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.

Progress of OX40 and its ligand in lymphoma immunotherapy / 白血病·淋巴瘤

OX40 is a member of the tumor necrosis factor receptor (TNFR) superfamily. In the immune response of the body, OX40 and the OX40 ligand (OX40/OX40L) on the antigen-presenting cell membrane are important co-stimulatory molecules, which can promote the proliferation of T cells. And OX40 also has the dual role of activating and enhancing the T cell immune response. OX40/OX40L is an important target for tumor immunotherapy, and clinical studies of several OX40 agonists are currently underway. This article reviews the immunoregulatory mechanisms of OX40/OX40L and its research progress in lymphoma immunotherapy.

Effects of Different Doses of Rosuvastatin on Serum Levels of sOX40L and MMP-9 in Patients with Acute Coronary Syndrome / 天津医药

Objective To explore effects of different doses of rosuvastatin on serum soluble OX40 ligand (sOX40L), matrix metalloproteinase-9 (MMP-9) in patients with acute coronary syndrome (ACS). Methods Sixty patients with ACS were evenly divided into 20 mg rosuvastatin treatment group (20 mg group) and 10 mg rosuvastatin treatment group (10 mg group). Twenty healthy volunteers were randomly assigned to control group. The serum levels of sOX40L and MMP-9 were measured and analyzed before and after treatment in three groups. Results The levels of sOX40L and MMP-9 before treat-ment were significantly higher in two treatment groups than those in control group (P<0.01). After two-week treatment with rosuvastatin, serum levels of sOX40L and MMP-9 decreased significantly in two treatment groups compared with those of pre-treatment (P<0.01). Moreover, the levels of sOX40L and MMP-9 were significantly lower in 20 mg group than those in 10 mg group after two-week treatment with rosuvastatin (P<0.05). But the levels of sOX40L and MMP-9 were still higher than control group (P<0.01). Conclusion Larger doses of rosuvastatin may decrease the degradation of extraceller matrix of coronary atherosclerotic plaque and inflammatory reaction, stabilize coronary atherosclerotic vulnerable plaque, and play an important role in improving prognosis in patients with ACS.

Expression of OX40/OX40L mRNA in experimental allergic neuritis under influence of Rho-kinase inhibitor / 中华神经科杂志

Objective To study the expression of mRNA of OX40 and OX40L in the sciatic nerve,spleen,peripheral blood mononuclear cells and lymph nodes of EAN under the influence of Rho-kinase inhibitor.Methods All 54 female Lewis rats were divided into 3 groups:the EAN group,the EAN+ Rho-kinase inhibitor group and the complete Freund's adjuvant(CFA)group.The rats were sacrificed at 9,17 and 26 days after immunized.Ox40 and OX40L mRNA were detected by RT-PCR which came from spleens,sciatic nerves,peripheral blood mononuclear cells and lymphonodes.Results In EAN+ Rho-kinase inhibitor group,the mRNA expression of OX40 were 0.266±0.031,0.298±0.024 and 0.113±0.018 at 9.17 and 26 days in the sciatic nerve,the expression were 0.453±0.030,0.496±0.100 and 0.220±0.016 in the lymph nodes.The mRNA expression of OX40L were 0.247±0.018.0.298±0.026 and 0.165±0.013 in the sciatic nerve,the expression were 0.283±0.027,0.306±0.011 and 0.161±0.012 in the lymph nodes.The mRNA expression of OX40 and OX40L in EAN+Rho-kinase inhibitor group was lower than EAN group at the three time points(t=2.24-4.89,P＜0.05),and the demyelination and inflammation cells infiltrating were ameliorated in spinal nerve.CFA group didn't show any clinical manifestation.Conclusion Rho-kinase inhibitor may ameliorate tlIe development of EAN through inhabiting the OX40 and OX40L activation.