The Clinical Significance And The Expression Of Negative Costimulatory Molecule PD-1 And Its Ligand PD-L1 In Peripheral Blood Of Myasthenia Gravis Patients

Objective: To investigate the expression of negative costimulator molecule PD-1 and its ligand PD-L1 in the peripheral blood of patients with MG and their functions in the pathogenesis of MG,and analyze the correlation between the expression of PD-1 and PD-L1 and the severity of MG,the effect of immunotherapy on PD-1 and PD-L1,and explore the immunological significance of PD-1/PD-L1 molecular signaling pathway in MG.Methods: Thirty MG patients,admitted to the Department of Neurology,the First Hospital of Jilin University,from 2017.1 to 2017.12,were enrolled in our study.All MG patients were not treated with any immunomodulators(including glucocorticoids)and had no other autoimmune diseases.The age and sex of thirty healthy people matched with the MG patients.The subjects had no history of infectious and autoimmune diseases.Blood samples of patients and healthy people were collected.The quantitative myasthenia gravis score(QMGs)was used to evaluate the condition of patients with MG.Osserman clinical classification was finished according to the severity of the disease.Patients were divided into thymoma group and non thymoma group according to thymic pathology.The expression of PD-1 on CD4+ T cells and the expression of PD-L1 on CD14+ monocytes in peripheral blood obtained from MG patients and healthy controls were measured by flow cytometry.Results: 1.Thirty MG patients,age from 18 to 83 years old,19 females and 11 males were included in the MG group.There were 9 patients with early-onset myasthenia gravis and 21 patients with late-onset myasthenia gravis.According to the osserman classification,they were divided into I(n = 3),IIa(n = 7),IIb(n = 13),III(n = 7).According to thymic pathology,MG patients were divided into non-thymoma group(n = 20)and thymoma group(n = 10).According to the symptoms of MG patients,they were divided into crisis group(n = 7)and non-crisis group(n = 23).Relative indexes are compared before and after 1mg/kg.d prednisone intervention in 15 patients with MG for 3 months.2.The expression of PD-1 on CD4+T lymphocytes in peripheral blood of MG patients was sinificantly upregulated when compared to healthy controls(p = 0.048,p < 0.05).The positive expression of PD-L1 on CD14+ monocytes in peripheral blood of MG patients was significantly elevated when compared to healthy controls(p = 0.038,p < 0.05).3.There was no significant difference in the percentage of positive expression of PD-1 on CD4+T lymphocytes before and after glucocorticoid therapy.The positive expression of PD-L1 on CD14+ monocytes after glucocorticoid therapy was lower than that before treatment,but there was no significant difference(p > 0.05).4.The expression of PD-1 and its ligand PD-L1 was not related to age,sex,the clinical classification of MG,thymic pathology and QMGs.Conclusion: The expression of PD-1 on CD4+T lymphocytes and the expression of PD-L1 on CD14+ monocytes in patients with MG was significantly higher than that in healthy controls,suggesting that PD-1/PD-L1 signaling pathway may play a regulatory role in the pathogenesis of myasthenia gravis;short-term glucocorticoid therapy has no effect on PD-1/ PD-L1 signaling pathway.