| First Author | Yang CY | Year | 2012 |
| Journal | Clin Exp Immunol | Volume | 168 |
| Issue | 3 | Pages | 261-7 |
| PubMed ID | 22519587 | Mgi Jnum | J:184866 |
| Mgi Id | MGI:5426485 | Doi | 10.1111/j.1365-2249.2012.04577.x |
| Citation | Yang CY, et al. (2012) Epitope-specific anti-nuclear antibodies are expressed in a mouse model of primary biliary cirrhosis and are cytokine-dependent. Clin Exp Immunol 168(3):261-7 |
| abstractText | Although the hallmark of primary biliary cirrhosis (PBC) is the presence of anti-mitochondrial antibodies (AMA), a significant number of patients have anti-nuclear antibodies (ANA) directed primarily against two nuclear proteins, gp210 and sp100. In PBC, there are considerable data on the specificity of these anti-nuclear antibodies as well as suggestive evidence that antibodies to gp210 predict a poor outcome. However, a further understanding of the significance of these autoantibodies has been hampered by limitations in accessing human subjects in a preclinical or early asymptomatic stage. To overcome this limitation, we have taken advantage of transgenic mice with abrogated transforming growth factor-beta signalling in T cells (dnTGF-betaRII) that develop histological features of PBC as well as the same AMA specificity. We studied these mice for serum ANA, including specific autoantibodies against gp210 and sp100. We further examined sera from dnTGF-betaRII mice with concurrent deletions of the genes encoding interleukin (IL)-12p35, IL-12p40, IL-23p19, IL-17, IL-6, interferon (IFN)-gamma or tumour necrosis factor (TNF)-alpha. Sera from all the dnTGF-betaRII mouse lines contained antibodies against gp210 and sp100. Of significance, mice with germline deletions of the genes encoding IL-12p40, IL-23p19, IL-17, IL-6 and TNF-alpha had significantly lower titres of anti-gp210 antibodies. These results provide a platform to dissect the mechanisms of gp210 and sp100 autoantibody production in dnTGF-betaRII mice as well as to study the possible role of ANA in the pathophysiology of PBC. |
