Plasma C18:0‐ceramide is a novel potential biomarker for disease severity in myasthenia gravis

Abstract

Myasthenia gravis (MG) is an antibody‐mediated autoimmune disorder characterized by fluctuation of fatigue and weakness of muscle. Due to the heterogeneity of the course of MG, available biomarkers for prognostic prediction are urgently needed. Ceramide (Cer) was reported to participate in immune regulation and many autoimmune diseases, but its effects on MG remain undefined. This study aimed to investigate the ceramides expression levels in MG patients and their potential as novel biomarkers of disease severity. Levels of plasma ceramides were determined by ultra performance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS). Severity of disease was assessed by quantitative MG scores (QMGs), MG‐specific activities of daily living scale (MG‐ADLs) and 15‐item MG quality of Life (MG‐QOL15). The concentrations of serum interleukin‐1β (IL‐1β), IL‐6, IL‐17A, and IL‐21 were determined by enzyme‐linked immunosorbent assay (ELISA), and the proportions of circulating memory B cells and plasmablasts were detected by flow‐cytometry assay. Four plasma ceramides levels we studied were detected higher in MG patients. And three of them (C16:0‐Cer, C18:0‐Cer, and C24:0‐Cer) were positively associated with QMGs. In addition, receiver operating characteristic (ROC) analysis suggested that plasma ceramides have a good ability of differentiating MG from HCs. Importantly, only C18:0‐Cer was shown to be positively associated with the concentration of serum IL and circulating memory B cells, and the decrease in plasma C18:0‐Cer paralleled the clinical improvement of patients with MG. All together, our data suggest that ceramides may play an important role in the immunopathological mechanism of MG, and C18:0‐Cer has the potential to be a novel biomarker for disease severity in MG.

Serum amyloid A facilitates expansion of CD4+ T cell and CD19+ B cell subsets implicated in the severity of myasthenia gravis patients

“…We prospectively enrolled 82 AchR-Ab+MG patients including 50 new-onset MG patients and 32 myasthenic crisis (MC) patients, and 27 healthy controls (HC) at the Affiliated Hospital of Xuzhou Medical University and First Hospital of Shijiazhuang, no blinding was performed. The sample size was referred to previous similar studies exploring MG biomarkers (Ge et al, 2023;Li et al, 2022;Uzawa et al, 2020;Zhang et al, 2023). Diagnosis of MG was in accord with international consensus guidance: (1) typical clinical signs of fluctuating fatigue of skeletal muscles; (2) positive response to neostigmine; (3) decremental pattern on repetitive nerve stimulation;…”