Systemic sclerosis & Raynaud's
A Cooperative Release of Mitochondrial DNA From Platelets and Neutrophils Drives an Interferon Signature in Systemic Sclerosis
Authors' conclusion
SSc plasma is characterized by highly abundant mtDNA, which drives feedback loops amplifying its own release from both neutrophils and platelets.
Study context
- Population
- Patients with systemic sclerosis (SSc) and healthy controls; plasma, neutrophils and platelets
- Comparison
- Patients with SSc vs healthy controls
Main finding
As reported in the abstract
- Median plasma Mitochondrial DNA (mtDNA) levels 152-fold higher in SSc vs healthy controls (HCs); nuclear DNA levels similar
- mtDNA from SSc plasma highly oxidized
- SSc-derived mtDNA promoted its own release by NETosis (most potently in SSc neutrophils) and by platelet activation
- Oxidized mtDNA from SSc platelets in complex with CXCL4 further stimulated mtDNA release in neutrophils and platelets
- Plasma mtDNA correlated with type I interferon (IFN) concentrations in SSc; SSc blood showed elevated IFN-stimulated gene expression
- SSc plasma mtDNA induced IFN signaling and neutrophil extracellular trap (NET) formation via endosomal Toll-like receptors, cGAS/STING and the JAK/STAT pathway
- IFN receptor and JAK inhibition antagonized the proNETotic effects of IFN
Original publication
A Cooperative Release of Mitochondrial DNA From Platelets and Neutrophils Drives an Interferon Signature in Systemic Sclerosis. Arthritis Rheumatol. Published 16 March 2026. doi:10.
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