Person: ERGUN, SAFİYE ATLAS TÜLİN
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ERGUN
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SAFİYE ATLAS TÜLİN
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Publication Open Access Oligoclonal T cell expansions in patients with Behçet's disease(2001-12-24) DİRESKENELİ, RAFİ HANER; ERGUN, SAFİYE ATLAS TÜLİN; Direskeneli, H; Eksioglu-Demiralp, E; Kibaroglu, A; Yavuz, S; Ergun, T; Akoglu, TBehçet's disease (BD) is a multisystem disorder with oral and genital ulcers, mucocutaneous, ocular, joint, vascular and central nervous system involvement. In this study, the peripheral T cell repertoire was analysed in patients with BD with MoAbs against T cell receptor (TCR) Vβ gene products in CD4+ and CD8+ T cell compartments, and these were compared with rheumatoid arthritis (RA) patients and healthy controls (HC). In the CD4+ T cell compartment, oligoclonal TCR Vβ expression was observed in 56% of BD (10/18), 71% of RA (5/7) patients and 21% (3/14) of HC. In the CD8+ T cell group 50% of BD (9/18), 57% of RA patients and 28% of HC (4/14) had an oligoclonal TCR repertoire. An increase of TCR Vβ5.1 subset was observed in five BD patients among CD8+ T cells. Other elevations of TCR Vβ subsets were heterogeneously distributed with one to three different Vβ subsets. Our results suggest an antigen-driven oligoclonal increase of T cells in BD. There was no overall increase in any Vβ group to suggest a superantigen effect. Analysis of the responsible antigens causing the increase in T cell subsets may give insights into the aetiopathogenesis of BD and immunomodulation of these T cells may lead to new treatments.Publication Metadata only Femoral vein wall thickness measurement: A new diagnostic tool for Behcet's disease(OXFORD UNIV PRESS, 2021) ALİBAZ ÖNER, FATMA; Alibaz-Oner, Fatma; Ergelen, Rabia; Yildiz, Yasin; Aldag, Mustafa; Yazici, Ayten; Cefle, Ayse; Koc, Ertan; Esen, Bahar Artim; Mumcu, Gonca; Ergun, Tulin; Direskeneli, HanerObjectives. Diagnosing Behcet's disease (BD) is a challenge, especially in countries with a low prevalence. Recently, venous wall thickness (VWT) in lower extremities has been shown to be increased in BD patients. In this study, we aimed to investigate the diagnostic performance of common femoral vein (CFV) thickness measurement in BD and whether it can be used as a diagnostic tool. Methods.. Patients with BD (n=152), ankylosing spondylitis (n=27), systemic vasculitides (n=23), venous insufficiency (n=29), antiphospholipid syndrome (APS; n=43), deep vein thrombosis due to non-inflammatory causes (n=25) and healthy controls (n=51) were included in the study. Bilateral CFV thickness was measured with ultrasonography by a radiologist blinded to cases. Results. Bilateral CFV thickness was significantly increased in BD compared with all control groups (P < 0.001 for all). The area under the receiver operating characteristic curve for bilateral CFV thicknesses in all comparator groups was >0.95 for the cut-off value (0.5 mm). This cut-off value also performed well against all control groups with sensitivity rates >90%. The specificity rate was also >80% in all comparator groups except APS (positive predictive value: 79.2-76.5%, negative predictive value: 92-91.8% for right and left CFV, respectively). Conclusion. Increased CFV thickness is a distinctive feature of BD and is rarely present in healthy and diseased controls, except APS. Our results suggest that CFV thickness measurement with ultrasonography, a non-invasive radiological modality, can be a diagnostic tool for BD with sensitivity and the specificity rates higher than 80% for the cut-off value >= 0.5mm.Publication Metadata only Behcet's disease in patients with chronic myelogenous leukemia: Possible role of interferon-alpha treatment in the occurrence of Behcet's symptoms(SPRINGER VERLAG, 1997) DİRESKENELİ, RAFİ HANER; BudakAlpdogan, T; Demircay, Z; Alpdogan, O; Direskeneli, H; Ergun, T; Bayik, M; Akoglu, TTwo patients with chronic myelogenous leukemia (CML) who developed characteristic features of Behcet's disease (ED) during alpha-interferon (IFN-alpha) treatment and another patient who had a diagnosis of ED preceding CML are presented. In the first two patients, features of ED appeared 6 months after the initiation of IFN-alpha treatment; they included recurrent oral aphthae, genital ulceration, arthritis, folliculitis, and a positive skin pathergy test. The third patient, however, had a diagnosis of Behcet's disease 4 years before diagnosis of Philadelphia-positive CML. We prospectively examined the skin pathergy reaction in a group of patients with CML, multiple myeloma, and hairy cell leukemia both before and after IFN-alpha treatment and found two additional patients with CML who developed a positive skin pathergy test following IFN-alpha treatment.Publication Open Access Common femoral vein thickness measurement as a diagnostic test in incomplete behcet's disease(2022-06-01) ALİBAZ ÖNER, FATMA; ERGELEN, RABİA; ERGUN, SAFİYE ATLAS TÜLİN; DİRESKENELİ, RAFİ HANER; Alibaz-Oner F., Ergelen R., Temiz F., Agackiran S. K. , Soydemir E., Ergun T., DİRESKENELİ R. H.Publication Metadata only Thalidomide has both anti-inflammatory and regulatory effects in Behcet's disease(SPRINGER, 2008) DİRESKENELİ, RAFİ HANER; Direskeneli, H.; Ergun, T.; Yavuz, S.; Hamuryudan, V.; Eksioglu-Demiralp, E.Thalidomide is shown to be an effective treatment for mucocutaneous symptoms of Behcet's disease (BD). In this study, the effects of thalidomide on peripheral blood mononuclear cells were investigated ex vivo. In an open prospective study, ten patients were given 200 mg/day thalidomide for 12 weeks and cluster of differentiation 4 (CD4), CD8, CD11a, CD11b, CD16, CD18, CD28, CD44, CD45RO, CD45RA, CD56, CD120a and gamma delta+ T cells were analysed with flow cytometry at 0, 3, 7, 30 and 90 days. Two patients were excluded from the analysis for attacks of uveitis within the first 2 weeks. At day 7, tumour necrosis factor-alpha (TNF-alpha) receptor+ (CD120a; 12% vs 5%), CD8/CD11b+ (12% vs 6%) and CD16/CD56+ (16% vs 9%) cells decreased in BD patients compared to day 0. On the other hand, CD4+CD45RO+ T cells (24% vs 34%) at day 30 and gamma delta+ T cells (11% vs 21%) at day 90 increased after treatment. These results suggest that thalidomide tends to decrease TNF-alpha receptor levels, CD8/CD11b+ T cells and natural killer cells in early treatment and increases CD4+CD45RO+ memory T and gamma delta+ T cells later in BD.Publication Metadata only Oral health is a mediator for disease severity in patients with Behcet's disease: A multiple mediation analysis study(WILEY, 2019) AKSOY, AYSUN; Yay, Meral; Celik, Zulal; Aksoy, Aysun; Alibaz-Oner, Fatma; Inanc, Nevsun; Ergun, Tulin; Direskeneli, Haner; Mumcu, GoncaObjectivesThe aim of the study was to examine whether oral health as an infection focus could mediate disease course in patients with Behcet's disease (BD). MethodsIn the study, oral health of 194 BD patients was examined at baseline and follow-up periods. The reasons for last dental visits were recorded as tooth extraction or regular control visits/planned treatments at the end of follow-up period. The Behcet's disease severity score was calculated with higher scores indicating a more severe course. Mediation analysis was carried out to assess the effects of oral health on disease severity score at follow-up period in the study. ResultsDental and periodontal indices were found to be higher at follow-up visit compared to those of baseline (P<0.05). Disease severity score was found to be higher in males (5.32.4) compared to females (4.4 +/- 2.5) in the whole group (P=0.005). Moreover, patients having tooth extraction at their last dental visit and patients with dental caries had a more severe disease course (5.4 +/- 2.4; 5.5 +/- 2.5) compared to others (4.2 +/- 2.3; 4.4 +/- 2.4; P<0.0001). In multiple mediation analysis, disease severity score was a dependent variable and was directly mediated by male gender (B=-0.8822, P=0.0145) and indirectly mediated through the presence of dental caries (B=0.9509 P=0.0110) and need of tooth extraction (B=0.8758, P=0.0128). ConclusionBoth presence of dental caries and need of tooth extraction were observed to be effective mediators for a more severe disease course in BD. Therefore, better oral health should be aimed to eliminate microbial factors, which are a part of pathogenic processes.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 Atypical presentations of eosinophilic fasciitis(MEDKNOW PUBLICATIONS & MEDIA PVT LTD, 2016) SALMAN, ANDAÇ; Ergun, Tulin; Seckin, Dilek; Salman, Andac; Ocak, Esra Sarac; Yucelten, Ayse Deniz; Direskeneli, Haner; Demirkesen, Cuyan; Ekinci, Gazanfer; Bayik, MahmutEosinophilic fasciitis is an uncommon connective tissue disease that may mimic and overlap with other sclerosing disorders such as morphea and lichen sclerosus. Herein, we report four patients (two men and two women, aged 16-64 yeas) with eosinophilic fasciitis. There was overlap with both morphea and lichen sclerosus in 2 patients and with morphoea alone in 1 patient. Magnetic resonance imaging (MRI) was used for diagnosis in three patients and for assessing treatment response in one patient. Eosinophilic fasciitis may co-exist with morhoea and lichen sclerosus. In view of the overlapping clinical and histopathological features of these disorders, MRI may be helful in delineating the conditions by detecting involvement of fascia.Publication Metadata only Salivary levels of antimicrobial peptides Hnp 1-3, Ll-37 and S100 in Behcet's disease(PERGAMON-ELSEVIER SCIENCE LTD, 2012) MUMCU, GONCA; Mumcu, Gonca; Cimilli, Hale; Karacayli, Umit; Inanc, Nevsun; Ture-Ozdemir, Filiz; Eksioglu-Demiralp, Emel; Ergun, Tulin; Direskeneli, HanerBackground: Oral ulcer is the cardinal clinical sign and increased neutrophilic activity is a part of the pathogenesis in Behcet's disease (BD). Saliva, as a part of the innate immune response, contains antimicrobial peptides (AMPs) that are derived from both oral epithelial cells and neutrophils. The aim of this study was to investigate the associations between salivary levels of AMPs HNP 1-3, LL-37 and S100 and disease course in patients with Behcet's disease (BD). Methods: Fifty-three patients with BD and 44 healthy controls (HC) were included in the study. Disease severity score reflecting organ involvement was calculated. Salivary HNP 1-3, LL-37 and S100 levels were measured in unstimulated saliva samples by ELISA. Results: Salivary HNP 1-3 and S100 levels in BD patients (2715.2 +/- 1333.4 mu g/ml and 430.6 +/- 203.9 mu g/ml) were significantly higher compared to HC (1780.6 +/- 933.2 mu g/ml and 365.3 +/- 84.7 mu g/ml) (p = 0.000 and p = 0.004, respectively). Although LL-37 levels were also higher in BD than HC (190.9 +/- 189.1 vs 143.1 +/- 128.9 ng/ml), no significant difference was observed (p = 0.53). Salivary HNP 1-3 and LL-37 levels were associated with the severity of BD (mild disease: 1975.1 +/- 1174.2 mu g/ml and 115.9 +/- 109.4 ng/ml vs severe disease: 2955.7 +/- 1305.6 mu g/ml and 215.3 +/- 203.8 ng/ml, p = 0.020 and p = 0.031, respectively). Salivary LL-37 levels also correlated with the number of monthly oral ulcers (r = 0.5 p = 0.000). Conclusion: An increase in salivary HNP 1-3 and S100 levels might be associated with enhanced local and systemic innate responses in BD. (C) 2011 Elsevier Ltd. All rights reserved.Publication Metadata only The Assessment of Presenteeism and Activity Impairment in Behcet's Syndrome and Recurrent Aphthous Stomatitis: A multicentre Study(2021) ALİBAZ ÖNER, FATMA; Karacayli, Umit; Adesanya, Adebowale; Aksoy, Aysun; Belem, Joice M. F. M.; Cardin, Natália Borges; Sarı, Fatma Busra; Beyhan, Tuğba Emine; Çelik, Zülal; Karacayli, Ceren; Alibaz-Öner, Fatma; Inanç, Nevsun; Ergun, Tülin; Yay, Meral; Madanat, Wafa; Silva de Souza, Alexandre Wagner; Fortune, Farida; Direskeneli, Haner; Mumcu, GoncaOBJECTIVE: To evaluate key factors for Presenteeism and Activity impairment in multinational patients with Behçet's syndrome (BS) and recurrent aphthous stomatitis (RAS). METHODS: In this cross-sectional study, 364 BS patients from Jordan, Brazil, the United Kingdom and Turkey and 143 RAS patients from the United Kingdom and Turkey were included. Work Productivity Activity Impairment (WPAI) scale was used for Presenteeism and Activity impairment. Mediation analyses were performed to evaluate both direct and indirect causal effects. RESULTS: Presenteeism score was higher in active patients with genital ulcers and eye involvement as well as patients with comorbidities and current smokers than the others in BS (p< 0.05). In RAS, Presenteeism score was elevated by oral ulcer activity in the direct path (p= 0.0073) and long disease duration as a mediator in the indirect path (p= 0.0191).Patients with active joint involvement had poor scores in Absenteeism, Presenteeism, Overall impairment and Activity impairment compared with those of inactive patients (p < 0.05). Using mediation analysis, the Activity impairment score was directly mediated by joint activity (p = 0.0001) and indirectly mediated through oral ulcer-related pain in BS (p = 0.0309). CONCLUSION: In BS, Presenteeism was associated with disease activity, presence of comorbidities and being a current smoker, whereas in RAS, Presenteeism was associated with oral ulcer activity and increased length of the disease. Moreover, Activity impairment was adversely affected by joint activity and oral ulcer related pain in BS. Patients need to be empowered by using appropriate treatment strategies in their working environment and daily life.