Systemic sclerosis is a multisystem autoimmune disease characterized by vascular dysfunction, immune dysregulation, and progressive tissue fibrosis. Cardiopulmonary complications and peripheral vascular involvement are the principal causes of disability and mortality.
Extracellular vesicles (EVs) have emerged as key mediators of paracrine intercellular communication. Preclinical studies further suggest that EVs mediate long-range inter-organ communication through the circulation. However, the inability to directly track EV trafficking in vivo in humans has limited the understanding of their contribution to systemic inter-organ communication.
The investigators propose that systemic sclerosis provides a unique human model for investigating circulating EV-mediated inter-organ communication in a multisystem disease. The central hypothesis is that arteriovenous differences in the molecular and cellular characteristics of circulating EVs reflect their dynamic exchange between individual organs and the bloodstream, and that these differences are associated with disease severity. Comparison of EVs across the circulation, rather than relying exclusively on peripheral blood samples, enables a more direct assessment of organ-specific EV release and uptake.
Characterizing EV dynamics along the circulatory pathway has the potential to identify novel biomarkers and therapeutic targets for systemic sclerosis while providing fundamental insights into EV-mediated inter-organ communication in humans.
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Single group
Blood sampling, nailfold capillaroscopy
Diagnostic testBlood collection during right heart catheterization
Transcardiopulmonary extracellular vesicle gradient
Arteriovenous differences between the pulmonary artery and the ascending aorta in extracellular vesicle characteristics, including particle concentration, size distribution, protein expression profile, and RNA expression profile. Treatment failure in patients with pulmonary arterial hypertension at 24 weeks, defined as the occurrence of at least one of the following events: an improvement of less than 30 meters in the 6-minute walk distance (6MWD); a reduction in NT-proBNP of less than 30% in patients with baseline levels \>300 pg/mL; worsening of World Health Organization (WHO) functional class; or death due to complications of pulmonary arterial hypertension. Treatment failure in patients with recurrent digital ulcers, defined as the development of new digital ulcers or gangrene at sites previously affected by digital ulcers.
Peripheral extracellular vesicle gradient
Arteriovenous differences between the cephalic vein and the radial artery in extracellular vesicle characteristics, including particle concentration, size distribution, protein expression profile, and RNA expression profile.
Treatment failure in participants with pulmonary arterial hypertension.
Treatment failure, defined as the occurrence of at least one of the following: improvement in 6-minute walk distance of less than 30 meters; reduction in NT-proBNP of less than 30% in participants with baseline NT-proBNP \>300 pg/mL; worsening of World Health Organization functional class; or death related to pulmonary arterial hypertension.
Treatment failure in participants with recurrent digital ulcers.
Development of new digital ulcers or gangrene at sites previously affected by digital ulcers.
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