Expression and significance of OX40/OX40L in peripheral blood of patients with autoimmune hepatitis, primary biliary cholangitis, and their overlap syndrome / 临床肝胆病杂志

ObjectiveTo investigate the expression and clinical significance of OX40/OX40L (CD134/CD134L) in CD4+ T cells, CD8+ T cells, monocytes, and B lymphocytes in peripheral blood of patients with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and their overlap syndrome before and after standardized treatment. MethodsA total of 74 patients with AIH, PBC, and their overlap syndrome who were diagnosed in Subei People’s Hospital of Jiangsu from August 2015 to August 2019 were enrolled, and according to related diagnostic criteria, they were divided into AIH group (group A) with 29 patients, PBC group (group P) with 26 patients, and overlap syndrome group (group C) with 19 patients. A healthy control group with 30 individuals was also established. Peripheral blood samples were collected before and after standardized treatment to measure the expression of OX40/OX40L on the surface of peripheral blood cells by immunofluorescence flow cytometry, and the expression of OX40/OX40L was compared before and after treatment and between the three groups and the healthy control group to investigate its clinical significance. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the paired t-test was used for comparison of paired samples between two groups. ResultsThere were no significant differences in sex composition and age composition between the three groups (P＞0.05). Before treatment, the positive rate of OX40 in peripheral blood CD4+ T cells gradually increased in groups A, P, and C, and groups A, P, and C had a significantly higher positive rate of OX40 than the control group (14.80%±4.99%/17.11%±2.71%/25.18%±5.55% vs 6.67%±2.26%, F=14.823, P＜0.001); groups A, P, and C had a significantly higher positive rate of OX40 in CD8+ T cells than the control group (4.86%±1.54%/6.40%±1.88%/7.33%±2.12% vs 4.09%±2.69%, F=5.486, P＜0.001); the positive rate of OX40L in CD14+ monocytes was 19.84%±6.11% in group A, 21.17%±4.35% in group P, 29.13%±6.32% in group C, and 4.86%±2.34% in the control group, and there was a significant difference between groups (F=17004, P＜0.001); the positive rate of OX40L in CD19+ B cells was 17.62%±3.86% in group A, 14.75%±4.32% in group P, 1013%±2.56% in group C, and 4.50%±1.38% in the control group, showing a trend of gradual reduction, and groups A, P, and C had a significantly higher positive rate than the control group (F=12.221, P＜0.001). After treatment, the positive rate of OX40 in CD8+ T cells decreased significantly to a similar level as the control group, and there was no significant difference between groups (F=0731, P=0.538). For the other three types of cells, although there were varying degrees of reduction in the positive rate of OX40/OX40L after treatment, groups A, P, and C still had a significantly higher positive rate than the control group; in CD4+ T cells, the positive rate of OX40 was 11.00%±1.98% in group A, 13.72%±1.03% in group P, 19.72%±3.47% in group C, and 6.67%±2.26% in the control group, and groups A, P, and C had a significantly higher positive rate than the control group (F=11.365, P＜0.001); in CD14+ monocytes, the positive rate of OX40L was 11.82%±2.23% in group A, 15.19%±4.42% in group P, 24.51%±4.09% in group C, and 4.86%±2.34% in the control group, and groups A, P, and C had a significantly higher positive rate than the control group (F=13748, P＜0.001); in CD19+ B cells, the positive rate of OX40L was 9.09%±3.25% in group A, 6.81%±2.20% in group P, 748%±2.85% in group C, and 4.50%±1.38% in the control group, and groups A, P, and C had a significantly higher positive rate than the control group (F=8.052, P＜0.001). Groups A, P, and C had significant reductions in the expression of OX40/OX40L in peripheral blood CD4+ T cells, CD8+ T cells, CD14+ monocytes, and CD19+ B lymphocytes after treatment (all P＜0.05). ConclusionThe expression of OX40/OX40L in peripheral blood increases in patients with AIH, PBC, and their overlap syndrome and decreases after treatment, indicating that the OX40/OX40L pathway is involved in the pathogenesis of the above diseases, and the role of OX40 on the surface of CD8+ T cells may better reflect the treatment outcome.

Immunological mechanism of Treg/Th17 and Th1/Th2 balance in autoimmune hepatitis and new targets for diagnosis and treatment / 临床肝胆病杂志

Autoimmune hepatitis (AIH) is a chronic autoimmune disease in the liver, with major clinical manifestations of positive autoantibody, abnormal elevation of aminotransferases, and hypergammaglobulinemia. Current studies have shown that regulatory T (Treg)/T helper 17 (Th17) and T helper 1 (Th1)/T helper 2 (Th2) imbalance is one of the mechanisms of the development and progression of AIH. OX40 (also known as CD134, TNFRSF4, or ACT35) and its ligand OX40L are members of the tumor necrosis factor family, and they participate in immune response as co-stimulators of T cell activation and can regulate Treg/Th17 and Th1/Th2 balance, thus affecting the progression of various autoimmune diseases. However, there are few reports on the role of OX40 and OX40L in AIH. With reference to related articles, this article reviews the role of Treg/Th17 and Th1/Th2 balance in AIH and the potential association between OX40/OX40L (new targets for immunological diagnosis and treatment) and AIH.