scholarly journals Case Report: A Case of Intestinal Behçet's Disease Exhibiting Enhanced Expression of IL-6 and Forkhead Box P3 mRNA After Treatment With Infliximab

2021 ◽  
Vol 8 ◽  
Author(s):  
Keisuke Yoshikawa ◽  
Tomohiro Watanabe ◽  
Ikue Sekai ◽  
Ryutaro Takada ◽  
Akane Hara ◽  
...  

Behçet's disease (BD) is a rare inflammatory condition characterized by oral and genital ulcers, skin lesions, as well as ophthalmological, neurological, and gastrointestinal manifestations. BD involving the gastrointestinal tract is known as intestinal BD. The mucosa of the gastrointestinal tract of patients with intestinal BD exhibits enhanced levels of proinflammatory cytokines, such as IL-1β, IL-6, and TNF-α. These proinflammatory cytokines play pathogenic roles in the development of BD, as evidenced by the fact that biologics targeting these cytokines effectively induce BD remission. It should be noted, however, that the molecular mechanisms by which the blockade of these cytokines suppresses chronic inflammatory responses in BD are poorly understood. Herein, we report a case of intestinal BD resistant to prednisolone that was successfully treated with infliximab (IFX). The induction of remission by IFX was accompanied by a marked elevation of IL-6 and forkhead box P3 (FOXP3) at mRNA level. This case suggests that induction of remission by IFX is mediated not only by the suppression of TNF-α-mediated signaling pathways, but also by the promotion of IL-6 expression and accumulation of regulatory T cells expressing FOXP3.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1562.1-1563
Author(s):  
L. Sun ◽  
J. Liu ◽  
W. Zheng

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


2009 ◽  
Vol 30 (2) ◽  
pp. 285-289 ◽  
Author(s):  
Mortaza Bonyadi ◽  
Zohreh Jahanafrooz ◽  
Mohsen Esmaeili ◽  
Susan Kolahi ◽  
Alireza Khabazi ◽  
...  

2018 ◽  
Vol 204 ◽  
pp. 55-59 ◽  
Author(s):  
Sousan Kolahi ◽  
Mohammad-Jahed Farajzadeh ◽  
Shahriar Alipour ◽  
Alireza Abhari ◽  
Jafar Farhadi ◽  
...  

2021 ◽  
Vol 59 (2) ◽  
pp. 173-183
Author(s):  
T. A. Lisitsyna ◽  
G. A. Davydova ◽  
Z. S. Alekberova ◽  
R. G. Goloeva ◽  
L. A. Katargina ◽  
...  

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.


Rheumatology ◽  
2020 ◽  
Vol 59 (12) ◽  
pp. 3971-3979
Author(s):  
Tim B van der Houwen ◽  
Willem A Dik ◽  
Marco Goeijenbier ◽  
Manizhah Hayat ◽  
Nicole M A Nagtzaam ◽  
...  

Abstract Objectives To investigate whether the auto-inflammatory nature and the pathergic reaction in Behçet’s disease (BD) are driven by a disturbed toll-like receptor (TLR) response. Methods We compared both TLR expression by flow-cytometry and TLR response by stimulation assay in 18 BD patients (both pathergy positive and pathergy negative) with 15 healthy controls. Results Expression of TLR1 and 2 was significantly elevated in B-lymphocytes of BD patients compared with healthy controls. TLR1, 2 and 4 were significantly more highly expressed in both CD4+ and CD8+ T-lymphocytes of BD patients. Granulocytes of BD patients displayed significantly higher expression of TLR1, 2, 4 and 6. TLR2, 4 and 5 expression was significantly increased on classical monocytes of BD patients. Intermediate monocytes of BD patients showed an increase in expression of TLR2. Furthermore, TLR2 and 5 were significantly more highly expressed in non-classical monocytes of BD patients. In pathergy positive patients, TLR5 was even more highly expressed compared with pathergy negative patients on B- and T-lymphocytes and granulocytes. Furthermore, TLR2 and 5 showed an elevated TNF-α response to stimulation with their cognate ligands. Conclusion Immune cells of BD patients overexpress TLR1, 2, 4, 5 and 6. Furthermore, after stimulation of TLR2 and 5, BD patients demonstrate a more potent TNF-α response. Although this is a small cohort, in the pathergy positive patients, TLR5 expression is even further augmented, suggesting that a microbial (flagellin) or damage (HMGB1) associated signal may trigger the exaggerated immune response that is characteristic for the pathergy phenomenon in BD. In conclusion, these results point to an exaggerated TLR response in the auto-inflammatory nature of BD.


2013 ◽  
Vol 4 ◽  
Author(s):  
Ouahiba Khaib Dit Naib ◽  
Mourad Aribi ◽  
Aicha Idder ◽  
Amel Chiali ◽  
Hakim Sairi ◽  
...  

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