scholarly journals Saliva and Serum Cytokine Profiles During Oral Ulceration in Behçet’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Tanya Novak ◽  
Mojgan Hamedi ◽  
Lesley Ann Bergmeier ◽  
Farida Fortune ◽  
Eleni Hagi-Pavli
Keyword(s):  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Serum Cytokine ◽  
Oral Ulceration ◽  
Behcet's Disease ◽  
Cytokine Profiles ◽  
Oral Ulcers ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Ifn Γ

Behçet’s disease (BD) is a chronic, multi-systemic disorder of unknown aetiology typified by recurrent oral and genital mucocutaneous lesions, uveitis and vasculitis. Innate and adaptive immune system dysregulation has been implicated in pathogenesis with alterations in serum cytokine profiles. Few studies have investigated salivary cytokines in BD, despite more than 90% of BD patients first presenting with oral ulceration. The aim of this pilot study was twofold; firstly to investigate whether cytokine levels in matched serum and saliva samples show a differential profile in BD (with and without oral ulcers), recurrent aphthous stomatitis (RAS) and healthy controls (HCs), and secondly, to explore if any differential profiles in serum and/or saliva could provide a panel of cytokines with diagnostic and therapeutic potential for BD. Concentrations of 12 cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IFN-γ, TNF-α, TNF-β) were measured using the Human Th1/Th2 11-Plex FlowCytomix™ kit with IL-17A, in BD (N=20), RAS (N=6) and HCs (N=10). A differential range of cytokines was detected in serum and saliva with the majority of cytokine levels higher in saliva. The most prevalent salivary cytokines were IL-1β, IL-2, IL-8, IL-10 and TNF-α present in all samples in contrast to serum where the most prevalent cytokine detected was IL-8 (91.9%). The least abundant cytokine was IFN-γ in both saliva (43.2%) and serum (2.7%). After normalizing saliva for protein content, BD patients with oral ulcers (BD-MA) had significantly higher levels of salivary IL-1β (p=0.01), IL-8 (p=0.02), TNF-α (p=0.004) and IL-6 (p=0.01) than HCs. Notably, BD patients without oral ulcers (BD-MQ) also had significantly higher salivary IL-1β, IL-8 and TNF-α (p ≤ 0.05) than HCs. During relapsed (BD-RE) and quiet (BD-Q) systemic episodes, salivary IL-β and TNF-α were also significantly increased with IL-8 significantly higher only in BD-Q (p=0.02). BD oral ulcers signify a potential reactivation of systemic inflammation. Identifying cytokines released during asymptomatic episodes and oral ulceration might lead to targeted drug therapy to prevent recurrent oral ulcers and possible disease relapse. This is the first study to report salivary cytokine levels in BD. The detectable levels suggests cytokine profiling of BD saliva may provide an alternative, less invasive, sensitive procedure for frequent monitoring of disease activity and progression.

scholarly journals Neutrophil Extracellular Traps Promote Aberrant Macrophages Activation in Behçet’s Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Lu Li ◽  
Xin Yu ◽  
Jinjing Liu ◽  
Zhimian Wang ◽  
Chaoran Li ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Neutrophil Extracellular Traps ◽  
Histone H4 ◽  
Behcet's Disease ◽  
Extracellular Traps ◽  
Tnf Α ◽  
Ifn Γ

Neutrophil extracellular traps (NETs) are upregulated and promote thrombosis in Behçet’s disease (BD). However, whether NETs promote autoinflammation in BD remains unclear. This study aimed to investigate the potential role of NETs in promoting macrophage activation in BD. Firstly, we quantified NETs by measuring double-stranded DNA (dsDNA) using PicoGreen and calculating the proportion of NETosis. Then macrophages were stimulated with BD- or healthy controls (HC)-derived NETs, and IL-8 and TNF-α production and IFN-γ+ CD4+ T cells differentiation were measured using ELISA and flow cytometry, respectively. The protein components in NETs were analyzed by western blot. Macrophages were stimulated with Histone H4 neutralized NETs, and IL-8 and TNF-α production were measured using ELISA. The level of 8-hydroxydeoxyguanosine (8-OHdG) DNA in NETs was measured using ELISA. The levels of reactive oxygen species (ROS) in serum and neutrophils were measured using ROS probes by a microplate reader and flow cytometry. We found that circulating NETs and neutrophil-derived NETs were significantly higher in BD than HC. BD NETs stimulated macrophages produced higher levels of IL-8 and TNF-α, and promoted IFN-γ+ CD4+ T cells differentiation. BD NETs were enriched in Histone H4, and neutralizing Histone H4 abrogated the BD NETs-mediated IL-8 production by macrophages, but not TNF-α. Also, BD neutrophils produced more 8-OHdG DNA than HC neutrophils, and the percentage of 8-OHdG DNA in dsDNA from BD neutrophils was also higher than that of HC neutrophils. The ROS levels in serum and neutrophils were both higher in BD than HC. Our findings suggested that excessive BD NETs promoted macrophages activation and facilitated IFN-γ+ CD4+ T cells differentiation. Higher levels of Histone H4 and oxidized DNA in BD NETs might mediate macrophages hyperactivation.

scholarly journals Serum Cytokine Levels in Behçet's Disease

2014 ◽  
Vol 29 (4) ◽  
pp. 317-320 ◽  
Author(s):  
Zeynep Meltem Akkurt ◽  
Mehtap Bozkurt ◽  
Derya Uçmak ◽  
Hatice Yüksel ◽  
Haydar Uçak ◽  
...  
Keyword(s):  
Behçet’S Disease ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Serum Cytokine ◽  
Behcet's Disease ◽  
Cytokine Levels

Serum cytokine profiles in Behçet's disease: Is there a role for IL-15 in pathogenesis?

2008 ◽  
Vol 121 (1) ◽  
pp. 7-12 ◽  
Author(s):  
S.J. Curnow ◽  
K. Pryce ◽  
N. Modi ◽  
B. Knight ◽  
E.M. Graham ◽  
...  
Keyword(s):  
Behçet’S Disease ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Serum Cytokine ◽  
Behcet's Disease ◽  
Cytokine Profiles

scholarly journals AB0531 GOLIMUMAB IN THE TREATMENT OF SEVERE AND/OR REFRACTORY VASCULO-BEHÇET’S DISEASE: A SINGLE-CENTRE EXPERIENCE IN CHINA

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1562.1-1563
Author(s):  
L. Sun ◽  
J. Liu ◽  
W. Zheng
Keyword(s):  
Aortic Regurgitation ◽  
Behçet’S Disease ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
High Dose ◽  
Efficacy And Safety ◽  
Behcet's Disease ◽  
Severe Aortic Regurgitation ◽  
Tnf Α

Background:Vascular involvement is one of the leading causes of mortality and morbidity in Behcet’s Disease (BD)1. Surgical treatments are difficult for Vaculo-BD (VBD) patients due to the high risk of serious postoperative complications without effective and promptly perioperative immunotherapy2, 3. Anti-tumor necrosis factor alpha (TNF-α) therapy has been reported as a potential treatment in severe VBD, e.g. infliximab (IFX) and adalimumab (ADA). However, only few case reports are available regarding the fully humanized monoclonal antibody to TNF-α, golimumab (GOL), in the management of VBD4.Objectives:The objective of this study was to report the efficacy and safety of GOL for the treatment of severe and/or refractory VBD.Methods:We retrospectively analyzed the efficacy and safety profile of patients with severe and/or refractory VBD treated with GOL in our medical center between 2018 to 2020.Results:Nine VBD patients (8 male and 1 female) were enrolled, with a mean age and median course of 37±8.6 years and 72 months (range 12 to 300), respectively. Cardiac involvements (severe aortic regurgitation secondary to BD) were presented in 7 patients, including 2 patients with post-operative paravalvular leakage (PVL) after aortic valve replacement surgery. Multiple vascular lesions were documented in the other 2 patients, including one patient with life-threatening multiple pulmonary aneurysms, pulmonary thromboembolism and recurrent deep vein thrombosis, and another patient with abdominal aortic pseudoaneurysm and multiple artery stenosis and occlusion. Prior to GOL therapy, all patients experienced disease progression despite high-dose glucocorticoids combined with multiple immunosuppressants. Moreover, seven patients required effective and fast control of inflammation and a decrease of glucocorticoid dose during the perioperative period. They were treated with GOL, 50mg every 4 weeks, in combination with background low-or medium-dose glucocorticoids and immunosuppressants, for a median of 6 (range 3-15) months. After a mean duration of follow-up of 10 (range 2-6) months, all patients achieved improvement both in clinical symptoms and serum inflammation markers. The ESR level [4.88±4.94 mm/h vs 31.13±31.78mm/h, P<0.01] and CRP level [1.9 (0.11-3.73)mg/L vs 24.3 (0.4-85.57)mg/L, P<0.01] significantly decreased. The dosage of glucocorticoid[10 (0-15) vs 40 (0-100)mg/d, P<0.01] effectively tapered, indicating a potential steroid-sparing effect. No newly-onset aneurysm and recurrent venous thrombosis were observed. Also, one patient had a marked reduction in size and number of pulmonary aneurysms. No post-operative PVL was observed in the five patients after Bentall operation with a median follow-up of 10 months. One patient with severe aortic regurgitation remained stable and without surgical intervention with the treatment of GOL for 16 months. No severe complication occurred in one patient after underwent endovascular repair of abdominal aorta for 8 months. GOL was well-tolerated, and no serious adverse event was observed.Conclusion:Our results suggested that GOL is safe and effective for the treatment of patients with severe and / or refractory VBD. Further controlled studies are warranted to confirm the therapeutic potential of GOL in VBD patients.Disclosure of Interests:None declared

TNF-α gene polymorphisms in Iranian Azeri Turkish patients with Behcet’s Disease

2009 ◽  
Vol 30 (2) ◽  
pp. 285-289 ◽  
Author(s):  
Mortaza Bonyadi ◽  
Zohreh Jahanafrooz ◽  
Mohsen Esmaeili ◽  
Susan Kolahi ◽  
Alireza Khabazi ◽  
...  
Keyword(s):  
Behçet’S Disease ◽  
Gene Polymorphisms ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Behcet's Disease ◽  
Tnf Α ◽  
Turkish Patients

Determination of mir-155 and mir-146a expression rates and its association with expression level of TNF-α and CTLA4 genes in patients with Behcet’s disease

2018 ◽  
Vol 204 ◽  
pp. 55-59 ◽  
Author(s):  
Sousan Kolahi ◽  
Mohammad-Jahed Farajzadeh ◽  
Shahriar Alipour ◽  
Alireza Abhari ◽  
Jafar Farhadi ◽  
...  
Keyword(s):  
Behçet’S Disease ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Expression Level ◽  
Behcet's Disease ◽  
Tnf Α

scholarly journals Comparative effectiveness of various immunosuppressive therapy regimens for uveitis in patients with Behçet’s disease

2021 ◽  
Vol 59 (2) ◽  
pp. 173-183
Author(s):  
T. A. Lisitsyna ◽  
G. A. Davydova ◽  
Z. S. Alekberova ◽  
R. G. Goloeva ◽  
L. A. Katargina ◽  
...  
Keyword(s):  
Immunosuppressive Therapy ◽  
Behçet’S Disease ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Total Activity ◽  
Pulse Therapy ◽  
Intraocular Inflammation ◽  
Behcet's Disease ◽  
Tnf Α ◽  
Before And After

The aim – to evaluate the effectiveness of various immunosuppressive therapy schemes for current uveitis used in real clinical practice in patients with Behçet’s disease (BD).Material and methods. The study included 531 patients with a reliable (ICBD criteria 2014) diagnosis of BD, observed in the V.A. Nasonova Research Institute of Rheumatology from 2006 to 2020. The majority were men (331 (62.3%)). The average age (M±SD) was 32.9±10.0 years, the median duration of BD (Me (25%; 75%)) – 96 (48; 174) months. 60.4% patients had uveitis, 70.7% – exacerbation of uveitis (EU). Uveitis activity was assessed by the BOS24 index (Behçet’s disease Ocular attack Score 24) in 202 patients with EU. The total activity of BD was evaluated according to BDCAF index (Behçet’s Disease Current Activity Form). Glucocorticoids (GC) was systematically received by 68.7% patients with EU, including 51.5% in the form of pulse therapy. 88.9% patients with EU received cytotoxics: 33.5% – cyclosporine (CS), 20.7% – azathioprine (AZA), 11.4% – AZA+COL, 8.8% – AZA+CS, 7.5% – colchicine (COL), 3.9% – cyclophosphamide (CPh). 11.9% patients with EU were prescribe Biologics, mainly i-TNF-α (11,4%: 8,8% – adalimumab, 2.2% – infliximab, 0.4% – golimumab) and rituximab (0.4%). The effectiveness of therapy was evaluated on average after 18.0 (8.0; 36.0) months.Results. According to the dynamics of BDCAF, by the end of follow-up, BD activity significantly decreased in all groups, with the exception of patients who received COL. A more significant decrease in BDCAF was observed in the combination therapy groups: AZA+CS (ΔBDCAF=–4.08±3.60), AZA+COL (ΔBDCAF=–3.57±2.50), as well as in the CS group (ΔBDCAF=–3.57±3.39), but no statistically significant differences in ΔBDCAF between the groups were obtained, which does not allow us to speak about a significant advantage of a particular drug. There were no significant differences in ΔBDCAF between patients who received (ΔBDCAF=–3.41±3.89) and those who did not receive (ΔBDCAF=–3.59±3.23) Biologics. According to the dynamics of BOS24, the most effective for relieving symptoms of intraocular inflammation were CS (ΔBOS24=–7.0 (–12.0; –3.0)), AZA (ΔBOS24=–7.0 (–15.0; –2.0)), a combination of CS+AZA (ΔBOS24=–5.0 (–8.0; –2.0)) and CPh (ΔBOS24=–4.0 (–14.0; –2.0). The differences between BOS24 before and after treatment in these groups were statistically significant. When assigning AZA+COL (ΔBOS24=–1.0 (–4.0; 0)) or COL (ΔBOS24=–0.5 (–2.0; 0)) uveitis activity decreased during therapy, but not significantly. According to ΔBOS24, uveitis therapy by CS was statistically significantly more effective compared to AZA+COL and COL; and AZA treatment, compared to COL. Biologics, mainly adalimumab, significantly and rapidly reduce the severity of intraocular inflammation (ΔBOS24=–7.0 (–18.0; 0)) compared with GC and cytotoxics (ΔBOS24=–4,0 (–9,0; –1,0)), however statistically significant differences between the groups were not obtained due to the small number of Biologics groups.Conclusion. CS, AZA and their combination, as well as i-TNF-α (mainly adalimumab) are more effective for relieving uveitis symptoms in patients with BD. BOS24 is a reliable tool for quantifying the activity of uveitis in BD patients and its dynamics against the background of anti-inflammatory and immunosuppressive therapy.

P 085 Prognosis of recurrent oral ulceration in Behçet's disease

1993 ◽  
Vol 14 ◽  
pp. 96s
Author(s):  
Eun So Lee ◽  
Won Hur ◽  
Dongsik Bang ◽  
Seung Hun Lee ◽  
Sungnack Lee ◽  
...  
Keyword(s):  
Behçet’S Disease ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Oral Ulceration ◽  
Behcet's Disease
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