Inactive Behçet's Disease Patients Research Articles

Effect of different cytokines in combination with IL-15 on the expression of activating receptors in NK cells of patients with Behçet's disease.

Behçet's disease (BD) is a systemic, autoinflammatory, chronic disorder which affects various parts of the body in genetically susceptible individuals. BD has a multi-factorial etiopathogenesis which encompasses both innate and adaptive arms of immunity. NK cells, which kill virus-infected or malign cells and provide interaction between adaptive and innate immune system, are also known to involve in the pathogenesis of autoimmune/autoinflammatory diseases including BD. NK cells function in immune responses via the signals obtained from surface-expressed activating and inhibitory receptors. In this study, we aimed to explore NK cell activation status by measuring the levels of activation marker CD69 and activating receptors NKG2D, NKp30, and NKp46 as well as proliferative and cytotoxic capacities in response to stimulation with interleukin (IL)-15-combined cytokines in BD patients. CD4+ and CD8+ T cell responses were also evaluated to compare with those of NK cells. As a result, the expression of activating receptors on NK cells was demonstrated to be varied among patients with active and inactive BD and healthy controls. The proliferation levels of NK cells were elevated in BD patients, especially in inactive phase of disease compared to healthy controls. Additionally, CD107a levels of inactive BD patients were detected to be lower in comparison with healthy controls and active BD patients. These findings suggest that BD patients in active and inactive phases display different activation status of NK cells which indicate NK cells might be associated with immune attacks and remissions during the course of BD.

IL-17A and IFN-γ are Up-regulated in CD4 and γδ T Cells in Active Behcet's Disease Patients

Involvement of γδ T cells is implicated in the pathogenesis of Behçet's disease (BD) as a bridge between innate and adaptive responses. IL-17 and IL-22 have also been shown to participate in the BD pathogenesis in addition to IFN-γ. Mainly CD4+ T cells are investigated previously for the production of these inflammatory cytokines. In this study, the role of γδ T cells in cytokine-related mechanisms was evaluated in BD in comparison to CD4+ T cells. Surface expression of markers for functional states of both CD4+ and γδ T cells were compared in ex vivo samples collected from patients with BD and healthy controls (HC).Sixteen active BD (a-BD), 9 inactive BD (i-BD) patients and 25 HC were investigated. The expression of CD161, CCR6 as markers for IL-17 producing cells were analyzed on γδ and CD4+ T cells. IFN-γ, IL-17A, IL-22, as well as CD107a (LAMP1) and CD16 (FcγRIII) were evaluated in both cell subtypes after in vitro stimulation.Only IFN-γ production was increased in γδ T cells of a-BD patients. There was no difference in increase of CD107a or decrease of CD16 surface expression on γδ T cells upon stimulation between the groups. Ex vivo IL-17A and both IL-17A/IFN-γ production and expression of CD161, CCR6 by CD4+ T cells were increased in a-BD.Along with CD4+ T cells, γδ T cells have complementary roles in cytokine production in BD. Higher IFN-γ production of γδ T cells suggests the role of an environmental triggers in BD pathogenesis, whereas IL-17 related activity is mainly provided by CD4+ T cells.

Serum Cortistatin Levels in Patients with Ocular Active and Ocular Inactive Behçet Disease

ABSTRACT Purpose To evaluate serum cortistatin (CST) levels in patients with ocular active and ocular inactive Behçet disease (BD) and its relationship with disease activity. Methods 24 BD patients with ocular active, 24 BD patients with ocular inactive patients and 24 healthy control subjects were included in the study. Results In ocular active and ocular inactive BD patients and healthy control subjects, the mean serum CST levels were 4.38 ± 1.63ng/ml, 5.46 ± 1.81ng/ml and 7.56 ± 1.73ng/ml, respectively. ESR, serum CRP, CST levels and NLR were significantly different between the groups (p < 0.001 for all). The CST levels were similar between ocular active and inactive BD patient groups (p = 0.197). ESR, CRP and NLR were significantly higher in ocular active BD patients compared to ocular inactive BD patients and healthy control subjects (p < 0.05 for all). Conclusion Serum CST level was significantly lower in BD patients. CST may be a neuropeptide that plays a role in the pathogenesis of BD.

Th 9 cells in Behçet disease: Possible involvement of IL-9 in pulmonary manifestations

Behçet disease (BD) is a multisystemic disease some of whose manifestations are characterized by pulmonary involvements. The purpose of the study was to evaluate the level of T-helper type 9 (Th9) cells and the cytokine interleukin (IL)-9 in peripheral blood and in bronchoalveolar lavage (BAL) of patients with Behçet's disease (BD) affected by pulmonary manifestations. Nevertheless, until recently there have been no studies on its role in BD.The Th9 (CD4+IL-9+T) cell, transcription factor PU.1 and IL-9 mRNA levels, as well as serum and BAL IL-9 concentration, were measured in BD patients and healthy controls.The Th9 cell percentage and absolute number, PU.1 and IL-9 expression levels of BD patients were all increased significantly compared with the control group. Absolute number of Th9 cells was particularly increased in patients with active BD compared to inactive BD patients. The levels of IL-9 associated to Th9 expression depended on BD severity. These parameters were markedly expressed in the BAL of BD patients with pulmonary manifestations. IL-17 and the epithelial inflammatory cytokine TSLP were significantly correlated to IL-9 levels. This cytokine trio decreased in inactive BD patients after corticosteroïd treatment. In addition, IL-9 levels were correlated to CD4+ IL-9+ cells in BAL and in PBMCs. LPS stimulated PBMCs and macrophages induced increased secretion of IL-9 and the encoding transcription factors PU.1 and IRF4.In conclusion, the expansion of the Th9 cell subset, up-regulation of the PU.1 transcription factor and increased secretion of the IL-9 cytokine may contribute to the pathogenesis of BD, which may be supported by the increased release of IL-17 and TSLP. We provide evidence that Th9 T cells are increased in BD patients with pulmonary manifestations. This suggests an important role of IL-9 in the pathogenesis of BD particularly in patients suffering from lung involvement.

Role of Serum miR-181b, Proinflammatory Cytokine, and Adhesion Molecules in Behçet's Disease.

Behçet's disease (BD) is a chronic multi-systemic inflammatory disease of uncertain pathogenesis and with no definitive diagnostic test. The aims of this study were to investigate serum levels of miR-181b in BD patients and to correlate this candidate biomarker with disease activity, cytokines, and adhesion molecules to identify new markers that can be used as a diagnostic tool for BD. Blood samples were collected from 96 participants who were classified according to their BD current activity form into 3 groups: healthy control, active BD, and inactive BD patients. MiR-181b was estimated by real-time polymerase chain reaction. However, high sensitive C-reactive protein (hs-CRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), E-selectin, and vascular cell adhesion molecule 1 (VCAM-1) levels were determined by enzyme-linked immunosorbent assay. Serum levels of miR-181b, hs-CRP, TNF-α, IL-6, E-selectin, and VCAM-1 were significantly higher in patients than in controls, but no significant difference was observed between the active and inactive BD groups. IL-6 was positively correlated with adhesion molecules, E-selectin, and VCAM-1. MiR-181b was positively correlated with hs-CRP, TNF-α, IL-6, and VCAM-1 in all subjects. In conclusion, miR-181b could play an important role in BD pathophysiology. MiR-181b could be utilized as potential biomarker for diagnosis and therapeutic targeting of BD. However, further studies with larger patient number are required to support these findings.

An evaluation of depression, anxiety and fatigue in patients with Behçet's disease.

Behçet's disease (BD) is a type of systemic vasculitis and inflammatory disease of unknown etiology, which is associated with fatigue and lower quality of life (QoL). The aim of this study was to assess the relationship between Behçet's Disease Current Activity Form (BDCAF) and Behçet's Disease Quality of Life (BDQoL), depression, anxiety and fatigue in Behçet's disease. We conducted a cross-sectional study of 155 BD patients and 107 healthy subjects in a single center over a 1year period. All participants completed the Multidimensional Assessment of Fatigue (MAF) questionnaire, and the Hospital Anxiety and Depression (HADS) scale. Disease activity in the BD patients was assessed using the BDCAF, and the physician's global assessment (PGA). BD patients also completed the BDQoL questionnaire. There was no significant difference in age and gender between the groups. BD patients had significantly higher HADS-anxiety (HADS-A), HADS-depression (HADS-D) and MAF scores than the healthy control group (P<0.05). BD patients with active disease had significantly higher MAF and HADS-A scores compared to inactive BD patients (P<0.05). MAF scores showed positive correlations with HADS-A, HADS-D, BDCAF and BDQoL. Fatigue and anxiety are common in clinically active BD patients compared with healthy control subjects and inactive BD patients.

Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in Behçet's disease: which and when to use?

Behçet's disease (BD) is an uncommon autoimmune/autoinflammatory disease. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were investigated in many diseases as a marker of inflammation. In this study, we investigated NLR and PLR in patients with BD as a marker of disease activity and its association with different clinical manifestations. The study included 23 BD patients; their mean age was (32.5 ± 6.76) and M:F ratio was 16:7. Complete blood picture was done for all patients. NLR and PLR were compared in both active and inactive BD patients and its relation with different clinical manifestations was assessed. NLR was higher in active BD patients than in inactive BD patients (P < 0.01). Although both NLR and PLR were correlated with Behçet's Disease Current Activity Form (BDCAF), the correlation of NLR with BDCAF was much stronger than that of PLR. NLR was associated with some mucocutaneous lesions. Both NLR and PLR were associated with articular and GIT manifestations, but also NLR showed more significant results. In our studied patients, both NLR and PLR were not informative about any ongoing ocular activity (P > 0.05). Both ratios were not affected by the presence of neurologic deficits nor previous vascular events (P > 0.05). NLR was superior to PLR as an indicator of disease activity. NLR was closely related to skin manifestations while PLR was not. In our study, both were not considered reliable in representing ocular activity.

Carotid artery stiffness in Behçet's disease.

Increased carotid arterial stiffness (CAS) is a predictor of subclinical early atherosclerosis as well as carotid intima-media thickness (cIMT). We aimed to determine CAS and cIMT in Behçet's disease (BD). BD (n=49) and rheumatoid arthritis (RA) (n=64) patients and healthy controls (HC) (n=40) were included in the study. cIMT was measured. CAS indices, including arterial compliance (AC), arterial distensibility (AD), Young's elastic modulus (YEM), Peterson's elastic modulus (Ep), and β stiffness index (βSI) were measured based on the diameter-pressure relationship. When compared to the HC group, the mean cIMT was significantly higher in the RA group (p=0.033), but it was not higher in the BD group. The CAS indices, including AD, AC, Ep, and βSI were not significantly different among the study groups. Moreover, the cIMT and CAS indices were not significantly different between active (n=20) and inactive BD patients, and these indices were not correlated with the scores of disease activity. AD, AC and Ep were significantly lower in the BD patients with a positive pathergy reaction than in those with a negative reaction. These results suggest that BD does not directly lead to arterial stiffness or to an increase in cIMT.

Procoagulant microparticles are increased in patients with Behçet's disease but do not define a specific subset of clinical manifestations.

Microparticles (MP) are considered a key component in the haemostatic response. Beyond their in vitro procoagulant properties, a number of pieces of evidence points to procoagulant MP as efficient effectors in the haemostatic response and as pathogenic markers of thrombotic disorders and vascular damage. The aim of the present study was to analyze the procoagulant activity of MP and its correlation with clinical manifestations focusing on vascular involvement in patients with Behçet's disease (BD). We analyzed 55 BD patients in inactive phase of the disease (26 men; mean age, 35 ± 15 years) of which 19 had previously suffered from thrombosis (deep venous thrombosis in 17 and ischemic stroke in 2), and 73 healthy controls matched for age and sex. Procoagulant MP were assessed by a functional assay. BD patients showed higher procoagulant MP values than controls (22.89 ± 15.74 nM versus 14.47 ± 7.34 nM; p < 0.0001). Conversely, we did not find differences in the levels of procoagulant MP according to the gender of patients (22.22 ± 16.23 nM for men versus 21.46 ± 16.47 for women; p = 0.846) or to previous and current treatments. Moreover, the plasmatic concentration of MP does not define any clinical phenotype and it was not related to the time of evolution of the disease. Although inactive BD patients had high values of procoagulant MP, they did not differentiate between BD patients with or without thrombosis.

FRI0448 BehÇEt's Disease and Periodontal Disease: Double-Disease Burden

BackgroundPeriodontal disease (PD) is a chronic bacterial infection of the supporting structures of the teeth. Behçet's Disease (BD) is a chronic multi-systemic inflammatory vasculitis. PD and BD have strong similarities...

CCL21 attenuates HSV-induced inflammation through up-regulation of CD8+ memory cells

CCR7 and its ligand, CCL21, are known to establish microenvironments for the initiation of immune responses in secondary lymphoid tissue. It has also been reported that CCR7 ligand gene-deleted mice have defects in lymphocyte homing. In addition, the injection of the CCR7 ligand was shown to induce the expression of memory T cells. In this study, we analyzed the expression of CCR7 and its ligand in HSV-induced Behçet's disease (BD)-like inflammation of mice. Additionally, plasmids containing the CCR7 ligand CCL19 or CCL21, pcDNA3.1-CCL19 or pcDNA3.1-CCL21, respectively, were injected into symptomatic mice, and changes in the population of memory T cells were determined. After administration of pcDNA3.1-CCL21, the frequencies of CD8+CD44+, CD8+CD62L− memory T cells were significantly up-regulated and the symptoms were not deteriorated when compared to the control vector injected group. Specifically, the difference in frequencies of CCR7+ peripheral blood mononuclear cells between active BD patients and inactive BD patients was similar to that of HSV-induced BD-like mice. These results suggest that CCR7, its ligand, and CD8+ memory cells are correlated with the regulation of BD symptoms.

Behçet's disease exhibits an increased osteopontin serum level in active stage but no association with osteopontin and its receptor gene polymorphisms

Osteopontin (OPN) and its receptors have been reported to be involved in a number of autoimmune and inflammatory diseases. This study was designed to analyze the OPN serum level in Behçet's disease (BD) and the association of gene polymorphisms of OPN and its receptors with BD. The serum level of OPN in active BD patients, inactive BD patients, and controls was assayed by enzyme-linked immunosorbent assay. Four single nucleotide polymorphisms (SNPs) of OPN and 4 SNPs of OPN receptors were genotyped in 318 BD patients and 313 controls using a polymerase chain reaction restriction fragment length polymorphism assay. The OPN level was significantly increased in the serum of active BD patients compared with inactive BD patients and controls. SNP analysis indicated an increased frequency of the OPN rs1126772 A allele in BD patients compared with controls. However, the significance was lost after Bonferroni correction. The prevalence of other SNPs of OPN and its receptors did not differ between BD patients and controls. The results suggest that an increased serum OPN level was associated with clinical severity of BD. There was no association of the tested SNPs of OPN and its receptors with BD in Chinese Han patients.

Serum galectin‐3 levels in patients with Behçet’s disease: association with disease activity over a long‐term follow‐up

There is a need for a laboratory marker that correlates with the clinical activity of Behçet's disease (BD). We aimed to investigate whether serum galectin-3 (Gal-3) levels were affected during the course of the disease with regard to disease activity. A total of 131 subjects were involved in the study as follows: Group 1: BD active (n = 39); Group 2: BD inactive (n = 31); Group 3: Disease controls with leucocytoclastic vasculitis confirmed with a skin biopsy (n = 22); and Group 4: Healthy control subjects (n = 39). The BD patients were followed regularly and samples were taken in their active and inactive periods of the disease over a 2-year period. Serum Gal-3 levels were significantly higher in active BD patients (mean 2.38) than inactive BD patients (mean 0.63; P < 0.0001) and the healthy control subjects (mean 0.75; P < 0.0001). There was no significant difference between the leucocytoclastic vasculitis and active BD patients (P = 0.093). Serum Gal-3 levels were positively correlated with clinical activity scores of active BD patients (r = 0.66, P < 0.0001). In addition, the Gal-3 levels were significantly higher in the active disease period when compared with the inactive period during the follow-up. There were no significant differences between the two inactive periods of the disease among the same patients. Further analyses revealed that patients with vascular involvement had significantly higher Gal-3 levels than the other active BD patients (mean 7.57; P = 0.007). The limitation of the study is the small number of patients with vascular involvement in the active BD patient group. Gal-3 levels are correlated with the activity of Behçet's disease especially with the vascular involvement.

Basic parameters of thrombophilia in ocular Behçet disease with posterior segment involvement

Aim:To assess basic thrombophilic parameters in both active and inactive periods of the ocular Behçet disease (BD) with posterior segment involvement in comparison with those in healthy adults as controls.Method:Thirty...

Expression of CXCR-1 and CXCR-2 chemokine receptors on synovial neutrophils in inflammatory arthritides: Does persistent or increasing expression of CXCR-2 contribute to the chronic inflammation or erosive changes?

ObjectiveTo analyze the CXCR-1 and CXCR-2 chemokine receptor expression on peripheral blood neutrophils (PBN) and synovial fluid neutrophils (SFN) of patients with rheumatoid arthritis (RA) and Behçet's disease (BD) (characterized by erosive and non-erosive arthritis, respectively), and to compare them with those of patients with osteoarthritis (OA). MethodsWe used flow cytometry to investigate the expression of CXCR-1 and CXCR-2 chemokine receptors on PBN and SFN of fifty-five (22 RA, 22 BD and 11 OA) age and sex-matched patients. ResultsIn respect to chemokine receptor expression on neutrophils isolated from patients with RA, mean fluorescein intensity (MFI) of CXCR-1 chemokine receptors on PBN from active and inactive RA patients, and SFN from patients with RA were 151 (90–395), 129 (81–539) and 136 (64–220), respectively, and there were not statistically significant difference each other. But MFI of CXCR-2 chemokine receptors on SFN of patients with RA was 18 (10–32), and significantly higher than PBN of active and inactive RA patients (MFI: 10 (6–15) and 12 (7–16), P=0.002 and 0.037, respectively). In respect to chemokine receptor expression on neutrophils isolated from patients with BD, MFI of CXCR-1 chemokine receptors on PBN of active BD patients was 245 (97–844), and higher than PBN of active RA patients and SFN of BD patients (MFI: 151 (90–395) and 134 (61–231), P=0.047 and 0.017, respectively). MFI of CXCR-2 chemokine receptors on PBN of active and inactive BD patients, and SFN of patients BD were 10 (6–14), 10 (2–16), and 12 (8–24), respectively, there were not statistically significant difference each other. MFI of CXCR-1 chemokine receptors on SFN from patients with RA, BD, and OA were 136 (64–220), 134 (61–231), and 114 (60–180), respectively, and there was no difference between the study groups. MFI of CXCR-2 chemokine receptors on SFN of patients with RA was 18 (10–32), and higher than patients with BD and OA (MFI: 12 (8–24) and 11 (9–18), P=0.037 and 0.005, respectively), though there was no difference between last two groups. ConclusionOur study points that CXCR-1 and CXCR-2 chemokine receptors of SFN may have diverse functions in the course of inflammatory arthritides. These results indicate that CXCR-2 chemokine receptor might play more critical role in long lasting accumulation of neutrophils within the synovial fluid of patients with RA.

Urinary 8-isoprostaglandin F 2α level in Behçet's disease

Although its etiology remains unknown, the increased production of reactive oxygen species in Behçet's disease (BD) have been reported. Furthermore, it has been suggested that vascular and endothelial tissue damage seen in BD is related to elevated reactive oxygen species generated by activated neutrophils from BD patients. To investigate the formation of lipid peroxidation in BD patients in vivo, urinary level of 8-isoprostaglandin F 2α was quantitated by enzyme immunoassay after solid phase extraction in different clinical forms of BD patients. There was no difference in urinary level of 8-isoprostaglandin F 2α between BD patient and healthy control group. There was also no difference in urinary levels of 8-isoprostaglandin F 2α in subgroup analyses of BD patients, i.e. in mucocutaneous and vascular type BD patients; active and inactive BD patients. Contrary to the findings in literature, we found no difference in urinary level of 8-isoprostaglandin F 2α between patients with systemic lupus erythematosus and healthy control group. These findings show no increase in lipid peroxidation despite the augmented formation of reactive oxygen species in BD patients. It may be interesting to assess formation of urinary level of 8-isoprostaglandin F 2α in BD patients who do not take any medication.

Adenosine deaminase enzyme levels, their relation with disease activity, and the effect of colchicine on adenosine deaminase levels in patients with Behçet’s disease

Behçet's disease (BD) is a systemic vasculitis. Although its clinical characteristics are well defined, the etiology and immune pathogenesis are not clear yet. Neutrophilic vasculitis, which is a consequence of immunological events, is suggested as the underlying pathophysiological mechanism. Adenosine deaminase (ADA) is a non-specific marker of T-lymphocyte activation. A total of 75 patients with BD (45 women and 30 men) and 25 age-matched and gender-matched healthy control volunteers (13 women and 12 men) were included in this study. BD patients were divided into three groups according to their clinical findings: inactive BD patients (group 1, n=25); active BD patients under colchicine treatment (group 2, n=25); and active BD patients without colchicine treatment (group 3, n=25). Plasma ADA (p-ADA) levels of all BD patients and the control group were measured and compared. The relationship between p-ADA levels and disease activity, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels was evaluated and correlated. Patients with BD had significantly higher p-ADA levels (20.6+/-6.3 U/l) than control subjects (12.8+/-1.8 U/l; P<0.001). The p-ADA levels of patients with active BD were significantly (for each, P<0.05) higher than those of inactive BD patients or controls. On the other hand, the difference was not significant (P>0.05) between active patients with or without colchicine use. In addition, there were significantly positive correlations between p-ADA, ESR and CRP levels in patients with BD (for each, P<0.05). However, disease duration or haemoglobin levels were not relevant. ADA level may be a valuable and supportive indicator of disease activity and is not affected by colchicine therapy in BD.