Person: DİRESKENELİ, RAFİ HANER
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DİRESKENELİ
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RAFİ HANER
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Publication Open Access Biologic treatments in Behcet's disease(AVES, 2021-11-22) ALİBAZ ÖNER, FATMA; Alibaz-Oner, Fatma; Direskeneli, HanerBehcet's disease (BD) significantly increases morbidity and mortality, especially in young men. While vascular involvement is the most frequent cause of mortality, ocular involvement, which can cause visual loss, is the most important cause of morbidity in BD. Immunosuppressive treatment is the mainstay for major organ involvement. However, despite optimal immunosuppressive treatment, relapses and disease-related damage develop in a subgroup of patients, especially among those with ocular or vascular involvement. With the recent understanding of the immuno-pathogenesis, biologic treatments targeting potential pathogenic cells, cytokines or pathways are better optimized in BD. Data from large series showed that tumor necrosis factor-alpha inhibitors and interferon-alpha are effective and safe treatment options for the treatment of refractory and major organ involvement, such as ocular, neurologic, vascular, and gastrointestinal. Anakinra and ustekinumab also seem to be promising agents for refractory mucocutaneous disease. IL-1 inhibitors and tocilizumab may be alternatives for the treatment of patients with refractory eye involvement. Still, randomized controlled trials of biologic agents, especially for the treatment of major organ involvement, are insufficient, and further prospective, long-term follow-up studies are needed to clarify the efficacy, safety, and optimal treatment duration of biologic agents in BD.Publication Open Access Anti-MHC autoimmunity in Behcet's disease: T cell responses to an HLA-B-derived peptide cross-reactive with retinal-S antigen in patients with uveitis(BLACKWELL SCIENCE LTD, 2001-12-24) DİRESKENELİ, RAFİ HANER; Kurhan-Yavuz, S; Direskeneli, H; Bozkurt, N; Ozyazgan, Y; Bavbek, T; Kazokoglu, H; Eksioglu-Demiralp, E; Wildner, G; Diedrichs-Mohring, M; Akoglu, TImmune response to retinal autoantigens plays a central role in the pathogenesis of uveitis. A synthetic peptide (B27PD) from a common sequence of various HLA-B molecules associated with uveitis, such as HLA-B27 and 51, which shares amino acid homologies with a retinal-S antigen (S-Ag)-derived peptide (PDSAg), was shown to be immunogenic in human and experimental uveitis in the rat. In this study we investigated T cell responses to B27PD and PDSAg in patients with Behcet's disease and posterior uveitis (BD-posterior uveitis; n = 33) in comparison with non-Behcet anterior uveitis (AU, n = 14), Behcet's patients without uveitis (BD, n = 15) and healthy controls (HC, n = 32) in a 6-day proliferation assay. Patients with BD and posterior uveitis had significantly higher responses (stimulation index (SI) 2.8 +/- 1.3) than those with AU (SI 1.5 +/- 0.4), BD without uveitis (SI 1.1 +/- 0.4) and HC (SI 1.1 +/- 0.6) for B27PD (P < 0.0001). Responses to PDSAg were also higher in BD with posterior uveitis patients (SI 3.3 +/- 1.6) than AU (SI 1.5 +/- 0.4), BD without uveitis (SI 1.2 +/- 0.3) and HC (SI 1.1 +/- 0.6) (P < 0.0001). A significant correlation between the responses to PDSAg and B27PD (r = 0.56, P < 0.001) was observed. Elevated levels of IL-2 and tumour necrosis factor-alpha were also observed in culture supernatants obtained from peripheral blood mononuclear cells after stimulation with the peptides, but no correlation was found between the proliferative responses and cytokine levels. These results suggest that cellular immunity to cross-reactive HLA-B and S-Ag-derived peptides might play a role in the pathogenesis of posterior uveitis in BD.Publication Open Access Autoimmunity vs autoinflammation in Behcet's disease: do we oversimplify a complex disorder?(OXFORD UNIV PRESS, 2006-08-18) DİRESKENELİ, RAFİ HANER; Direskeneli, H.Behcet's disease (BD) is a systemic inflammatory disorder with a diverse spectrum of clinical manifestations including mucocutaneous, ocular, vascular, gastrointestinal, musculoskeletal and central nervous system involvement [1]. A complex genetic background leading to a pro-inflammatory, innate-immune-system-derived activation perpetuated by adaptive immune responses against enviromental and auto-antigens is accepted to be the hallmark of BD [2]. This review aims to make an in-depth critical analysis of current data for recent controversies on the role of innate immune system vs autoimmunity in BD [3-5].Publication Open Access Pro-inflammatory cytokine and caspase-1 responses to pattern recognition receptor activation of neutrophils and dendritic cells in Behcet's disease(OXFORD UNIV PRESS, 2013-05-01) MUMCU, GONCA; Ture-Ozdemir, Filiz; Tulunay, Aysin; Elbasi, Mehmet Onur; Tatli, Imren; Maurer, Anne-Marie; Mumcu, Gonca; Direskeneli, Haner; Eksioglu-Demiralp, EmelObjective. Activated innate immunity is implicated in the pathogenesis of Behcet's disease (BD). To clarify the mechanisms of innate immune responses, we investigated inflammasome activation in dendritic cells (DCs) and neutrophils, following stimulation with two different pattern recognition receptors (PRRs) RIG-1-like (RLR) and NOD-like (NLR) in patients with BD. Methods. Sixteen active BD patients with mucocutaneous lesions and 17 healthy controls (HCs) were included in this study. DCs were generated from monocytes. DCs and isolated neutrophils were activated by RLR and NLR ligands. Caspase-1 activation and expression of p38 and RIP2 were determined by flow cytometry. Levels of IL-1 beta, IL-6, TNF-alpha, IFN-alpha and IL-18 in culture supernatants were measured by ELISA. Results. Activation of caspase-1 following intracellular PRR stimulation was found to be of similar levels in DCs and neutrophils of BD patients compared with HCs. However, activation of DCs from BD patients to NOD2 stimulus measured by the expression of RIP2 and p38 as well as IL-18 levels was found to be slightly defective (P < 0.05). In neutrophil cultures, IL-6 levels were lower in response to all stimuli in patients with BD compared with HCs (P < 0.01). Conclusion. Inflammasome formation following stimulation with NOD1/NOD2 and RIG measured by caspase-1 activation, cytokine levels and expression of RIP2 and p38 seems to be functionally normal in DCs and neutrophils of BD patients, although slightly defective responses in some pathways and cytokine levels were observed. These results may suggest that caspase-1-independent pathways such as toll-like receptors may be more prominent in BD pathogenesis.Publication Open Access Immune and inflammatory gene expressions are different in Behcet's disease compared to those in Familial Mediterranean Fever(AVES, 2017-01-11) DİRESKENELİ, RAFİ HANER; Ozdemir, Filiz Ture; Demiralp, Emel Eksioglu; Aydin, Sibel Z.; Atagunduz, Pamir; Ergun, Tulin; Direskeneli, HanerObjective: The immune classification of Behcet's disease (BD) is still controversial. In this study, we aimed to compare the immune/inflammatory gene expressions in BD with those in familial Mediterranean fever (FMF), an autoinflammatory disorder with innate immune activation. Material and Methods: CD4+ T cells and CD14+ monocytes were isolated from the peripheral blood mononuclear cells of Behcet's disease patients (n=10), FMF (n=6) patients, and healthy controls (n=4) with microbeads, and then, the mRNA was isolated. The expressions of 440 genes associated with immune and inflammatory responses were studied with a focused DNA microarray using a chemiluminescent tagging system. Changes above 1.5-fold and below 0.8-fold were accepted to be significant. Results: In BD patients, in the CD4+ T-lymphocyte subset, interleukin 18 receptor accessory protein (1.7-fold), IL-7 receptor (1.9-fold), and prokineticin 2 (2.5-fold) were all increased compared to those in FMF patients, whereas chemokine (C-X3-C motif) receptor-1 (CX3CR1) (0.7-fold) and endothelial cell growth factor-1 (0.6-fold) were decreased. In the CD14+ monocyte population, the V-fos FBJ murine osteosarcoma viral oncogene homolog (1.5-fold), Interleukin-8 (IL-8) (2.1-fold), and Tumor Necrosis Factor alpha (TNF-alpha) (1.8-fold) were all increased, whereas the chemokine (C-C motif) ligand 5 (CCL5) (0.6-fold), C-C chemokine receptor type 7 (0.6-fold), and CX3CR1 (0.7-fold) were decreased, again when compared to those in FMF. Compared to healthy controls in the CD4+ T-lymphocyte population, in both BD and FMF patients, pro-platelet basic protein and CD27 had elevated expression. In BD and FMF patients, 24 and 19 genes, respectively, were downregulated, with 15 overlapping genes between both disorders. In the CD14+ monocytes population, chemokine (C-C motif) receptor-1 (CCR1) was upregulated both in BD and FMF patients compared to that in the controls, whereas CCL5 was downregulated. Conclusion: Immune and inflammatory gene expressions seem to be variable in both the innate (CD14+) and adaptive (CD4+) immune responses in BD and FMF patients compared to those in controls, suggesting differences in immune regulation between the two disorders.Publication Open Access Oral ulcer activity in Behcet's disease: Poor medication adherence is an underestimated risk factor(AVES, 2017-06-12) ALİBAZ ÖNER, FATMA; Mumcu, Gonca; Alibaz-Oner, Fatma; Oner, Sibel Yilmaz; Ozen, Gulsen; Atagunduz, Pamir; Inanc, Nevsun; Koksal, Leyla; Ergun, Tulin; Direskeneli, HanerObjective: The aim of this study was to evaluate the relationship between oral ulcer activity and medication adherence according to gender in Behcet's disease (BD) patients. Material and Methods: The study group included 330 BD patients (F/M: 167/163, mean age: 38.5 +/- 10.5 years). Oral ulcer activity and medication adherence were evaluated in the previous month. Medication adherence was evaluated using the 8-item Morisky Medication Adherence Scale (MMAS-8) having a score range of 0 to 8 with high scores indicating better adherence. Low adherence was defined as < 6 points on MMAS-8. Results: Over half of the group had active oral ulcers (n= 219, 66.4%) within the month preceding the visit. The number of oral ulcers was significantly higher in female patients with low medication adherence (2.39 +/- 3.24) than in the rest of the female group (1.28 +/- 2.05; p= 0.023). Although a similar trend was also observed in male patients (2.14 +/- 3.3 vs. 1.81 +/- 2.31), a significant relationship was not observed (p= 0.89). The frequency of medication intake per day was lower in patients with high medication adherence than in the rest of the study group (p= 0.04). Conclusion: Low medication adherence is a hidden risk factor in the management of BD. Poor adherence was associated with oral ulcer activity in female BD patients.Publication Open Access The assessment of contributing factors to oral ulcer presence in Behcet's disease: Dietary and non-dietary factors(AVES, 2018-11-27) AKSOY, AYSUN; Iris, Merve; Ozcikmak, Ezgi; Aksoy, Aysun; Alibaz-Oner, Fatma; Inanc, Nevsun; Ergun, Tulin; Direskeneli, Haner; Mumcu, GoncaObjective: The aim of this study was to assess the contributing factors for oral ulcer activity in Behcet's disease (BD). Methods: Ninety-two patients with BD (F/M: 42/50, mean age: 38.7 +/- 10.02 years) participated in this cross-sectional study. Data regarding disease-related factors, smoking patterns, and self-reported dietary/non-dietary triggering factors for oral ulcer activity were collected by a questionnaire. Treatment protocol was categorized as mild and intensive groups associated with organ involvements. Results: A mild treatment protocol was more common in females (52.4% vs 20%) than in males (p=0.002). During the last three months, the number of oral ulcers in female patients was higher in the mild treatment group (6.4 +/- 6.5) than in the intensive treatment group (3.3 +/- 4.9) (p=0.045). In patients with active oral ulcers (n=63), rate of being a non-smoker was also higher in females (86.7% vs 63.6%) than in males. Daily frequency of tooth brushing was 1.2 +/- 0.8 in patients with BD, and was higher in females (1.5 +/- 0.9 vs 0.9 +/- 0.6) (p=0.001). Stress and fatigue (78.3%) were reported as the most frequent triggering factors for oral ulcer presence in patients with BD. A total of 148 different dietary factors associated with oral ulcer presence were reported in the study. Conclusion: A mild treatment protocol and being a non-smoker were found to be the contributing factors associated with oral ulcer activity in patients with BD. Being motivated for oral hygiene and being non-smokers were positive health behaviors observed in females. Irrespective of gender, stress and fatigue were defined as the most common self-reported triggering factors for oral ulcer presence in BD. In addition, the roles of some dietary factors were also reported.Publication Open Access Pulmonary arterial wall thickness is increased in Behçet's disease patients with major organ ınvolvement: Is it a sign of severity?(2023-03-01) KOCAKAYA, DERYA; DİRESKENELİ, RAFİ HANER; ALİBAZ ÖNER, FATMA; Ağaçkıran S. K., Sünbül M., Doğan Z., Kocakaya D., Kayacı S., Direskeneli H., Alibaz-Oner F.Objectives Behcet\"s disease (BD) is a unique systemic vasculitis mainly involving veins, in contrast to other vasculitides. Prior studies have shown that pulmonary arteries (PAs) have a similar structure to systemic veins. In this study we aimed to assess PA wall thickness by transthoracic echocardiography (TTE) in BD patients compared with healthy controls (HCs) and patients with non-inflammatory pulmonary embolism (NIPE). Methods Patients with BD (n = 77) and NIPE (n = 33) and HCs (n = 57) were studied. PA wall thickness was measured from the mid-portion of the main PA with TTE by two cardiologists blinded to cases. Results PA wall thickness was significantly lower in HCs [3.6 mm (s.d. 0.3)] compared with NIPE [4.4 mm (s.d. 0.5)] and BD [4.4 mm (s.d. 0.6)] (P < 0.001 for both). PA wall thickness was similar between BD and NIPE (P = 0.6). Among patients with BD, PA wall thickness was significantly higher in patients with major organ involvement compared with mucocutaneous limited disease [4.7 mm (s.d. 0.4) vs 3.7 (0.4), P < 0.001], HCs and NIPE (P < 0.001 and P = 0.006, respectively). PA wall thickness was comparable between patients with vascular and non-vascular major organ involvement [4.6 mm (s.d. 0.5) vs 4.7 (0.3), P = 0.3]. Conclusion We observed that PA wall thickness was significantly higher in BD with major organ involvement compared with patients with only mucocutaneous limited disease, HCs and NIPE. These results suggest that increased PA wall thickness may be a sign of severe disease with major organ involvement in BD.Publication Open Access Oral health is impaired in Behcet's disease and is associated with disease severity(OXFORD UNIV PRESS, 2004-06-01) MUMCU, GONCA; Mumcu, G; Ergun, T; Inanc, N; Fresko, I; Atalay, T; Hayran, O; Direskeneli, HObjectives. This study aimed to investigate the oral health of Turkish patients with Behcet's disease (BD) and whether it is associated with the disease course. Methods. One hundred and twenty patients with BD, 35 patients with recurrent aphthous stomatitis (RAS) and 65 healthy Turkish controls (HC) were included in the study. Oral health was investigated by indices applied in a BD out-patient clinic. Results. The mean scores of plaque, sulcus bleeding and gingival indices, probing depth and the number of extracted teeth were observed to be higher in patients with BD and RAS compared to HC (P<0.05). In the linear regression analysis, plaque index score was associated with the presence of oral ulcers and male gender. An elevated plaque index score was observed to be a significant risk factor for increased severity score in patients with BD in the logistic regression analysis (P = 0.034). Conclusions. Oral health is impaired in BD and associated with disease severity. Improvement of the oral health of BD patients may affect their disease course, leading to a better prognosis.