Only NOD mice were susceptible to induction of emAIH, while C57BL/6 and FVB/N mice did not develop chronic AIH after an initial Ad-FTCD infection. This highlights the importance of genetic predisposition for the development of autoimmunity. A strain specificity for development of hepatitis had been reported earlier,[22] but this was usually not linked to genetic predispositions also seen in AIH patients. In fact, the NOD mice are not just developing type I diabetes, but are also developing sialitis, autoimmune neuropathy, and experimental autoimmune encephalitis (EAE) after induction.[23] The clinical coincidence of several autoimmune

diseases in patients supports the idea of common genetic differences predisposing click here for the development of autoimmunity. The basis for this is susceptible genes shared by many patients

with autoimmune diseases, while other genes are rather linked to organ-specific manifestations (e.g., insulin gene with type I diabetes).[24] Lumacaftor To this end it is interesting to note that the strongest genetic link for the development of type 1 diabetes is the unique MHC haplotype I-Ag7 (idd1). This correlates well with the association of HLA DR3/4 in human type 1 diabetes (IDDM1). Interestingly, an HLA DR3/4 identical association was also reported for patients with AIH. In detail, a predisposition of extended HLA-DRB1 alleles like DRB1*0301, DRB1*0401, DRB1*0404, and DRB1*0405 medchemexpress can be found in patients with AIH[25] as well as patients with type 1 diabetes.[26] In addition, non-HLA susceptibility genes like CTLA-4 (IDDM12), CD45, TNF-α, or vitamin D receptor (IDDM34)[27-30] are associated with the development of type I diabetes and were also associated with the development of AIH.[6, 30-34] Taken together, the use of the NOD strain for successful induction of emAIH underlines the importance of these genetic associations for the induction of AIH. Congenic NOD mice will therefore serve as valuable tools to delineate the importance of individual genes for the development of AIH in the future. The genetic predisposition of NOD mice

might also explain the rather rapid development of emAIH at 12 weeks with fibrosis at 30 weeks. Alvarez and coworkers[13] did not see any AIH in C57BL/6 animals at 10 weeks after induction. In fact, they could just observe infiltrates at 8 months. While genetic predisposition is creating a fertile field for the development of autoimmunity, it is clearly not sufficient for disease induction, as NOD mice do not develop emAIH spontaneously. This highlights the importance of environmental factors triggering autoimmunity. In fact, many environmental and especially infectious agents were suggested to induce AIH in humans.[7-9] However, the lag phase between initiation of autoimmunity and diagnosis of the disease makes it difficult to causally relate environmental triggers to the disease initiation.