Platelets play an important role in worsening myasthenia gravis (MG), and scientists believe they could become a new treatment target, according to a study published recently in Nature Communications.
This study found that platelets, which are normally thought of as clotting cells, were overactive in patients with untreated MG. They interacted with immune cells in ways that fueled inflammation and were linked with more severe symptoms. Once patients started therapies such as intravenous immunoglobulin or long-term immunosuppressants, platelet activity decreased toward normal.
In untreated MG, researchers found higher platelet counts, abnormal shapes and elevated surface markers of activation. These included CD62P expression and increased levels of soluble CD40 ligand, both indicators of inflammatory activity.
The stronger the platelet changes, the higher the patient’s disease activity score. In contrast, patients who reached minimal clinical status showed platelet features similar to healthy individuals.
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This research also revealed that activated platelets form clusters with white blood cells, particularly neutrophils. These platelet-neutrophil aggregates directly correlated with symptom severity and dropped after treatment.
“Our study reveals morphological alterations in MG platelets, notably a reduction in cell size and heightened microparticle release, which are aligned with the enhanced degranulation activity detected through transcriptome analysis,” explained this study’s authors.
Lab experiments showed that platelets and neutrophils stimulate one another in a harmful cycle: Platelets trigger neutrophils to release damaging structures called NETs, while NETs further activate platelets. This back-and-forth interaction may drive ongoing inflammation in MG.
Beyond neutrophils, platelets also affected T cells, a type of immune cell that shapes long-term immune responses. In laboratory tests, MG platelets promoted T helper 1 cell activity, linked with inflammation, while suppressing regulatory T cells, which normally calm the immune system. The researchers found that a platelet messenger called RANTES played a central role in this effect. Blocking RANTES reduced the harmful T cell responses.
Using advanced RNA sequencing, the team analyzed nearly 89,000 single cells and found that platelets from patients with MG showed dramatic shifts in gene expression. Hundreds of genes tied to inflammation, metabolism and cell communication were altered, creating a signature of immune hyperactivation. These changes were consistent across patients regardless of sex or age.
For patients, this work highlights that MG is not only about nerve-muscle signaling but also about immune cells and platelets interacting in destructive ways. Therapies that calm platelet activity could one day be added to current treatments, possibly making symptoms less severe and relapses less frequent.
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