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

单细胞RNA测序揭示重症肌无力患者的细胞免疫状态和单核细胞失调

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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.

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