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Critical role of neutrophil extracellular traps (NETs) in patients with Behcet’s disease
  1. Alexandre Le Joncour1,2,
  2. Raphael Martos3,
  3. Stephane Loyau3,
  4. Nicolas Lelay3,
  5. Antoine Dossier4,
  6. Aurelie Cazes4,
  7. Pierre Fouret5,
  8. Fanny Domont1,
  9. Thomas Papo4,
  10. Martine Jandrot-Perrus3,
  11. Marie-Christine Bouton3,
  12. Patrice Cacoub1,2,
  13. Nadine Ajzenberg3,6,
  14. David Saadoun1,2,
  15. Yacine Boulaftali3
  1. 1Department of Internal Medicine and Clinical Immunology, Groupe Hospitalier Pitié-Salpêtrière-APHP, Paris, France
  2. 2INSERM UMR_S 959, Immunologie-Immunopathologie-Immunotherapie, i3, Sorbonne Université, Paris, France
  3. 3LVTS, INSERM 1148, Paris, France
  4. 4Department of Internal Medicine, Université Paris Diderot, Sorbonne Paris, Hôpital Bichat- APHP, Paris, Île-de-France, France
  5. 5Department of Anatomopathology, Hôpital de la Pitié-Salpêtrière-APHP, Paris, France
  6. 6Department of Hematology, Université Paris Diderot, Sorbonne Paris, Hôpital Bichat- APHP, Paris, France
  1. Correspondence to Dr Yacine Boulaftali,LVTS, INSERM 1148, Paris, France; yacine.boulaftali{at}


Objectives Behçet’s disease (BD) is a chronic systemic vasculitis. Thrombosis is a frequent and life-threatening complication. The pathogenesis of BD is poorly understood and evidence supporting a role for primed neutrophils in BD-associated thrombotic risk is scant. To respond to inflammatory insults, neutrophils release web-like structures, known as neutrophil extracellular traps (NETs), which are prothrombotic. We evaluated the role of NETs and markers of NETs in BD.

Methods Blood samples were collected from patients with BD, according to the International Study Group Criteria for Behçet's disease, and healthy donors (HD). NET components, including cell-free DNA (CfDNA) and neutrophil enzymes myeloperoxidase (MPO), were assessed in serum or in purified neutrophils from patients with BD and HD.

Results Patients with active BD had elevated serum cfDNA levels and MPO-DNA complexes compared with patients with inactive BD and to HD. In addition, levels of cfDNA and MPO-DNA complexes were significantly higher in patients with BD with vascular involvement compared with those without vascular symptoms. Purified neutrophils from patients with BD exhibited spontaneous NETosis compared with HD. Thrombin generation in BD plasma was significantly increased and positively correlated with the levels of MPO-DNA complexes and cfDNA. Importantly, DNAse treatment significantly decreased thrombin generation in BD plasma but not in HD plasma. In addition, biopsy materials obtained from patients with BD showed NETs production in areas of vasculitic inflammation and thrombosis.

Conclusions Our data show that NETs and markers of NETS levels are elevated in patients with BD and contribute to the procoagulant state. Targeting NETs may represent a potential therapeutic target for the reduction or prevention of BD-associated thrombotic risk.

  • behçet’disease
  • vasculitis
  • neutrophils extracellular traps
  • neutrophils
  • thrombosis

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  • Handling editor Josef S Smolen

  • Contributors ALJ, MJP, M-CB, DS and YB were involved in drafting the article. ALJ, YB and DS had full access to all data in the analysis.Study conception and design: ALJ, DS and YB. Acquisition of data: ALJ, RM, SL, NL, AD, AC, PF, FD, TP, PC, DS and YB. Analysis and interpretation of data: ALJ, RM, SL, NL, AD, AC, MJ-P, M-CB, NA, DS and YB.

  • Funding This work was supported by FDF no 0075823 and DHU FIRE 012 to YB.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The study was approved by the CPP (Comité de Protection des Personnes). The study was done in accordance to the ethical guidelines of the 1975 Declaration of Helsinki.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as online supplementary information.