Clinical Significance of OX40 and OX40 Ligand in the Peripheral Blood of Patients with Myasthenia Gravis

• Published in: Journal of immunology research 2022-02, Vol.2022, p.4337399-17
• Main Authors: Zhou, Xiaoling, Wang, Xiaoyuan, Gu, Yanzheng, Chen, Lan, Shen, Yueping, Tian, Jingluan, Shujun, Chen, Wang, Mingyuan, Duan, Xiaoyu, Gao, Hanqing, Ji, Xiaopei, Fang, Qi, Zhang, Xueguang, Xue, Qun
• Format: Article
• Language: English
• Subjects: Acetylcholine receptors; Antibodies; Autoimmune diseases; CD14 antigen; CD19 antigen; CD4 antigen; Clinical significance; Correlation analysis; Disease; Enzyme-linked immunosorbent assay; Flow cytometry; Germinal centers; Glycoproteins; Humans; Immunology; Immunosuppressive agents; Ligands; Lymphocytes; Lymphocytes B; Lymphocytes T; Monocytes; Myasthenia; Myasthenia gravis; Myasthenia Gravis - diagnosis; Myasthenia Gravis - metabolism; Neoplasm Recurrence, Local; Neuromuscular junctions; OX40 Ligand - blood; OX40 Ligand - metabolism; Ox40L protein; Pathogenesis; Patients; Peripheral blood; Plasma; Plasma levels; Receptors, OX40 - blood; Receptors, OX40 - metabolism; Remission; Remission (Medicine); Retrospective Studies; Steroids; Task forces; Thymus; Tumor necrosis factor; Tumor necrosis factor-TNF
• ISSN: 2314-8861; 2314-7156
• DOI: 10.1155/2022/4337399

Background. A previous study on thymomas in myasthenia gravis (MG) patients indicated that OX40 expression may be upregulated in thymic tissues adjacent to germinal centers (GCs) and thymomas, and OX40 may interact with OX40L in GCs to enhance anti-acetylcholine receptor antibody production. However, little is known about the clinical significance of the expression of OX40 and OX40L in the peripheral blood of patients with MG. We aimed to characterize the expression of membrane-bound and soluble OX40 and OX40L in the peripheral blood of patients with MG and to identify their clinical significance. Methods. For membrane molecules, we collected peripheral blood (PB) from 39 MG patients at baseline, 22 patients in relapse, and 42 patients in remission, as well as from 36 healthy participants as controls. For soluble molecules, plasma from 37 MG patients at baseline, 34 patients in relapse, and 30 patients in remission, as well as plasma from 36 healthy controls (HC), was retrospectively collected from the sample bank of the First Hospital of Soochow University. The expression of membrane-bound OX40 and OX40L (mOX40 and mOX40L) by immune cells was measured using flow cytometry. Plasma levels of soluble OX40 and OX40L (sOX40 and sOX40L) were measured by ELISA. Results. (1) The expression of OX40 on CD4+ T cells and that of OX40L on B cells and monocytes were significantly increased, and the levels of sOX40 were significantly decreased in MG patients at baseline compared with HC, while the expression of sOX40L was not significantly different between the two groups. (2) Dynamic observation of the molecules showed significantly higher expression of OX40 on CD4+ T cells and higher levels of sOX40 in MG patients in relapse than in MG patients at baseline and MG patients in remission. Furthermore, the expression levels of sOX40 were significantly elevated in MG patients in remission compared with MG patients at baseline, and the expression of sOX40L was significantly lower in MG patients in remission than in MG patients at baseline and MG patients in relapse. (3) Plasma levels of sOX40 and sOX40L were significantly decreased in 13 patients with relapsed MG after immunosuppressive treatment compared with those before treatment. (4) Correlation analysis showed that the expression of OX40 on CD4+ T cells in patients with relapsed MG was positively correlated with the concentration of acetylcholine receptor antibodies (AchR-Ab), whereas the expression of OX40L on CD19+ B