Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Behçet’s disease (BD) is a chronic systemic vasculitis characterised by muco-cutaneous, ocular, gastrointestinal, cerebral recurrent lesions. Venous thrombosis, is a frequent and life-threatening complication. The etiology of BD is poorly understood but activated neutrophils have been proposed to contribute to the disease. However, 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 aim to evaluate the role of NETs in the thrombotic complications in BD disease.
Blood samples were collected from BD patients according to the ACR International Study Group Criteria for Behçet’s disease and healthy controls (HC). Cell free DNA (CfDNA), myeloperoxidase (MPO) and DNA complexes were measured in serum using Picogreen assay and ELISA. NETosis was assessed in purified neutrophils from BD patients and HC, and analyzed by microscopy after immunostaining of MPO and DNA. Thrombin generation assay were performed in plasma of patients and HC.
Active BD patients (n=16) had elevated serum CfDNA levels compared to inactive BD patients (n=23) and to HC (n=8) (2105 ± 249, 1379 ± 79 and 951 ± 64 ng/ml respectively p<0.0001). MPO-DNA complexes were significantly increased in Active BD serum (n=15) compared to inactive BD (n=19) and to HC serum(n=8) (2.84 ± 0.21, 1,92 ± 0.26, and 0.32 ± 0.0,08 OD, respectively, p<0.001). In addition, levels of cfDNA and MPO-DNA complexes were significantly higher in Angio BD serum (n=17) compare to non-angio BD serum(n=22) (2073 ± 237 vs 1390± 0.83 ng/ml p=0.008 and 2,96 ± 0.13 vs 1.80 ± 0.26 OD p=0.004, respectively). Purified neutrophils from BD patients exhibited spontaneous NETosis compared to HC (31.7 ± 4.4% vs 5.4 ± 1.9% respectively, p=0.004). Consistently, PMA-activated neutrophils from BD patients have increased NET formation compared to neutrophils from HC (41.8 ± 2.7% vs 18 ± 3.8% respectively, p=0.002). Thrombin generation in BD plasma was significantly increased and positively correlated with MPO-DNA complexes (r2= 0.84, p=0.001 and cfDNA (r2= 0.9, p=0.002). Importantly, DNAse treatment significantly decreased thrombin generation in BD plasma but had no effect in HC plasma suggesting a procoagulant role of NETs.
Our data show for the first time the critical role of circulating NETs in BD patients. NETs may be involved in thrombi formation. Targeting NETs may represent a potential therapeutic option in BD.
To cite this abstract in AMA style:LE JONCOUR A, Loyau S, Lelay N, Bouton MC, Dossier A, Desbois AC, Domont F, Papo T, Jandrot-Perrus M, Cacoub P, Ajzenberg N, saadoun D, Boulaftali Y. Critical Role of Neutrophil Extracellular Traps (NETs) in Patients with Behcet’s Disease [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/critical-role-of-neutrophil-extracellular-traps-nets-in-patients-with-behcets-disease/. Accessed November 12, 2019.
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