Genetic factors and gene polymorphisms leading to the onset of autoimmune response in autoimmune hepatitis (AIH) are still not full elucidated. Since the CTLA-4 molecule is a key modulator of the lymphocytes responses we hypothezied that deficiencies or mutations in the gene encoding CTLA4 protein may be involved in AIH susceptibility and trigger the autoimmune response. We investigated 3 distinct polymorphic sites (+49A > G, CT60 G > A and –318C > T) of the CTLA4 gene in 50 AIH patients and 100 healthy controls using the KASP genotyping technology. A significant positive association with AIH susceptibility was found for the GG genotype in +49 position of the CTLA4 gene which was significantly higher in AIH patients compared to controls (28% vs 9%, p = 0.003, OR = 3.93 [1.56–9.88]). The CTLA4 A/A genotype in position CT60 was more significantly frequent in controls comparing to AIH patients and could be considered as a protective genotype for the tunisian patients. CTLA4 genotyping in position −318 did not show any statistically significant difference in genotype or allele distribution. The CTLA4 gene polymorphism in position +49 is associated to AIH susceptibility in the Tunisian population. Mutation in the CTLA4 gene may lead to a modification of the CTLA4 protein structure that could have functional relevance in AIH pathogenesis and onset.

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Autoimmune hepatitis (AIH) is a chronic hepatitis of unknown etiology and several proinflammatory cytokines are implicated in its pathogenesis. The association of TNF-α gene polymorphism with AIH onset is not fully elucidated especially in the Tunisian population. The aim of this study was to determine the association of TNF-α (-308 G > A) polymorphism with AIH susceptibility and with TNF-α expression or clinical manifestations of AIH. A total of 50 AIH patients and 150 controls were included. Evaluation of TNF-α polymorphism was performed by ARMS PCR method. A significantly higher frequence of the AA genotype was found in AIH patients compared to controls (34 vs. 8%, p = 0.00002, OR 5.88). The frequency of the A-allele was significantly higher in patients with AIH compared to controls (55 vs. 37.3%, p = 0.002, OR 2.05). The G-allele was significantly more frequent in healthy controls compared to AIH patients [43 vs. 61.3%, p = 0.001, OR 0.47 (0.3-0.75)]. There was a positive correlation between the A/A genotype and a higher serum expression of TNF-α. The TNF*A allele confer susceptibility to AIH in the Tunisian patients and is associated with increased production of TNF-α. Anti-TNF antibodies could be an alternative to the use of corticotherapy and may avoid the exacerbated immune response in AIH.

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