Critical Role of Neutrophil Extracellular Traps (NETs) in Patients with Behcet’s Disease

Alexandre LE JONCOUR^1,2, Stephane Loyau³, Nicolas Lelay⁴, Marie-Christine Bouton⁵, Antoine Dossier⁶, Anne-Claire Desbois⁷, Fanny Domont⁸, Thomas Papo⁹, Martine Jandrot-Perrus⁵, Patrice Cacoub¹⁰, Nadine Ajzenberg⁵, David saadoun⁷ and Yacine Boulaftali², ¹Département Hospitalo-Universitaire Inflammation-Immunopathologie-Biotherapie (DHU i2B), F-75005, Paris, France., National center for Autoimmune and Systemic rare diseases and for Autoinflammatory diseases, Paris, France, ²INSERM 1148, CHU Xavier Bichat, paris, France, ³Unité INSERM 1148, CHU Xavier Bichat, Faris, France, ⁴2. Unité INSERM 1148, CHU Xavier Bichat, paris, France, ⁵Unité INSERM 1148, CHU Xavier Bichat, paris, France, ⁶3. Service de Médecine Interne, CHU Xavier Bichat, paris, France, ⁷Département Hospitalo-Universitaire Inflammation-Immunopathologie-Biotherapie, National center for Autoimmune and Systemic rare diseases and for Autoinflammatory diseases, Paris, France, ⁸Département Hospitalo-Universitaire Inflammation-Immunopathologie-Biotherapie, National center for Autoimmune and Systemic rare diseases and for Autoinflammatory diseases, paris, France, ⁹Service de Médecine Interne, CHU Xavier Bichat, Paris, France, ¹⁰Département de Médecine Interne et Immunologie Clinique, National center for Autoimmune and Systemic rare diseases and for Autoinflammatory diseases, Paris, France

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Behcet's syndrome, Neutrophil Extracellular Traps, neutrophils, thrombosis and vasculitis

Session Information

Date: Tuesday, November 7, 2017

Session Title: Innate Immunity and Rheumatic Disease

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose:

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.

Methods:

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.

Results:

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.

Conclusion:

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.

Disclosure: A. LE JONCOUR, None; S. Loyau, None; N. Lelay, None; M. C. Bouton, None; A. Dossier, None; A. C. Desbois, None; F. Domont, None; T. Papo, None; M. Jandrot-Perrus, None; P. Cacoub, None; N. Ajzenberg, None; D. saadoun, None; Y. Boulaftali, None.

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 January 19, 2020.

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