Serum from patients with acetylcholine receptor antibody–positive myasthenia gravis triggers pathogenic changes in human myotube cells

Background

Some patients with myasthenia gravis (MG) are refractory to available treatments, highlighting the need to further understand the pathogenesis of the disease. This study aimed to determine whether components in the serum from patients with acetylcholine receptor (AChR) antibody–positive MG affect myotubes, to explore their possible role in disease pathogenesis beyond the inhibition of acetylcholine signal transmission.

Methods

Serum was collected from 14 patients with AChR antibody–positive MG. The differentiated human myotubes were stimulated with 10% serum from healthy controls or patients with MG. After 24 h, ribonucleic acid extraction/sequencing was performed, and differentially expressed genes (DEGs) were extracted. Pathway analysis was completed using DEGs that were downregulated by stimulation with serum from patients with MG. Expression of genes important for muscle contraction was measured and myotube diameter was determined by immunostaining.

Results

Approximately 1200 DEGs were extracted by comparing gene expression in cultured human myotube cells stimulated with serum from healthy controls and patients with MG. Gene ontology terms linked with muscle function were suppressed in myotube cells stimulated with patient serum. Suppression of pathways associated with muscle atrophy/weakness, decreased expression of genes associated with muscle contraction, and smaller myotube diameter were confirmed in myotube cells stimulated with serum from patients versus healthy controls.

Conclusion

Factors other than acetylcholine signal transmission inhibition may contribute to the pathogenesis of AChR antibody–positive MG. Further research is needed to clarify the pathways involved, potentially leading to more tailored pharmacotherapies.