Tissue factor-associated neutrophil extracellular traps in dermatomyositis: procoagulant activity and endothelial activation in vitro
Abstract
IntroductionDermatomyositis (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.MethodsSerum 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.ResultsPatients 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.DiscussionThese 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.
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BibTeX
@article{ntinopoulou2026tissue,
title = {{Tissue factor-associated neutrophil extracellular traps in dermatomyositis: procoagulant activity and endothelial activation in vitro}},
author = {Maria Ntinopoulou and Lamprini Efstathiou and Aliki I. Venetsanopoulou and Pavlos Simonopoulos and Evangeli Lampri and Nikolaos Koletsos and Nikolaos Zintziovas and Antigoni Sourla and Paraskevi V. Voulgari and Akrivi Chrysanthopoulou},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1926259},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1926259},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Tissue factor-associated neutrophil extracellular traps in dermatomyositis: procoagulant activity and endothelial activation in vitro
AU - Maria Ntinopoulou
AU - Lamprini Efstathiou
AU - Aliki I. Venetsanopoulou
AU - Pavlos Simonopoulos
AU - Evangeli Lampri
AU - Nikolaos Koletsos
AU - Nikolaos Zintziovas
AU - Antigoni Sourla
AU - Paraskevi V. Voulgari
AU - Akrivi Chrysanthopoulou
PY - 2026
DA - 2026/10/30
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1926259
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1926259
AB - IntroductionDermatomyositis (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.MethodsSerum 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.ResultsPatients 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.DiscussionThese 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.
SN - 1664-3224
ER -