Platelet activation plays a pro-inflammatory role in myasthenia gravis

Qi Wen, Shu Zhang, Yaye Wang, Haoran Liu, Jingsi Wang, Shengyao Su, Nairong Xie, Yan Lu, Li Di, Min Xu, Min Wang, Hai Chen, Suobin Wang, Wenjia Zhu, Xinmei Wen, Jinming Han, Dongshan Wan, Shufang Zhao, Wanting Lu, Zhen Tao, Jianying Duo, Yue Huang, Guoliang Chai, Ruisheng Duan, Xiaoli Li (), Junwei Hao () and Yuwei Da ()
Additional contact information
Qi Wen: Capital Medical University
Shu Zhang: Capital Medical University
Yaye Wang: Capital Medical University
Haoran Liu: Capital Medical University
Jingsi Wang: Capital Medical University
Shengyao Su: Capital Medical University
Nairong Xie: Capital Medical University
Yan Lu: Capital Medical University
Li Di: Capital Medical University
Min Xu: Capital Medical University
Min Wang: Capital Medical University
Hai Chen: Capital Medical University
Suobin Wang: Capital Medical University
Wenjia Zhu: Capital Medical University
Xinmei Wen: Capital Medical University
Jinming Han: Capital Medical University
Dongshan Wan: Capital Medical University
Shufang Zhao: Capital Medical University
Wanting Lu: Capital Medical University
Zhen Tao: Capital Medical University
Jianying Duo: Capital Medical University
Yue Huang: Capital Medical University
Guoliang Chai: Capital Medical University
Ruisheng Duan: The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital
Xiaoli Li: The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital
Junwei Hao: Capital Medical University
Yuwei Da: Capital Medical University

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Myasthenia gravis (MG) is an autoimmune disorder that disrupts neuromuscular junction function through autoantibodies. Platelets are emerging as key players in the pathogenesis of MG, bridging innate and adaptive immunity. We analyze platelet transcriptome signatures and their interactions with the immune system in AChR+ immunotherapy-naïve MG (nMG) patients using bulk and single-cell RNA sequencing on peripheral blood mononuclear cells (PBMC). nMG patients exhibit upregulation of genes related to activation, inflammation, and cytoskeletal regulation. Increased platelet count, activation, altered morphology, enhanced CD62P expression, and elevated plasma CD40L levels are observed in PBMCs, which diminish with minimal clinical status (MMS). Functionally, platelets show heightened interactions with leukocytes, forming aggregates that correlate with disease severity. These features return to baseline after intravenous immunoglobulin or prolonged immunosuppressive therapy. This study underscores platelet activation’s critical role in MG and supports platelet-targeted therapy.

Date: 2025
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DOI: 10.1038/s41467-025-63750-2

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