Critical role of neutrophil extracellular traps (NETs) in patients with Behcet’s disease
| Autor: | Fanny Domont, Raphael Martos, Pierre Fouret, Nicolas Lelay, Marie-Christine Bouton, Stéphane Loyau, Yacine Boulaftali, Martine Jandrot-Perrus, Patrice Cacoub, Antoine Dossier, David Saadoun, Aurélie Cazes, Thomas Papo, Nadine Ajzenberg, Alexandre Le Joncour |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Neutrophils Immunology Inflammation Behcet's disease Extracellular Traps Severity of Illness Index General Biochemistry Genetics and Molecular Biology Pathogenesis 03 medical and health sciences 0302 clinical medicine Rheumatology Biopsy Humans Immunology and Allergy Medicine 030203 arthritis & rheumatology biology medicine.diagnostic_test business.industry Behcet Syndrome Neutrophil extracellular traps medicine.disease 030104 developmental biology Myeloperoxidase biology.protein Female medicine.symptom business Vasculitis Biomarkers Systemic vasculitis |
| Zdroj: | Annals of the Rheumatic Diseases. 78:1274-1282 |
| ISSN: | 1468-2060 0003-4967 |
| Popis: | ObjectivesBehçet’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.MethodsBlood 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.ResultsPatients 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.ConclusionsOur 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. |
| Databáze: | OpenAIRE |
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