Extensive and Persistent Extravascular Dermal Fibrin Deposition Characterizes Systemic Sclerosis

Area of Science:

• Immunology
• Vascular Biology
• Dermatology

Background:

• Systemic sclerosis (SSc) is an autoimmune disease causing progressive fibrosis.
• Perturbed vasculature is a key early factor in SSc pathogenesis.
• Fibrinogen deposition in tissue indicates vascular leakage.

Approach:

• Used fibrinogen as a marker for vascular leakage in SSc patients.
• Developed a fibrinogen α_EC domain timing tool to assess fibrin deposition age.
• Examined fibrinogen deposition in dermal tissue across SSc subtypes and disease stages.

Key Points:

• Extensive extravascular fibrinogen deposition was observed in the dermis of both limited and diffuse SSc patients.
• The fibrinogen α_EC domain indicated recent vascular leakage events.
• Fibrinogen α_EC domain accumulation was also noted in macrophages.
• Heterogeneous α_EC domain distribution revealed insights into SSc disease activity.

Conclusions:

• SSc is characterized by continuous vascular leakage and interstitial fibrin deposition.
• Impaired fibrin clearance or continuous replenishment contributes to fibrin accumulation.
• Unresolved fibrin deposition may drive chronic tissue remodeling in SSc.