AChR antibodies show a complex interaction with human skeletal muscle cells in a transcriptomic study

Area of Science:

• Immunology
• Neuroscience
• Molecular Biology

Background:

• Acetylcholine receptor (AChR) antibodies are key pathogenic markers in myasthenia gravis (MG).
• Antibody binding to AChRs impairs neuromuscular junction signaling, leading to receptor degradation or dysfunction.

Purpose of the Study:

• To investigate the transcriptomic effects of AChR antibodies on human myotubes.
• To identify affected pathways, including those related to AChR degradation and trafficking.

Main Methods:

• Bulk RNA sequencing of mature human myotubes exposed to AChR antibodies.
• Analysis of protein-coding RNAs and long non-coding RNAs (lncRNAs).
• Examination of gene networks and pathway enrichment.

Main Results:

• Over 400 genes were differentially expressed following AChR antibody exposure.
• Significant alterations observed in cholesterol metabolism and extracellular matrix organization pathways, linked to AChR trafficking.
• Muscle contraction and cellular homeostasis pathways were also affected independently of AChR trafficking.
• A protein-coding RNA and lncRNA network showed altered expression, with lncRNA MEG3 correlating with cellular homeostasis genes.

Conclusions:

• AChR antibodies induce a robust active response in human skeletal muscle cells.
• These responses involve significant modulation of intra- and extracellular pathways critical for muscle function and homeostasis.