Evaluation of the role of auto-inflammatory and autoimmune mechanisms in the pathogenesis of autoimmune cholestatic liver diseases through serum cytokine release and TLR 4-6 levels

Primary biliary cholangitis (PBC) is the most frequent autoimmune cholestatic liver disease. Patients have mostly positivity for AMA autoantibodies. NK cells damage the intraepithelial biliary epithelial cells directly or indirectly through cytokines. However, autoantibodies are not diagnostic, nor has their association with prognosis been demonstrated. Although PBC is defined as an autoimmune disease, immunosuppressive drugs used in other autoimmune diseases cannot be used in its treatment. Therefore, it is thought that the pathogenesis of PBC is different from autoimmune pathogenesis. In our study, we aimed to compare the cytokine and TLR levels of PBC with autoinflamatory pathogenesis (Celiac disease: CD) and autoimmune pathogenesis (autoimmune hepatitis: AIH). The serum levels of IL 1, 2, 4, 6, 10, 12, 13, 17, 23, TNF α, IFN γ, TGF β and TLR 4-6 of all patient groups were analyzed by ELISA and flow cytometry method, similarities and differences between groups were evaluated. Statistical analysis was performed using the Kruskal-Wallis and Mann-Whitney U test. For analysis of categorical data, appropriate Chi-square tests or Fisher's exact test were used. Compared to patients with PBC and CD, TNF-α, IFN-γ, TGF-β1, IL-1β, IL-6, IL-10, IL-12p70, IL-17a, IL-23, and TLR 4 levels were found to be elevated in AIH patients. These parameters were the lowest in PBC patients and showed moderate decreases in CD patients. Compared to CD and AIH patients, IL-2 levels were the lowest and IL-13 levels were the highest in PBC patients. Compared to PBC and AIH patients, IL-4 levels were observed to be the highest in CD patients. Compared to the control group, TLR 6 levels showed statistically significant differences among all patient groups. Our study sheds light on future research on the pathogenesis of PBC to discover novel diagnostic and therapeutic markers, and potential therapy stratejies.