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Research Article: Tissue factor-associated neutrophil extracellular traps in dermatomyositis: procoagulant activity and endothelial activation in vitro

Date Published: 2026-10-30

Abstract:
Dermatomyositis (DM) is an immune-mediated myopathy characterized by inflammatory and vascular manifestations and variable systemic involvement; however, the interplay among neutrophil activation, complement, and coagulation remains unclear. We investigated whether serum from patients with DM induces tissue factor (TF)-associated neutrophil extracellular traps (NETs) and examined their functional effects in vitro . Serum from seven patients with active DM and seven matched healthy individuals was analyzed for inflammatory mediators, citrullinated histone H3 (CitH3), thrombin–antithrombin (TAT) complexes, soluble C5b-9, and DNase-I activity. Control neutrophils were exposed to DM serum and, then, NET formation, TF expression and activity, and thrombin generation were assessed. Inhibition experiments targeting complement, TF, and NETs were performed. Co-culture experiments assessed endothelial activation, while skin biopsies were examined by immunofluorescence. Patients with DM exhibited increased inflammatory mediators, CitH3, TAT complexes, and soluble C5b-9, together with reduced DNase-I activity. DM serum induced TF expression and release of TF-associated NETs by control neutrophils. DNase-I and eculizumab reduced NET formation, while eculizumab additionally decreased TF mRNA expression and NET-associated TF activity. TF-associated NETs promoted adhesion molecule expression by human aortic endothelial cells, an effect attenuated by DNase-I or TF neutralization. TF-positive NET fragments were detected in lesional DM skin but not healthy skin. These exploratory findings support a contribution of C5-dependent complement activation to TF-associated NET formation and show that these NETs can enhance thrombin generation and endothelial activation in vitro . Their relationship to clinical vasculopathy or thrombotic risk remains unknown, providing evidence for potential links between inflammation, thrombosis, and vascular injury in DM.

Introduction:
Dermatomyositis (DM) is an immune-mediated myopathy characterized by inflammatory and vascular manifestations and variable systemic involvement; however, the interplay among neutrophil activation, complement, and coagulation remains unclear. We investigated whether serum from patients with DM induces tissue factor (TF)-associated neutrophil extracellular traps (NETs) and examined their functional effects in vitro .

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