A recent study published in the Journal of Neurochemistry has revealed that a significant increase in ceramides might be involved in the pathogenesis of myasthenia gravis (MG).
The study findings suggest that the elevated C18:0-Cer level positively correlated with all indications, including the disease severity, cytokines, pathogenic immune cells, and down-regulated as the improvement of the condition, suggesting that C18:0-Cer can be a promising marker for predicting and evaluating the disease severity.
Read more about MG therapies
The team recruited 110 patients with MG from the affiliated hospital of Xuzhou medical university from November 2021 to February 2023. Disease severity was evaluated through quantitative MG scores (QMGs), 15-item MG quality of Life, and MG-specific activities of daily living scale, while the plasma ceramides levels were determined through ultra performance liquid chromatography–tandem mass spectrometry.
Moreover, enzyme-linked immunosorbent assay was utilized to determine the concentrations of serum interleukin-1β (IL-1β), IL-17A, IL-21, and IL-6. Finally, the proportions of circulating memory B cells and plasma blasts were identified by flow cytometry assay.
Study results showed that four plasma ceramide levels were higher in patients with MG, while three of them (C16:0-Cer, C18:0-Cer, and C24:0-Cer) were positively associated with QMGs. Moreover, the receiver operating characteristic (ROC) analysis demonstrated that plasma ceramides could differentiate MG from healthy controls (HCs).
“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”, the authors wrote.
Notably, only C18:0-Cer was positively associated with the concentration of serum IL and circulating memory B cells, while the decrease in plasma C18:0-Cer correlated with the clinical improvement of patients with MG. The researchers remarked that multi-center studies with a larger population should be conducted to verify the relationship between ceramides and MG. Furthermore, further in vitro and animal experiments are required to clarify the exact pathway of ceramides in MG.
MG is a rare autoimmune disease caused by plasma cell production of pathogenic antibodies, resulting in acetylcholine transmission dysfunction at the neuromuscular junction. A recent survey has shown that the incidence of MG in China is approx. 0.68/100 000 individuals, with a slightly higher incidence in women and people aged 70–74.
Currently, the primary treatments for MG include glucocorticoids, cholinesterase inhibitors, immunosuppressors, thymectomy, plasma exchange, targeted B lymphocyte therapy, etc. Nonetheless, due to the significant heterogeneity among patients with MG, about 10%–15% don’t respond effectively to the existing therapies called refractory MG.
Ceramides have been assumed to play key roles in membrane homeostasis and several physiological functions. Prior studies have demonstrated that ceramides play a role in the regulation of cytokines secretion and T cells development and can activate the expression and activation of nuclear factor-κB as well as promotes inflammatory response and induce secretion of cytokines such as IL-1β and IL-6.
Reference
Zhang Z, Huang X, Du X, et al. Plasma C18:0-ceramide is a novel potential biomarker for disease severity in myasthenia gravis. J Neurochem. Published online May 9, 2023. doi:10.1111/jnc.15837
