Mitochondrial-Mediated Platelet Activation in Polymyalgia Rheumatica.

Area of Science:

• Immunology
• Rheumatology
• Cell Biology

Background:

• Platelet activation is implicated in polymyalgia rheumatica (PMR) pathogenesis.
• Extracellular mitochondria are released upon platelet activation, but their role in PMR is unknown.

Purpose of the Study:

• To investigate the presence of extracellular mitochondria and their role in platelet activation in PMR patients.
• To assess autoantibodies against mitochondrial antigens in PMR patients.

Main Methods:

• Measured plasma levels of platelet activation marker TSP-1, mitochondrial peptide fMET, and anti-MFN1 autoantibodies in PMR patients and healthy controls (HCs).
• Assessed platelet activation induced by patient-derived mitochondria using flow cytometry.
• Evaluated changes before and after glucocorticoid therapy.

Main Results:

• Elevated anti-MFN1 IgG, fMET, and TSP-1 levels were found in PMR patients compared to HCs.
• These markers decreased after glucocorticoid therapy, particularly in PMR without GCA.
• Mitochondria opsonized with PMR patient plasma induced significantly higher platelet activation in HC platelets.

Conclusions:

• PMR patients exhibit increased platelet activation and circulating mitochondrial antigens/antibodies.
• Blocking mitochondrial-mediated platelet activation could be a therapeutic strategy for PMR.