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Neutrophil-mediated mechanisms in non-vascular Behçet’s syndrome
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  • Alessandra Bettiol,
  • MATTEO BECATTI,
  • Elena Slvestri,
  • Flavia Rita Argento,
  • Eleonora Fini,
  • Amanda Mannucci,
  • Silvia Galora,
  • Irene Mattioli,
  • Maria Letizia Urban,
  • Danilo Malandrino,
  • Adalgisa Palermo,
  • Niccolò Taddei,
  • Giacomo Emmi,
  • Domenico Prisco,
  • Claudia Fiorillo
Alessandra Bettiol
University of Firenze
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MATTEO BECATTI
University of Florence
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Elena Slvestri
University of Firenze
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Flavia Rita Argento
University of Florence
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Eleonora Fini
University of Florence
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Amanda Mannucci
University of Florence
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Silvia Galora
University of Florence
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Irene Mattioli
University of Florence
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Maria Letizia Urban
University of Florence
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Danilo Malandrino
University of Florence
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Adalgisa Palermo
University of Florence
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Niccolò Taddei
University of Firenze
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Giacomo Emmi
University of Florence
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Domenico Prisco
University of Florence, Italy
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Claudia Fiorillo
University of Firenze
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Abstract

Objective: Behçet’s syndrome (BS) is a systemic vasculitis with several clinical manifestations. Neutrophils hyperactivation mediates vascular BS involvement, via a massive production of reactive oxygen species (ROS) and the release of neutrophil extracellular traps (NETs). We investigated neutrophil-mediated mechanisms of damage in non-vascular BS manifestations and explored in vitro the effects of colchicine in counteracting these mechanisms. Methods: NETs and intracellular ROS production was assessed in blood samples from 80 BS patients (46 with active non-vascular BS, 34 with inactive disease) and 80 healthy controls. Moreover, isolated neutrophils were incubated for 1 hour with an oxidating agent (2,2′-azobis (2-amidinopropane) dihydrochloride; 250nM), and the ability of pure colchicine pre-treatment (100ng/ml) to counteract oxidation-induced damage was assessed. Results: Patients with active non-vascular BS had remarkably increased NET levels [21.2 (IQR 18.3-25.9) mU/ml] compared to patients with inactive disease [16.8 (13.3-20.2) mU/ml] and to controls [7.1 (5.1-8.7) mU/ml], p<0.001]. Also, intracellular ROS tended to be increased in active BS, although not significantly. In active non-vascular BS, NETs correlated with neutrophils ROS production (p<0.001) and were particularly increased in patients with active mucosal (p<0.001), articular (p=0.004), and gastrointestinal symptoms (p=0.006). On isolated neutrophils, colchicine significantly reduced oxidation-induced NET production and cell apoptosis, though not via an antioxidant activity. Conclusion: Neutrophil-mediated mechanisms might be directly involved in non-vascular BS, and NETs, more than ROS, might drive the pathogenesis of mucosal, articular and intestinal manifestations. Colchicine might be effective to counteract neutrophils-mediated damage in BS, although further studies are needed.

Peer review status:IN REVISION

30 Jul 2021Submitted to Clinical & Experimental Immunology
02 Aug 2021Assigned to Editor
02 Aug 2021Submission Checks Completed
03 Aug 2021Reviewer(s) Assigned
24 Aug 2021Review(s) Completed, Editorial Evaluation Pending
25 Aug 2021Editorial Decision: Revise Minor