 9, pages 1306–1314, October 2011
How to Cite
Piché, C., Béland, K., Lapierre, P., Massie, B. and Alvarez, F. (2011), Different sites of xenoantigen delivery lead to a virally induced late-onset hepatitis in mice through molecular mimicry. Liver International, 31: 1306–1314. doi: 10.1111/j.1478-3231.2011.02600.x
- Issue published online: 6 SEP 2011
- Article first published online: 4 AUG 2011
- Manuscript Accepted: 24 JUN 2011
- Manuscript Received: 6 JAN 2011
- Canadian Institutes of Health Research (CIHR). Grant Number: MOP-86506
- autoimmune hepatitis;
- break of immune tolerance;
- liver immunology
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.
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.
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.
Late-onset hepatitis was observed 8 months after IV or IMRecAdV 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.
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.