Platelet activation plays a pro-inflammatory role in myasthenia gravis
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.
Authors
- Shufang Zhao
- Rui‐Sheng Duan (ORCID: https://orcid.org/0000-0002-7481-7641)
- Jianying Duo
- Wenjia Zhu (ORCID: https://orcid.org/0000-0003-1397-4544)
- Yaye Wang (ORCID: https://orcid.org/0000-0003-0505-3243)
- Junwei Hao (ORCID: https://orcid.org/0000-0002-3075-5434)
- Shengyao Su (ORCID: https://orcid.org/0000-0002-5020-7056)
- Nairong Xie (ORCID: https://orcid.org/0009-0008-4616-2861)
- Yuwei Da
- Dongshan Wan
- Haoran Liu (ORCID: https://orcid.org/0000-0001-8216-3679)
- Guoliang Chai (ORCID: https://orcid.org/0000-0001-9658-6381)
- Xinmei Wen
- Suobin Wang
- Y. Huang (ORCID: https://orcid.org/0000-0002-3515-9500)
- Xiaoli Li (ORCID: https://orcid.org/0000-0001-9245-0647)
- Shu Zhang (ORCID: https://orcid.org/0000-0003-0928-6503)
- Di Li (ORCID: https://orcid.org/0000-0003-0262-6827)
- Min Xu (ORCID: https://orcid.org/0009-0003-5839-0259)
- Hai Chen (ORCID: https://orcid.org/0000-0003-1605-8082)
- Lu Yan (ORCID: https://orcid.org/0009-0009-6050-4909)
- Zhen Tao (ORCID: https://orcid.org/0000-0003-0071-5172)
- Jingsi Wang (ORCID: https://orcid.org/0000-0003-0701-8425)
- Jinming Han
- Q. G. Wen (ORCID: https://orcid.org/0000-0002-5556-9419)
- Wanting Lu
- Min Wang (ORCID: https://orcid.org/0009-0009-9732-3570)
Institutions
- Shanxi Medical University (CN)
- Capital Medical University (CN)
- First Hospital of Shanxi Medical University (CN)
- Shandong Provincial QianFoShan Hospital (CN)
- Shandong First Medical University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-10-02
- DOI
- https://doi.org/10.1038/s41467-025-63750-2
- Citations
- 4
- Primary Topic
- Myasthenia Gravis and Thymoma
- Type
- article
- Field-Weighted Citation Impact
- 5.56
Funders
- National Natural Science Foundation of China
- Beijing Jiaotong University