Serum Pentaxin 3 (PTX3) Promotes NLRP3 Inflammasome and Pyroptosis in Patients with Up-Regulated Myasthenia Gravis

Abstract

Background: Myasthenia gravis (MG) is an autoantibodies-mediated autoimmune disease with the complications of neuromuscular junction transmission. In this study, we aimed to investigate the molecular regulatory roles of pentaxin 3 (PTX3) in patients and in animal model with MG and to explore its underlying mechanism. Methods: Patients with MG were identified and enrolled at our designated hospital and animal model was utilized for the proposed study. Enzyme-linked immunosorbent assay (ELISA) kit were used to quantify the IL-1β, IL-6, INF-γ, IL-17, TNF-α, anti-TAChR IgG/IgG1/IgG2b/IgG2c levels. Results: Serum PTX3 expression level in patients with MG was up-regulated as compared to normal. Furthermore, we found increased expression level of mRNA and protein product of PTX3 in the mice with MG. PTX3 promoted inflammation, pyroptosis in patients as well as in the MG mouse model. In addition, PTX3 induced the STAT3/NLRP3 inflammasome and promoted gene synthesis of STAT3. We found that METTL3-mediated m6A modification decreases PTX3 stability. Conclusions: Our study suggests that the PTX3 is associated with the enhancement of inflammation and pyroptosis through regulating the STAT3/NLRP3 inflammasome signaling pathway at the early stage of the disease. The pro-inflammatory PTX3 facilitates the development of MG and it can be used as a potantial MG-associated diagnostic biomarker for MG.

Keywords

• myasthenia gravis
• nlrp3
• inflammasome
• ptx3
• neuromuscular disease