Single-cell RNA sequencing reveals cell immune status and dysregulated monocytes in patients with myasthenia gravis

Abstract

Objectives

As an autoimmune disorder, myasthenia gravis (MG) manifests as an autoimmune attack on postsynaptic neuromuscular junction proteins by pathogenic autoantibodies. This immune attack disrupts neurotransmission, resulting in fatigable skeletal muscle weakness with diurnal fluctuation. However, functional cure biomarkers for patients remain limited.

Methods

Peripheral blood collection was performed at three time points in patients with MG: before treatment (Pre), 1 month after treatment (Post) and functional cure (long-term follow-up, LF). Single-cell RNA sequencing was performed. The clinical examination results were collected and summarised.

Results

In general, patients with MG exhibited dynamic changes in immune cell composition and inflammatory features. In particular, monocytes were enriched in the LF group, and further subgroup analysis revealed enrichment of CD14⁺S100A12⁺ monocytes and depletion of CD14⁺FOS⁺ monocytes in the LF group. Moreover, inflammation scores were significantly different in the Pre, Post and LF groups.

Conclusion

Our study provides a comprehensive cell landscape for patients with MG, identifies two dysregulated monocytes, elucidates the inflammation status and offers a new perspective on understanding the aetiology of functional cure and potential therapeutic strategies for patients with MG.