Extensive and Persistent Extravascular Dermal Fibrin Deposition Characterizes Systemic Sclerosis.

Autor: Browning JL; Department of Microbiology, Boston University Chobanian & Avedesian School of Medicine, Boston, MA.; Department of Rheumatology, Boston University Chobanian & Avedesian School of Medicine, Boston, MA., Bhawan J; Department of Dermatopathology, Boston University Chobanian & Avedesian School of Medicine, Boston, MA.; Department of Pathology and Laboratory Medicine, Boston University Chobanian & Avedesian School of Medicine, Boston, MA., Tseng A; Department of Pathology and Laboratory Medicine, Boston University Chobanian & Avedesian School of Medicine, Boston, MA.; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA., Crossland N; Department of Pathology and Laboratory Medicine, Boston University Chobanian & Avedesian School of Medicine, Boston, MA.; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA., Bujor AM; Department of Rheumatology, Boston University Chobanian & Avedesian School of Medicine, Boston, MA., Akassoglou K; Gladstone Institute of Neurological Disease San Francisco California USA.; Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA., Assassi S; Division of Rheumatology, University of Texas Health Science Center, Houston, TX., Skaug B; Division of Rheumatology, University of Texas Health Science Center, Houston, TX., Ho J; Department of Dermatopathology, Boston University Chobanian & Avedesian School of Medicine, Boston, MA.; Section Dermatology University of the West Indies, Mona Jamaica.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2023 Jan 19. Date of Electronic Publication: 2023 Jan 19.
DOI: 10.1101/2023.01.16.523256
Abstrakt: Systemic sclerosis (SSc) is an autoimmune disease characterized by progressive multiorgan fibrosis. While the cause of SSc remains unknown, a perturbed vasculature is considered a critical early step in the pathogenesis. Using fibrinogen as a marker of vascular leakage, we found extensive extravascular fibrinogen deposition in the dermis of both limited and diffuse systemic sclerosis disease, and it was present in both early and late-stage patients. Based on a timed series of excision wounds, retention on the fibrin deposit of the splice variant domain, fibrinogen α E C, indicated a recent event, while fibrin networks lacking the α E C domain were older. Application of this timing tool to SSc revealed considerable heterogeneity in α E C domain distribution providing unique insight into disease activity. Intriguingly, the fibrinogen-α E C domain also accumulated in macrophages. These observations indicate that systemic sclerosis is characterized by ongoing vascular leakage resulting in extensive interstitial fibrin deposition that is either continually replenished and/or there is impaired fibrin clearance. Unresolved fibrin deposition might then incite chronic tissue remodeling.
Competing Interests: Conflict of Interest: JLB has received consulting fees from Jounce Therapeutics, Mestag, Oncurious and Shattuck Labs as well as lab support from Hoffmann La Roche. KA is the scientific founder, scientific advisor and director of Therini Bio. SA has received grants from Boehringer Ingelheim, Janssen and Momenta to his institution and has received personal consultancy fees from AstraZeneca, CSL Behring, Boehringer Ingelheim and TeneoFour. AMB received honoraria from Biogen.
Databáze: MEDLINE
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