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Behect's disease is a chronic vasculitis characterized by complex multi-organ immune aberrations. However, a comprehensive understanding of the gene-regulatory profile of peripheral autoimmunity and the diverse immune responses across distinct cell types in Behcet's disease (BD) is still lacking. Here, we present a multi-omic single-cell study of 424,817 cells in BD patients and non-BD individuals. This study maps chromatin accessibility and gene expression in the same biological samples, unraveling vast cellular heterogeneity. We identify widespread cell-type-specific, disease-associated active and pro-inflammatory immunity in both transcript and epigenomic aspects. Notably, integrative multi-omic analysis reveals putative TF regulators that might contribute to chromatin accessibility and gene expression in BD. Moreover, we predicted gene-regulatory networks within nominated TF activators, including AP-1, NF-kB, and ETS transcript factor families, which may regulate cellular interaction and govern inflammation. Our study illustrates the epigenetic and transcriptional landscape in BD peripheral blood and expands understanding of potential epigenomic immunopathology in this disease. Integrated single-cell RNA-seq and ATAC-seq analysis of peripheral blood samples from Behcet's disease patients or healthy controls expands our understanding of potential epigenomic immunopathology in this disease. [ABSTRACT FROM AUTHOR]

Behçet Disease is a relapsing and remitting variable vessel vasculitis characterized by recurrent mucocutaneous ulcers that can involve almost every organ system in the body. Indeed, the presence of recurrent oral or genital ulcers with other auto-inflammatory symptoms should raise suspicion for this elusive disease. It is unique among the vasculitides in that it can affect vessels of small, medium, and large size and tends to involve venous rather than arterial circulation, and its effects on the pulmonary venous circulation are particularly notable for their role in disease mortality. Classically seen in Mediterranean, Middle-Eastern, and eastern Asian countries, and relatively rare in the United States, prevalence has been increasing, prompting an increased need for internists to be aware of Behcet's clinical presentation and treatment. As early recognition and diagnosis of the disease is key to successful treatment and better prognosis, this review provides a brief summary of the current etiological theories, important clinical manifestations, and treatments including newer biologic alternatives. [ABSTRACT FROM AUTHOR]

Pathergy reaction is the phenomenon of formation of non-healing skin lesions or ulcers following minor injuries. Although conceptually similar to the isomorphic reaction (Koebnerisation), these are two separate phenomena that should be distinguishable to treating clinicians. The underlying pathomechanisms of pathergy are not yet fully understood and subsequently therapy is lacking. Recent advances in the understanding of wound healing through keratinocyte and fibroblast cross-talk and mesenchymal stem cell (MSC) may hopefully foster the development of novel targeted therapies for pathergy-associated wounds and diseases in the near future. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells, the large granular lymphocytes differentiated from the common lymphoid progenitors, were discovered in early 1970's. They are members of innate immunity and were initially defined by their strong cytotoxicity against virus-infected cells and by their important effector functions in anti-tumoral immune responses. Nowadays, NK cells are classified among the recently discovered innate lymphoid cell subsets and have capacity to influence both innate and adaptive immune responses. Therefore, they can be considered as innate immune cells that stands between the innate and adaptive arms of immunity. NK cells don't express T or B cell receptors and are recognized by absence of CD3. There are two major subgroups of NK cells according to their differential expression of CD16 and CD56. While CD16+CD56dim subset is best-known by their cytotoxic functions, CD16-CD56bright NK cell subset produces a bunch of cytokines comparable to CD4+ T helper cell subsets. Another subset of NK cells with production of interleukin (IL)-10 was named as NK regulatory cells, which has suppressive properties and could take part in immune-regulatory responses. Activation of NK cells is determined by a delicate balance of cell-surface receptors that have either activating or inhibitory properties. On the other hand, a variety of cytokines including IL-2, IL-12, IL-15, and IL-18 influence NK cell activity. NK-derived cytokines and their cytotoxic functions through induction of apoptosis take part in regulation of the immune responses and could contribute to the pathogenesis of many immune mediated diseases including ankylosing spondylitis, Behçet's disease, multiple sclerosis, rheumatoid arthritis, psoriasis, systemic lupus erythematosus and type-1 diabetes. Dysregulation of NK cells in autoimmune disorders may occur through multiple mechanisms. Thanks to the rapid developments in biotechnology, progressive research in immunology enables better characterization of cells and their delicate roles in the complex network of immunity. As NK cells stand in between innate and adaptive arms of immunity and "bridge" them, their contribution in inflammation and immune regulation deserves intense investigations. Better understanding of NK-cell biology and their contribution in both exacerbation and regulation of inflammatory disorders is a requisite for possible utilization of these multi-faceted cells in novel therapeutic interventions. [ABSTRACT FROM AUTHOR]

Résumé: La maladie de Behçet est une vascularite systémique avec un grand polymorphisme clinique. L'atteinte vasculaire est souvent grave et peut engager le pronostic vital. Les artères et les veines de tout calibre peuvent être touchées. L'atteinte des vaisseaux digestifs est souvent grave. Nous rapportons le cas d'un jeune patient, de sexe masculin, dont la maladie de Behçet a été révélée par une ischémie digestive secondaire à une thrombose de la veine mésentérique supérieure étendue à la veine porte. Behçet's disease is a systemic vasculitis with a large clinical polymorphism. Vascular involvement is often severe and can be life-threatening. Arteries and veins of any size can be affected. The involvement of the digestive vessels is often severe. We report a case of a patient whose Behçet's disease was revealed by digestive ischemia secondary to superior mesenteric vein thrombosis extended to the portal vein. [ABSTRACT FROM AUTHOR]

Background: Polymorphisms in the interleukin-10 (IL-10) gene have been studied in various ethnic groups for possible association with Behçet's disease (BD). This study aimed to perform a meta-analysis of eligible studies to calculate the association of IL-10 polymorphisms with BD. A systematic literature search was carried out in PubMed, Embase, Web of Science, and Scopus databases to identify relevant publications, and extracted the respective results. Pooled odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the power of association with a random-effects model. Results: A total of 19 articles, consisting of 10,626 patients and 13,592 controls were included in the meta-analysis. The meta-analysis revealed significant associations in allelic and genotypic test models of − 819 (C vs. T: OR = 0.691, P < 0.001; CC vs. TT: OR = 0.466, P < 0.001; CC + CT vs. TT: OR = 0.692, P < 0.001; and CC vs. CT + TT: OR = 0.557, P < 0.001), − 592 (C vs. A: OR = 0.779, P = 0.002; CC + AA vs. AA: OR = 0.713, P = 0.021; and CA vs. AA: OR = 0.716, P = 0.016), rs1518111 (G vs. A: OR = 0.738, P < 0.001; GG vs. AA: OR = 0.570, P < 0.001; GG + AG vs. AA: OR = 0.697, P < 0.001; GG vs. GA + AA: OR = 0.701, P < 0.001; and AG vs. GG: OR = 0.786, P = 0.004) and rs1554286 (C vs. T: OR = 0.582, P < 0.001; CC vs. TT: OR = 0.508, P < 0.001; CC + CT vs. TT: OR = 0.605, P < 0.001; CC vs. CT + TT: OR = 0.665, P = 0.012; and CT vs. TT: OR = 0.646, P = 0.001). However, we failed to find any association between − 1082 polymorphism and susceptibility of BD. Conclusion: This meta-analysis demonstrated that the interleukin-10 -819, − 596, rs1518111 and rs1554286 polymorphisms could be responsible against BD susceptibility, and should probably be regarded as a protective factor for Behçet's disease. [ABSTRACT FROM AUTHOR]

Background: Behcet's disease (BD) is multi-systemic vasculitis, which generally is repeated oral and genital ulcerations as well as ocular and skin lesions. Today, the pathogenesis of BD remains mostly unknown. It is also suggested that the disease is probably related to autoinflammatory and autoimmune disorders, and innate immunity damages were perceived as key in its pathologic process. Only 5% of BD patients have neurological involvement, and it usually occurs in 4–6 years after the initial symptoms. Early onset of neurological impairment makes it difficult to diagnose and treat definitely. Case Presentation: A 38-year-old man was admitted to our hospital with numbness and weakness of the left extremities. Diffusion magnetic resonance imaging (MRI) revealed focal infarction in the posterior limb of the internal capsule. Skin pathology suggested small vessel vasculitis, and high-resolution MRI revealed intracranial arteritis. The patient had a negative skin pathery test and then developed a scar at the venous puncture site at the early stage of disease. Laboratory examination showed that interleukin 8 (IL-8) increased. The patient was treated with an immunosuppressive agent including mycophenolate mofetil, hydroxychloroquine, and colchicine. All symptoms were alleviated after half a year's treatment. There was neither stroke nor recurrence of oral ulcer thereafter. Conclusion: This case demonstrates that neurological involvement might be an early symptom of BD. IL-8 could act as a novel target for the treatment of BD theoretically and probably play a key role in disease recovery. [ABSTRACT FROM AUTHOR]

Behçet's disease (BD) is a chronic and rare multisystemic disorder defined by autoimmunity and inflammatory characteristics, manifested by ocular lesions, recurrent genital and oral ulcers, skin symptoms and arthritis as well as neurological, intestinal, and vascular involvement. Despite the unknown cause of BD, there is some strong documentation for immunological, genetic, environmental, and infectious factors playing a role in the pathogenesis of BD. While the nature of the genetic variants remains unidentified, many genetic risk factors are considered to contribute to BD susceptibility. Along with human leukocyte antigen gene encoding B*51 (HLA‐B*51) and areas including the major histocompatibility complex class I, genome‐wide association studies have recognized numerous other BD susceptibility genes including those encoding interleukin (IL)‐10, IL‐12 receptor β 2 (IL‐12RB2), IL‐23 receptor (IL‐23R), C‐C chemokine receptor 1 gene, signal transducer and activator of transcription 4 (STAT4), endoplasmic reticulum aminopeptidase (ERAP1), and genes encoding killer cell lectin‐like receptor family members (KLRC4‐KLRK1). It is believed that BD could be considered as a disorder lying in between autoimmune and autoinflammatory syndromes. The positive responses to classical immunosuppressive agents like azathioprine and cyclosporine and involvement of autoantigens in the initiation of the disorder are the main BD features that reflect the autoimmune nature of the disorder. In this review, we address recent findings on the role of common cytokines, antibodies and immunogenetic factors in BD. [ABSTRACT FROM AUTHOR]

Behçet's disease (BD) is a systemic inflammatory disease with a chronic, relapsing-remitting course of unknown etiology hallmarked predominantly by mucocutaneous lesions and ocular involvement. BD shares some common features with autoimmune and autoinflammatory diseases and spondyloarthropathies (MHC-I-opathies). It is related to more than one pathogenic pathway triggered by environmental factors such as infectious agents in genetically predisposed subjects. The interplay between genetic background and immune system is linked to the BD presentation. Genetic factors have been investigated extensively, and several recent genome-wide association studies have confirmed HLA-B * 51 to be the strongest genetic susceptibility factor. However, new non-HLA susceptibility genes have been identified. Genetic variations in the genes encoding the cytokines could affect their function and be associated with disease susceptibility. Infectious agents such as Streptococcus sanguinis or the differences in salivary or gut microbiome composition can be considered to trigger the innate-derived inflammation, which is, subsequently, sustained by adaptive immune responses. Altered trimming of microbial and/or endogenous peptides by endoplasmic reticulum aminopeptidase 1 (ERAP1), presented by HLA-B * 51 , may play a key role in BD pathogenesis causing an alteration in T cell balance with downregulation of Tregs and expansion of Th1 and Th17. The activity of neutrophils is increased and there is an intense neutrophil infiltration in the early stage of inflammation in organs affected by the disease. Association with HLA-B * 51 and increased IL-17 response seems to have an important role in neutrophil activity. In this paper, we provide an overview of the most recent advances on BD etiopathogenesis. [ABSTRACT FROM AUTHOR]

Background and aims: Behçet’s disease (BD) is a chronic multisystemic inflammatory disease with complex etiopathogenesis. Th1-proinflammatory cytokines seem to be involved in its pathogenesis. Our current study aims to evaluate interleukin-18 (IL-18) and nitric oxide (NO) involvement in the development of different clinical manifestations of BD as well as to investigate the corticosteroid therapy effect on this production in Algerian patients.Methods: For this purpose, we evaluated in vivo and ex vivo IL-18, interferon-γ (IFN-γ) levels using ELISA and NO production by the Griess’ method in naïve-active and corticosteroid-treated BD patients with different clinical manifestations. Additionally, we assessed CD40/CD40L expression by flow cytometrics assay in these groups of patients.Results and discussion: Our results indicate that IL-18 and nitrite levels were higher in naïve-active BD patients. Interestingly, this high production differed according to the clinical manifestations and was associated with an increased risk of mucocutaneous and vascular involvement. Concerning corticosteroid treated-active BD patients, no difference was observed in this production between each clinical subgroup. However, IFN-γ levels increased in all categories of active patients. Interestingly, corticosteroid therapy reduced significantly these inflammatory mediators regardless of the clinical manifestations studied. In addition, the CD40/CD40L expression differed according to the clinical presentations.Conclusion: Collectively, our results suggest that concomitant high production of IL-18 and NO in naïve-active BD patients is related to an increased risk of mucocutaneous lesions and vascular involvement. Moreover, the relationship between these two inflammatory markers could constitute a predictable tool of BD clinical presentations and an early factor of therapy efficiency. [ABSTRACT FROM AUTHOR]

Behçet’s disease (BD) is a chronic inflammatory disease characterized by recurrent mucocutaneous, ocular, and skin lesions. Immunosenescence is associated with increased susceptibility to infection and chronic low grade inflammation. This study aimed to investigate the differences in the frequencies of immunosenescent cells in the peripheral blood mononuclear cells (PBMCs) of patients with BD. PBMCs were isolated from age-matched patients with active BD (n = 19), inactive BD (n = 20), disease controls (DCs, n = 15) and healthy controls (HCs, n = 15). The frequencies of senescent CD4+ T cells (CD3+ CD4+ CD27− CD28− cells), CD8+ T cells (CD3+ CD8+ CD27− CD28− cells) and B cells (CD19+ CD27− IgD− cells) were analyzed using flow cytometry. Senescence-associated β galactosidase activity was also measured in CD8+ T cells using flow cytometry with 5-dodecanoylaminofluorescein di-β-d-galactopyranoside. Frequencies of senescent CD4+ and CD19+ cells were not significantly different between the groups. The frequency of senescent CD8+ T cells was significantly higher in active BD than in DCs and HCs. C-reactive protein and erythrocyte sedimentation rate levels, which indicate disease activity, did not correlate with increased frequencies of immunosenescent cells. Steroid treatment, specific organ involvement, and HLA-B51 status did not have a significant influence on the frequencies of immunosenescent cells. Frequencies of senescence-associated β galactosidase+ CD8+ T cells were significantly higher in active BD and inactive BD compared to DCs and HCs. There was an increased frequency of senescent CD8+ T cells in the PBMCs of patients with BD. [ABSTRACT FROM AUTHOR]

The association between carriage of the human leucocyte antigen (HLA)-B*51 allele and development of Behçet's disease (BD) has been known since the early 1970s, but the exact mechanisms responsible for its role in pathogenesis remain much-debated. In an effort to explain the disease process, it has been suggested that BD constitutes one of a newly termed group of diseases, the 'MHC-I-opathies'. Other MHC-I-opathies include ankylosing spondylitis and HLA-B*27-associated spondyloarthropathies and HLA-C*0602-associated skin psoriasis. Recent work analysing the peptidome of HLA-B*51 suggests that altered peptide presentation by HLA-B*51 is vital to the disease process. In this review, we argue that immune receptor interactions with HLA-B*51 or the HLA-B*51-peptide complex could lead to development of inflammation in BD. The evidence for CD8+ T cell involvement is weak, and based on emerging studies it seems more likely that natural killer (NK) or other cell interactions, perhaps mediated by leucocyte immunoglobulin-like receptor (LILR) or killer immunoglobulin-like receptor (KIR) receptors, are culpable in pathogenesis. HLA misfolding leading directly to inflammation is another hypothesis for BD pathogenesis that deserves greater investigation. Ultimately, greater understanding of HLA-B*51's unique role in BD will probably lead to improved development of therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective: Overwhelming inflammatory chemokines and cytokines characterize the immunological profile and inflammatory settings of Behcet disease (BD). The connection between autophagy-related genes (ATGs) and various perspectives of innate and adaptive immunobiology such as antigen presentation, immune tolerance, lymphocyte development and differentiation, cytokine signaling, and inflammation have been implicated. The aim of this study was to evaluate the mRNA expression profile of ATGs in macrophages of patients with BD. Materials and Methods: Whole blood samples were obtained from 10 BD patients and 10 healthy controls. Monocytes were isolated from the blood samples and then differentiated to macrophages using macrophage colony-stimulating factor (M-CSF). After total RNA extraction and cDNA synthesis, quantitative analysis of ATGs including ATG5, ATG7, ATG12, LC3b, mTOR, RAPTOR, and RICTOR was conducted by SYBR Green master mix and real-time polymerase chain reaction (PCR). Results: mRNA expression of all ATGs was downregulated in macrophages of BD patients compared with healthy controls. It is worth to note that the downregulation of ATG12 and LC3b mRNAs in macrophages of BD patients was statistically significant in comparison to that of healthy control group (P = 0.007 and 0.021, respectively). Conclusion: Considering the role of autophagy in initiation of immune responses and then clearance of dead cells as well as its participation in the development and differentiation of immune cells, downregulation of ATGs in macrophages of BD patients may be involved in uncontrolled immune response and overproduction of inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Behçet’s disease (BD) is a chronic autoimmune condition primarily prevalent in populations along the Mediterranean Sea. The exact etiology of BD has not been fully explained yet, but the disease occurrence is associated with a genetic factor, human leukocyte antigen (HLA)-B51 antigen. Among the various immunodysfunctions that are found in BD, patients are increased neutrophil motility and superoxide production, as well as elevated production of tumor necrosis factor (TNF)-α and decreased production of interleukin (IL)-10. Elevated levels of inflammatory cytokines like IL-1 and IL-17 in BD have been found associated with aberrant expression of microRNA. Gene polymorphisms in BD patients have been observed in molecules involved in responses to pathogens that can ultimately modulate the host antimicrobial response. Moreover, several single nucleotide polymorphisms (SNPs) have been reported in genes encoding chemokines and adhesion molecules; many of these changes manifest as increases in vascular inflammation and vascular damage. Lastly, genetic and epigenetic changes have been suggested as involved in the pathogenesis of BD. Modifications in DNA methylation have been found in BD patient monocytes and lymphocytes, leading to adverse function of these cells. This review presents a comprehensive compilation of the literature with regard to the immunodysfunction underlying BD, as well as of the genetics, newly described clinical specifications and novel treatment strategies using immunomodulants based on the current understanding of BD. [ABSTRACT FROM PUBLISHER]

Behçet’s disease (BD) is an inflammatory multisystemic disorder associated with orogenital ulcers, uveitis and skin lesions with unpredictable episodes of exacerbations and remissions. Even though several immunological and environmental factors contribute to BD progression, its ethiopathogenesis remains uncertain and elusive. Considered as one of the potent environmental factors that can increase prevalence of some autoimmune and inflammatory disorders, vitamin D deficiency has been linked to several diseases as BD. The aim of this study is to assess vitamin D status in Algerian BD patients and its relationship with disease activity. Immunomodulatory effect of this vitamin on nitric oxide (NO), inflammatory mediator, was also undertaken. Serum 25(OH) vitamin D levels were measured in healthy controls (HC), active and inactive BD patients with an electrochemiluminescence method. After treatment of HCs’ and patients’ peripheral blood mononuclear cells with different concentrations of vitamin D3, NO production was evaluated with Griess method, while inducible nitric oxide synthase (iNOS) and NF-κB expression with immunofluorescence test. A high decrease of vitamin D levels was noted in active BD patients compared to those of inactive stage and HC. However, a higher NO production was observed during active stage of BD compared to inactive one. In inactive BD, vitamin D levels correlates negatively with NO. Interestingly, vitamin D3 inhibitsex vivoNO production, iNOS and NF-κB expression in BD patients. In conclusion, vitamin D deficiency was associated with active BD. This vitamin down-modulates NO production in BD patients, suggesting that it may be considered as promising therapy modulating inflammation during BD. [ABSTRACT FROM AUTHOR]

Aim To explain the missing heritability after the genome-wide association studies era, sequencing studies allow the identification of low-frequency variants with a stronger effect on disease risk. Common variants in the interleukin 10 gene ( IL10) have been consistently associated with Behçet's disease ( BD) and the goal of this study is to investigate the role of low-frequency IL10 variants in BD susceptibility. Methods To identify IL10 low-frequency variants, a discovery group of 50 Portuguese BD patients were Sanger-sequenced in a 7.7 kb genomic region encompassing the complete IL10 gene, 0.9 kb upstream and 2 kb downstream, and two conserved regions in the putative promoter. To assess if the novel variants are BD- and/or Portuguese-specific, they were assayed in an additional group of BD patients (26 Portuguese and 964 Iranian) and controls (104 Portuguese and 823 Iranian). Results Rare IL10 coding variants were not detected in BD patients, but we identified 28 known single nucleotide polymorphisms with minor allele frequencies ranging from 0.010 to 0.390, and five novel non-coding variants in five heterozygous cases. ss836185595, located in the IL10 3′ untranslated region, was also detected in one Iranian control individual and therefore is not specific to BD. The remaining novel IL10 variants (ss836185596 and ss836185602 in intron 3, ss836185598 and ss836185604 in the putative promoter region) were not found in the replication dataset. Conclusion This study highlights the importance of screening the whole gene and regulatory regions when searching for novel variants associated with complex diseases, and the need to develop bioinformatics tools to predict the functional impact of non-coding variants and statistical tests which incorporate these predictions. [ABSTRACT FROM AUTHOR]

Background: Behçet’s disease (BD) is a rare, chronic autoinflammatory disorder of unknown origin. Natural killer (NK) cells are one of the major immunoregulatory cell groups of the innate immune system, but their role in BD pathogenesis is not well documented. Objectives: We aimed to investigate the role of NK cell subsets and their cytokine secretion and cytotoxic activity in patients with BD. Patients and methods: The study group consisted of BD patients who had only mucocutaneous involvement, and they were compared with healthy subjects. BD patients were divided into two groups according to their frequencies of oral ulcerations. NK cell cytotoxicity was determined using CD107a expression and a CFSE-based cytotoxicity test. Expression of NK cell receptors and surface markers and the intracellular IL-5, IL-10, IL-17, and IFN-γ levels in CD16+NK cells were assessed by flow cytometry. Results: Although the cytokine secretion pattern was different, no difference was obtained in cytotoxic activity, expression of activatory receptors, or degranulation of NK cells. Conclusion: Increases in NK1/NK2 ratio and CD16+IFN-γ+NK1 cells might support the idea of a biased IFN-γ dominant immune response in the mucocutaneous involvement of BD pathogenesis. Although the cytokine secretion pattern was different, no difference was obtained in cytotoxic activity, expression of activatory receptors, or degranulation of NK cells. [ABSTRACT FROM AUTHOR]

Objective: The immune classification of Behçet'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 Behçet'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-a) (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. [ABSTRACT FROM AUTHOR]

We have reported that helper T type 17 (Th17) cells increased in patients with Behcet's disease (BD). It remains obscure how Th17 cells increase in the patients. We here analyzed whether T cells preferentially differentiate into Th17 cells in response to various inflammatory cytokines in patients with BD. Exogenous interleukin (IL)23 sustained the higher Th17 cell frequencies of CD4+CD45RO+ T cells after a 2-day culture in vitro in patients with BD, whereas the T cell subpopulation of normal individuals did not respond to IL23 to sustain/increase Th17 cell frequencies. IL23 receptor positive cell frequencies in freshly isolated BD CD4+CD45RO+ T cells correlated with Th17 cell frequencies assessed by intracellular cytokine staining. After a 2-day culture with IL23, BD CD4+ T cells retained the correlation between IL23 receptor expression level and extent of IL17 secretion (as indicated by Th17 cell frequencies), whereas such correlation was not noted in normal individuals. IL23 signals with its receptor were thus suggested to induce IL17 secretion (Th17 cell frequencies) in a short-time culture in patients with BD. We cultured CD4+CD45RO− T cells for 11 days with various inflammatory cytokines to study which cytokine associated with the enhanced Th17 frequencies in the patients. IL17 production by CD4+CD45RO− T cells of BD patients increased significantly by the supplementation of IL1β and tumor necrosis factor (TNF)α, in addition to IL23, compared with that of normal individuals. These results suggest that proinflammatory cytokines, such as IL1β, TNFα, and IL23, may associate with the expansion of Th17 cells in patients with BD. This study was registered with the University Hospital Medical Information Network-Clinical Trials Registry (UMIN000003806). [ABSTRACT FROM AUTHOR]

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Behçet's disease (BD) is a complex, multisystemic inflammatory disorder of unclear etiology. Single nucleotide polymorphisms in tumor necrosis factor (TNF) and interleukin (IL)-10 genes have been implicated in susceptibility to BD with inconsistent results in several ethnic populations. The aim of this case-control study was to evaluate the association of TNF-α (-308G/A), TNF-β (+252A/G), and IL-10 (-1082G/A, -819C/T, and -592 C/A) polymorphisms with susceptibility of BD in Saudi patients. Molecular genotyping of TNF-α, TNF-β, and IL-10 gene polymorphisms was performed to analyze the alleles and genotypes distribution in 272 Saudi subjects, including BD patients (61) and healthy controls (211). The frequencies of allele A and genotype GA of TNF-α (-308G/A) were significantly higher, whereas those of allele G and genotypes GG were significantly lower in BD patients than controls, indicating that A allele and GA genotype are susceptible, while G allele and GG genotype may be refractory to BD. The distribution of frequencies of alleles and genotype of TNF-β (+252A/G) promoter polymorphism was not significantly different between BD patients and healthy controls. Genotypes 1082GG, -819TT, and 592AA of IL-10 polymorphisms are significantly associated with susceptibility risk of BD, while genotypes 1082AA, 1082GA, 819CC, 819CT, 592CC, and 592CA are resistant to BD. This study indicates that TNF-α (-308G/A) and IL-10 (-1082G/A, -819C/T, and -592C/A) polymorphisms are associated with risk of BD susceptibility in Saudi patients. However, larger scale studies in Saudi population as well as in other ethnicities are needed to confirm this association. [ABSTRACT FROM AUTHOR]

Behçet's disease (BD) is a multisystem inflammatory disorder. Intracardiac thrombus formation (ICTF) is an uncommon but important complication of BD. To highlight recent insights into this disease, we aimed to review ICTF and other systemic involvements associated with ICTF in BD. We conducted a comprehensive review of the relevant literature in MEDLINE and EMBASE from 1966 to 2014 to analyze cumulated data about ICTF in BD. We aimed to evaluate 93 cases of BD with ICT (group 1), four of which have been recently identified and have not been discussed in the relevant literature yet, and to compare the frequency of pulmonary, venous and arterial involvements in group 1 and general Behçet population (group 2). The right heart was the most common site of ICTF in group 1. Pulmonary involvement, venous involvement (especially venous thrombosis) and arterial involvement were more frequent in group 1 than in group 2 (56 vs. 0.7 %, 42 vs. 10 % and 38 vs. 0.8 %, respectively, p < 0.0001). The diagnosis of BD should be considered if a patient presents with a mass in the right-sided cardiac chambers, even in the absence of the characteristic clinical manifestations of the illness. This approach is particularly applicable if the patient is a young man from the Mediterranean basin or the Middle East. All Behçet patients with ICTF must be investigated with thoracic computed tomography for pulmonary and arterial involvements and lower extremity venous Doppler ultrasonography for venous thrombosis, regardless of whether they are symptomatic for these systems. [ABSTRACT FROM AUTHOR]

Behçet's disease (BD) is a chronic inflammatory disease. Increased productions of cytokines including interleukin (IL)-1β and IL-18 are documented, and IL-1α and β gene polymorphisms are associated with susceptibility to the disease. IL-33 is a recently discovered member of IL-1 cytokine family. The aim of the study was to detect serum IL-33 level and IL-33 gene polymorphisms in a cohort of BD. Unrelated 117 patients with BD and 149 healthy controls (HC) were enrolled. Serum IL-33 levels were analyzed by enzyme-linked immunosorbent assay method. DNA samples were harvested using an appropriate commercial DNA isolation kit. Four single nucleotide polymorphisms of IL-33 gene (rs7044343, rs1157505, rs11792633 and rs1929992) were genotyped using the appropriate commercial primer/probe sets on real- time PCR. Serum IL-33 level was not significantly different in the BD and HC groups ( p > 0.05). However, its level was lower in the active BD patients compared to the inactive ones and HC group ( p = 0.044 and p = 0.037, respectively). There was no significant difference in terms of the genotypic and allelic distributions of rs1157505 and rs1929992 polymorphisms ( p > 0.05 for all). However, the TT variants of rs7044343 and rs11792633 polymorphisms were very rare, and the T allele frequencies of these polymorphisms were lower, in the BD group compared to the HC group ( p < 0.0001 for all). The rs7044343 and rs11792633 variants of IL-33 gene are associated with the decreased risk of BD in our cohort. Therefore, it may be concluded that IL-33 acts a protective role on the pathogenesis of BD. [ABSTRACT FROM AUTHOR]

To assess the association between polymorphisms of the IL-6 -174 G/C and Behçet's disease (BD) in Tunisian patients. DNA was extracted from blood samples taken from 43 Tunisian patients and 43 healthy controls. The polymorphisms were analyzed by PCR with the PCR-RFLP. No significant association was found between patients and controls concerning polymorphism of IL6 -174 G/C between the (allelic frequency: C (17.44 vs 8, 13%; P=0.17) et G (82,55 vs 91,86%; P= 0.21). Neither age of onset of BD nor sex appears to be influenced by allelic variation of SNP-174 G / C of IL6. Disease duration of BD was longer in patients having the form 174 G-allele. SNP -174G/C was more frequent in patients without significant association (32.5 vs 16,26% ; P=0.07). SNP -174 G/C was not associated with the HLA B51. Neither age of onset of BD nor sex appears to be influenced by SNP-174 G / C of IL6. Disease duration of BD was longer in the absence of the SNP-174 G/C IL6, with no significant difference (79.2 + / -45.095 vs.70.28 + / - 47.034 months, P=0.59). The polymorphism of IL6 -174 G/C does not modulate clinical expression of BD. The single nucleotide polymorphisms of the IL-6 do not appear to be associated with BD reconstruction. [ABSTRACT FROM AUTHOR]

Lesions of Behçet's disease (BD) show vascular infiltrates of immune cells expressing integrins. β2 integrins (CD11/CD18) play a major role in cell migration to the inflammatory lesion and also induce cytokine production. Thus, genetic polymorphisms of CD11/CD18 may be associated with the pathogenesis of BD. In this study, nine single nucleotide polymorphisms (SNPs) of the CD11a, CD11c, and CD18 were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and haplotype analysis in 305 BD patients and 266 healthy controls. The frequencies of genotype rs11574944 CC and haplotype rs11574944C-rs2230433G-rs8058823A in CD11a were significantly lower in BD patients. The frequencies of genotype rs2230429 CC, rs2929 GG, and haplotype rs2230429C-rs2929G in CD11c were higher in BD patients. The frequencies of genotype rs235326CC and haplotype rs2070946A-rs235326C-rs760456G-rs684G in CD18 were significantly higher in the BD patients than in the controls. Other SNPs in CD11a, CD11c, and CD18 gene were not significantly different. Therefore, the major genotype and haplotype of CD11a/CD18 may play a role in decreasing the susceptibility of BD, whereas the major genotype and haplotype of CD11c/CD18 may play a role in increasing the susceptibility of BD. [ABSTRACT FROM AUTHOR]

Objective. Behçet's disease (BD) is a systemic inflammatory disease with unknown etiology. Studies have shown that some T helper (Th) 1-associated cytokines have role in the inflammation of BD. The CD4+ Th cells can be differentiated into Th1, Th2, Th17 and Th22 secrete different cytokines to regulate immune system. In this study, cytokine secretion of Th subsets in BD was investigated. Methods. The study group consisted of 26 BD patients with mucocutaneous involvement and 12 healthy subjects. Lymphocyte subpopulations, IL-5, IL-10, IL-17, IL-22 and IFN-γ secretion of CD4+ T and Foxp3+ Treg cells were determined by flow cytometry. Results. Compared with healthy subjects, Th1 (IL-17A−IL-22−IFN-γ+), Th22 (IL-17A−IL-22+IFN-γ) and IL-17A+IFN-γ+-secreting cells were significantly increased, and the percentage of Treg cells were dramatically reduced in BD patients. The frequency of recurrent oral ulcers was associated with increased Th22 cells. Conclusions. Our study describes an association between Th22 cell subset and IL-17A+ IFNγ+-secreting cells with mucocutaneous BD. These findings revealed that reduced levels of Tregs and increased levels of Th1 and Th22 cells as well as Th17/Th1 cells might be associated with the pathogenesis of BD. [ABSTRACT FROM AUTHOR]

Background Behçet's disease (BD) is a recurrent multisystemic inflammatory disease characterized by recurrent oral aphthous and genital ulcers, ocular lesions and cutaneous lesions. Although many studies of cytokine levels in sera of BD patients have been conducted, there are only limited number of studies about the cytokine expression and cellular infiltration in the BD-related skin lesions. Objectives To investigate the immunophenotypes and cytokine profiles of BD-related skin lesions. Methods Twenty patients who fulfilled the diagnostic criteria for BD with BD-related skin lesions were enrolled in this study. We assessed the histopathological features of BD-related skin lesions by immunohistochemical studies with anti-human CD4, CD8, CD68, FoxP3, CD-11b, IFN-γ and IL-4 antibodies. Results Immunophenotyping of inflammatory infiltrating cells showed that CD68+ macrophages were the most common type of infiltrated cells in erythema nodosum-like lesions, erythema multiforme-like lesions and Sweet's syndrome-like lesions, whereas neutrophils were the main population of inflammatory infiltrating cells in papulopustular lesions. In all of the four types of BD-related skin lesions, the percentage of CD8+ T cells was higher than that of CD4+ T cells ( P < 0.05), and IL-4 expression was stronger than IFN-γ expression ( P < 0.05). Conclusion In this study, we assessed the infiltrating inflammatory cells and cytokine expression of acute cutaneous lesions in BD through immunohistochemical staining of BD-related skin lesions. Further studies about the disease activity and the molecular biology underlying the cutaneous inflammation are needed to understand the detailed pathogenesis of BD. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the predisposition of common pre-miRNA SNPs with Behcet’s disease (BD), Vogt–Koyanagi–Harada (VKH) syndrome and acute anterior uveitis (AAU) associated with ankylosing spondylitis (AS). A two-stage association study was carried out in 859 BD, 400 VKH syndrome, 209 AAU +AS + patients and 1,685 controls all belonging to a Chinese Han population. Genotyping, the expression of miR-196a and Bach1 (the target gene of miR-196a), cell proliferation, cytokine production were examined by PCR–RFLP, real-time PCR, CCK8 and ELISA. In the first stage study, the results showed significantly increased frequencies of the miR-196a2/rs11614913 TT genotype and T allele in BD patients (adjusted Pc = 0.024, OR = 1.63; adjusted Pc = 5.4 × 10 −3, OR = 1.45, respectively). However, no significant association of the tested SNPs with VKH and AAU +AS + patients was observed. The second stage and combined studies confirmed the association of rs11614913 with BD (TT genotype: adjusted Pc = 6×10 −5, OR = 1.53; T allele: adjusted Pc = 8×10 −6, OR = 1.35; CC genotype: adjusted Pc = 0.024, OR = 0.68). A stratified analysis showed an association of the rs11614913 TT genotype and T allele with the arthritis subgroup of BD ( Pc = 5.3 × 10 −3, OR = 1.89; Pc = 0.015, OR = 1.56, respectively). Functional experiments showed a decreased miR-196a expression, an increased Bach1 expression and an increased production of IL-1β and MCP-1 in TT cases compared to CC cases ( P = 0.023, P = 0.0073, P = 0.012, P = 0.002, respectively). This study shows that a functional variant of miR-196a2 confers risk for BD but not for VKH syndrome or AAU +AS + by modulating the miR-196a gene expression and by regulating pro-inflammatory IL-1β and MCP-1 production. [ABSTRACT FROM AUTHOR]

Objective: We have conducted the first study of the association of interleukin (IL)-10, tumor necrosis factor alpha (TNF-α) and IL23R-IL12RB2 regionSNPswith Behçet's disease (BD) in Western Algeria. Methods: A total of 51 BD patients and 96 unrelated controls from West region of Algeria were genotyped by direct sequencing for 11 SNPs including 2 SNPsfrom the IL10 promoter [c.-819T>C (rs1800871), c.-592A>C (rs1800872)], 6 SNPs from the TNF-α promoter [c.-1211T>C (rs1799964), c.-1043C>A (rs1800630), c.-1037C>T (rs1799724), c.-556G>A (rs1800750), c.-488G>A (rs1800629) and c.-418G>A (rs361525)], and 3 SNPs from the IL23R-IL12RB2 region [g.67747415A>C (rs12119179), g.67740092G>A (rs11209032) and g.67760140T>C (rs924080)]. Results: The minor alleles c.-819T and c.-592A were significantly associated with BD (OR= 2.18; 95% CI 1.28-3.73, p = 0.003); whereas, there was weaker association between TNF-αpromoter SNPs or IL23R-IL12RB2 region and disease risk. Conclusion: Unlike the TNF-αand the IL23R-IL12RB2 region SNPs, the two IL10 SNPs were strongly associated with BD. The -819T, and -592A alleles and the -819TT, -819CT, and -592AA and -592CA genotypes seem to be highly involved in the risk of developing of BD in the population of Western Algeria. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the possible role of angiogenin, vascular endothelial growth factor, (VEGF) and basic fibroblast growth factor (bFGF) in the pathogenesis of BD. Design and methods: Sixty-five patients with BD and 21 healthy control subjects were included in the study, and serum angiogenin, bFGF, and VEGF concentrations were measured by using in-vitro enzyme immunoassay (ELISA) kits according to the manufacturer's instructions. Results: The median serum angiogenin level was significantly higher in patients with BD (391.8; range:151.6-594.8 pg/ml) than controls (298.8; range:241.9-449.6 pg/ml) ( p = 0.001). The levels were similar in both ocular and non-ocular BD patients ( p = 0.537). The mean serum bFGF level was higher in patients with BD (38.8 ± 12.3 pg/ml) than controls (33.2 ± 11.3 pg/ml); the median serum VEGF level was also higher in BD patients (239.7; range:53-991.3 pg/ml) than controls (189.4; range:53.6-357.9 pg/ml). But these differences were not statistically significant. Serum bFGF and VEGF levels were also not different statistically in ocular and non-ocular Behçet's patients. There was no statistically significant relationship between serum angiogenin, bFGF, and VEGF levels and the presence of active eye disease or anatomic location of uveitis. While there was a correlation of borderline significance in angiogenin levels between the patients with anterior uveitis and panuveitis ( p = 0.053), we did not obtain any correlation between serum angiogenin, bFGF, and VEGF levels and the duration of BD. Conclusions: This study suggests that angiogenin may be associated with pathophysiology of BD, and highlights the need of further investigation of the role of angiogenin, bFGF, and VEGF serum levels in BD susceptibility and its clinical manifestations. [ABSTRACT FROM AUTHOR]

Objective Independent replication of the findings from genome-wide association studies (GWAS) remains the gold standard for results validation. Our aim was to test the association of Behçet's disease (BD) with the interleukin-10 gene ( IL10) and the IL-23 receptor-IL-12 receptor β2 ( IL23R- IL12RB2) locus, each of which has been previously identified as a risk factor for BD in 2 different GWAS. Methods Six haplotype-tagging single-nucleotide polymorphisms (SNPs) in IL10 and 42 in IL23R-IL12RB2 were genotyped in 973 Iranian patients with BD and 637 non-BD controls. Population stratification was assessed using a panel of 86 ancestry-informative markers. Results Subtle evidence of population stratification was found in our data set. In IL10, rs1518111 was nominally associated with BD before and after adjustment for population stratification (odds ratio [OR] for T allele 1.20, 95% confidence interval [95% CI] 1.02-1.40, unadjusted P [ Punadj] = 2.53 × 10−2; adjusted P [ Padj] = 1.43 × 10−2), and rs1554286 demonstrated a trend toward association ( Punadj = 6.14 × 10−2; Padj = 3.21 × 10−2). Six SNPs in IL23R-IL12RB2 were found to be associated with BD after Bonferroni correction for multiple testing, the most significant of which were rs17375018 (OR for G allele 1.51, 95% CI 1.27-1.78, Punadj = 1.93 × 10−6), rs7517847 (OR for T allele 1.48, 95% CI 1.26-1.74, Punadj = 1.23 × 10−6), and rs924080 (OR for T allele 1.29, 95% CI 1.20-1.39, P = 1.78 × 10−5). SNPs rs10489629, rs1343151, and rs1495965 were also significantly associated with BD in all tests performed. Results of meta-analyses of our data combined with data from other populations further confirmed the role of rs1518111, rs17375018, rs7517847, and rs924080 in the risk of BD, but no epistatic interactions between IL10 and IL23R-IL12RB2 were detected. Results of imputation analysis highlighted the importance of IL23R regulatory regions in the susceptibility to BD. Conclusion These findings independently confirm, extend, and refine the association of BD with IL10 and IL23R-IL12RB2. These associations warrant further validation and investigation in patients with BD, as they may have implications for the development of novel therapies (e.g., immunosuppressive therapy targeted at IL-23p19). [ABSTRACT FROM AUTHOR]

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J Oral Pathol Med (2012) 41: 73-79 Background: One of the factors involved in the pathogenesis of Behçet disease (BD) and recurrent aphthous ulcerations (RAU) is a cell-mediated immune response in which several cytokines (interleukin-2, interleukin-6) and T regulatory cell (T reg cell) population seem to play a major role. The aim of this study was to measured the interleukin-2 (IL-2), interleukin-6 (IL-6) levels and analysis of CD4+ CD25+ Foxp-3+ Treg cells in peripheral blood from patients with BD and RAU. In addition; we also analysed peripheral blood from healthy subjects for comparison. Methods: Thirty patients (15 men and 15 women) with BD, 30 patients (12 men and 18 women) with RAU and 15 healthy control subjects (nine men and six women) participated in the study. Analysis of CD4+ CD25+ Foxp-3+ Treg cells, IL-2 and IL-6 levels have been measured in flow cytometry. Results: No statistical differences were observed in the serum levels of IL-2 and IL-6 between BD and RAU patients, and healthy subjects. Although there were no statistical differences in the number of CD4+ CD25+ Foxp-3+ cells between groups, there were statistically significant differences in the number of CD4+ CD25bright Treg cells. CD4+ CD25bright Treg cells were significantly increased in BD and RAU patients compared to healthy subjects. Statistical analysis revealed no difference according to the number of CD4+ CD25bright cells between BD and RAU patients. Conclusions: These results indicate that CD4+ CD25bright T regulatory cells may be contributing factor in the pathogenesis of BD and RAU. [ABSTRACT FROM AUTHOR]

Behçet disease (BD) is a chronic, inflammatory, and multisystemic condition with an uncertain pathogenesis. One of the major immunologic findings in BD pathogenesis is increase in activity of neutrophil. An increase in the cytosolic free Ca²⁺[Ca²⁺](i) concentration that induces Ca²⁺ signaling is an important step that participates in the neutrophil activation and reactive oxygen species production that leads to tissue damage in body cells. We aimed to investigate the effects of colchicine on oxidative stress and Ca²⁺ release in serum and neutrophil of BD patients with active and inactive periods. Twelve Behçet patients (6 active and 6 inactive) and 6 control subject were included in the study. Disease activity was considered by clinical findings. Serum and neutrophil samples were obtained from the patients and control subjects. Neutrophils from patients with active BD were divided into three subgroups and were incubated with colchicine, verapamil + diltiazem, and colchicine + verapamil + diltiazem, respectively. Erythrocyte sedimentation rate, leucocytes counts, serum C-reactive protein, neutrophil, and serum lipid peroxidation and intracellular Ca²⁺ release levels were higher in active and inactive groups than in the control group, although their levels were lower in active group than in inactive group. However, neutrophil Ca²⁺ release levels were decreased in colchicine, verapamil + diltiazem, and colchicine + verapamil + diltiazem groups group compared to active group. Serum glutathione, vitamin A, vitamin E, and β-carotene concentrations were lower in active and inactive groups than in the control group, although serum vitamin E and β-carotene concentrations were higher in the inactive group than in the active group. Neutrophil and serum glutathione peroxidase activity within the three groups did not change. In conclusion, we observed the importance of Ca²⁺ influx into the neutrophils and oxidative stress in the pathogenesis and activation of the patients with BD. Colchicine induced protective effects on oxidative stress by modulating Ca²⁺ influx in BD patients. [ABSTRACT FROM AUTHOR]

Behçet's disease (BD) is a chronic inflammatory multisystem disorder which can involve the central nervous system (CNS). Cerebral venous thrombosis (CVT) is one of its major neurological manifestations. We aimed to review the epidemiologic and clinical features of CVT in patients with BD, as well as the available data on therapeutic interventions and prognosis. Systematic review of all observational studies of BD patients was done. Search strategy included electronic searches of MEDLINE (1966-August 2009). Occurrence of CVT in BD and Neuro-Behçet patients, occurrence of CVT as the inaugural manifestation of BD, clinical and neuro-imaging characteristics of CVT, prothrombotic evaluation, treatment options and prognosis were extracted. A meta-analysis of available results was performed when feasible. Twenty-three studies were included, with 290 cases of CVT in patients with BD. The incidence of CVT per 1,000 person-years was 3 (95% CI: 1-8), being higher in retrospective studies (3.2, 95% CI: 1-10) than in prospective studies (2.7, 95% CI: 1-13). Among patients with neurologic involvement, the incidence rate was 15.1/1,000 person-years. The onset was progressive in 77% of the patients. Intracranial hypertension syndrome was a frequent presentation of CVT in BD. The most frequent sites of occlusion were the superior sagittal and the transverse sinus. Most of the studies did not evaluate the prevalence of prothrombotic disorders. Treated CVT was associated with a good prognosis. CVT is a frequent neurological manifestation of BD. When treated, BD-associated CVT bears a good prognosis. There is insufficient information regarding the role of concomitant prothrombotic disorders and specific treatments. [ABSTRACT FROM AUTHOR]

Copyright of Archives of the Turkish Dermatology & Venerology / Turkderm is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Archives of the Turkish Dermatology & Venerology / Turkderm is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cerebral venous thrombosis (CVT) is caused by various etiologies. In Mediterranean and Middle Eastern countries, Behçet’s disease (BD) is one of the leading causes of CVT. We aimed to evaluate any differences in CVT patients with and without BD. All registered patients with CVT were evaluated retrospectively. Clinical, neuroradiological findings and follow-up data were compared between patients with BD and patients with other etiologies. There were 36 patients with CVT and BD, and 32 patients with CVT related to other etiological causes. BD patients were younger (median age at onset 26 vs. 39 years; P < 0.001), and there was a male preponderance (28 males, 8 females) as compared to the non-BD group (10 males, 22 females; P < 0.001). Onset was frequently acute in the non-BD group, and it was subacute or chronic in the BD group. Hemi/quadriparesis, aphasia and seizures were significantly more common ( P < 0.001) in the non-BD group. In the BD group 94% of the patients presented with symptoms of isolated intracranial hypertension ( P < 0.001). Venous infarcts were observed in 63% of the patients with other causes and in 6% of the patients with BD ( P < 0.001). At admission 97% of the patients in the BD group and 41% of the patients in the non-BD group had a modified Rankin score of 0–2. Outcome was good in all of the patients with BD and in 91% of patients with other causes. Clinical recurrences were seen in six patients with BD and in one patient without BD. CVT associated with BD has a subacute onset, mostly presents with signs of isolated intracranial hypertension and venous infarction rarely develops; these features distinguish CVT due to BD from those with other causes. [ABSTRACT FROM AUTHOR]

Background: Mucocutaneous type of Behcet’s disease (MCBD) is a multisystemic inflammatory disease with oral and genital ulcers with or without skin lesions. Methods: A solid phase, two-site sequential chemiluminescent immunometric assay was used to measure serum levels of interleukin (IL)-6, IL-8 and tumour necrosis factor (TNF)-α in 54 normal control subjects and in 64 MCBD patients before and after treatment with levamisole plus colchicine. Results: We found that 67%, 83% or 67% of MCBD patients had a serum IL-6, IL-8 or TNF-α level greater than the upper normal limit of 4.7, 8.7 or 7.4 pg/ml, respectively. The mean serum level of IL-6 (9.9 ± 2.4 pg/ml, P < 0.005), IL-8 (107.5 ± 21.4 pg/ml, P < 0.001) or TNF-α (22.5 ± 4.1 pg/ml, P < 0.001) in 64 MCBD patients was significantly higher than that (2.1 ± 0.2, 5.7 ± 0.2 or 3.8 ± 0.2 pg/ml for IL-6, IL-8 or TNF-α level, respectively) in normal control subjects. In 43 MCBD patients with all the serum IL-6, IL-8 and TNF-α levels higher than their upper normal limits, treatment with levamisole plus colchicine for a period of 0.5–11.5 (mean, 3.2 ± 2.4) months could significantly reduce the mean serum IL-6, IL-8 and TNF-α levels from 9.0 ± 1.7 to 1.6 ± 0.2 pg/ml ( P < 0.001), 134.6 ± 28.2–6.0 ± 0.4 pg/ml ( P < 0.001) and 25.7 ± 5.6–3.5 ± 0.4 pg/ml ( P < 0.001), respectively. Conclusions: Treatment with levamisole and colchicine can result in a significant reduction of serum IL-6, IL-8 or TNF-α level in MCBD patients. [ABSTRACT FROM AUTHOR]

Background Behçet’s disease (BD) is a multisystemic chronic inflammatory disease with unknown aetiology. Interleukin (IL)-12, which is involved in the pathogenesis of BD, is a 70-kDa cytokine made of p35 and p40 subunits. Recently, IL-23, which is composed of a p19 subunit and a shared p40 subunit of IL-12, was discovered; as a consequence, this raises the need to re-examine previous IL-12 reports to determine whether IL-23 is also involved in BD pathogenesis. Objectives To determine whether there are changes in IL-23 in skin lesions and sera of patients with BD. Methods For quantitative reverse transcription–polymerase chain reaction, the total cellular RNA of erythema nodosum (EN)-like skin lesions from patients with BD, psoriasis skin lesions and skin biopsy samples from normal individuals was analysed. To determine cytokine levels, sera from patients with BD and normal individuals were analysed. Results Increased IL-23 p19 mRNA levels were observed for both EN-like lesions of patients with BD and skin lesions of patients with psoriasis compared with normal individuals. Although we observed an elevation of IL-12/23 p40 mRNA expression in the BD lesions, this was not significant. Moreover, the levels of IL-12 p35 mRNA in BD lesions were also not significantly different from the levels in normal control skin. In addition, no significant changes were detected in serum IL-12 and IL-23 levels between patients with BD and normal control individuals, or in patients with BD before and after treatment. Conclusions Increased expression of IL-23 p19 mRNA in BD lesions suggests that IL-23 may be associated with the development of the EN-like lesions in patients with active BD. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the efficacy of immunosuppressive therapy alone with that of combination therapy involving immunosuppressants and anticoagulation for the treatment of venous thrombosis in Behcet’s disease (BD). A retrospective analysis was made of 37 patients with venous thrombosis in BD. BD patients with venous thrombosis were divided into three groups: one group ( N = 16) received immunosuppressive therapy alone, another group ( N = 17) received immunosuppressant and anticoagulation combination therapy, and the third group ( N = 4) received anticoagulation therapy only. Clinical and laboratory parameters and the recurrence of venous thrombosis were assessed. Venous thrombosis in BD appeared to have a more diffuse pattern than idiopathic type and a predilection for lower limbs. The most commonly involved sites were the superficial and common femoral veins. Recurrence of venous thrombosis occurred in two cases in the immunosuppressant group (12.5%), one case in the combination therapy group (5.9%), and three cases in the anticoagulant group (75%). No significant difference was found between recurrence in the immunosuppressant and combination therapy groups. Acute phase reactants were elevated in all six patients at the time of venous thrombosis recurrence. Our study suggests that immunosuppressive therapy is essential and that anticoagulation therapy might not be required for the treatment of deep venous thrombosis associated with BD. [ABSTRACT FROM AUTHOR]

Interleukin-8 (IL-8), a CXC chemokine that recruits and activates inflammatory cells, plays a critical role in the pathogenesis of Behcet’s disease (BD). To investigate the association of the genetic polymorphism of IL-8 and BD, we genotyped IL-8 −845 T/C, −738 T/A, −353 A/T, −251 A/T, +293 G/T, +678 T/C and receptors CXCR-1 +2607 G/C and CXCR-2 +785 C/T polymorphisms in 119 Korean patients with BD and 119 age- and sex-matched healthy blood donors. Then, single nucleotide polymorphisms (SNPs) and haplotypes were analyzed between patients and controls. There were no SNPs associated with BD. However, the frequency of haplotype TAT inferred from SNPs, IL-8 −353 A/T, −251 A/T and +678 T/C, was significantly higher in patients with BD than controls (5.9 vs 0.0%, P = 0.0001), as was haplotype ATC (6.7 vs 0.0%, P < 0.0001). The haplotype difference was still valid in human leukocyte antigen-B51-negative subjects. In conclusion, we found a significant difference in the distribution of IL-8 gene haplotypes between patients with BD and healthy controls. These results suggest that the genetic polymorphisms of proinflammatory chemokine IL-8 can contribute to the pathogenesis of BD. [ABSTRACT FROM AUTHOR]

Objective: Although the pathogenesis of Behcet's disease (BD) is unknown, immune dysfunction appears to be involved. To improve understanding of the role of T cells and cytokines in BD, the current study analysed the localization and extent of expression of T cell subsets, cytokines, chemokines, and chemokine receptors in oral ulcers from BD patients and for comparison in oral ulcers from patients with recurrent aphthous stomatitis (RAS), as well as in healthy oral mucosa.Methods: Biopsies from oral ulcers of 25 BD patients and 19 RAS patients and oral mucosa from six healthy volunteers were immunoperoxidase stained.Results: Both CD4- and CD8-positive T cells were present in the oral ulcers of BD and RAS patients. The T helper (Th)1 cytokines interleukin (IL)-12, interferon (IFN)-gamma, and tumour necrosis factor (TNF)alpha and the Th1-associated chemokine receptors CCR5 and CXCR3 were increased in both patient groups as compared to normal controls, indicating the involvement of a Th1 immune response in the immunopathology of both BD and RAS. However, the Th2 cytokine IL-4 was only observed in oral ulcers of BD patients but not in RAS patients.Conclusion: This is the first study that shows the presence of pro-inflammatory cytokines, as well as Th1-associated chemokine receptors, in the oral ulcers of BD patients, as well as RAS patients, at a protein level. However, the expression of the Th2 cytokine IL-4 within the oral lesions of only BD patients is suggestive of a more complex antigenic stimuli in BD patients compared with RAS patients. [ABSTRACT FROM AUTHOR]

Purpose. – To describe epidemiological and clinical characteristics of neurological involvement in Behc¸et’s disease (BD) and to determine a subgroup of patients at high risk for this complication.Patients and methods. – The medical notes of 105 patients with BD fulfilling the criteria of the international Study Group for Behc¸et’s disease were retrospectively reviewed. Patients were divided into two groups according to the presence (group 1) or not (group 2) of neurological and/or psychiatric involvement attributable to BD. The epidemiological, clinical and genetic (HLA B51 and MICA 6 frequency) features in the two groups were analysed and compared using the Kruskall-Wallis and the chi-square tests.Results. – Twenty-seven patients (25.7%) had clinical evidence of neurological involvement. They were 20 men and 7 women. The mean age at neurological onset was 34.26 ± 8.79 years. Nineteen patients (70.3%) had meningoparenchymal “MP” central nervous system involvement (brainstem: 9, hemispheric involvement: 6, spinal cord: 4, psychiatric involvement: 2, isolated pyramidal signs: 1, aseptic meningitis:1). Seven patients (25.9%) had cerebral large vessels involvement that is cerebral angio-Behc¸et “CAB” (intracranial hypertension: 5 cases due to cerebral venous thrombosis: 3 and pseudotumor cerebri: 2, cerebral haemorrhage: 1, cerebral arterial thrombosis: 1). One patient (3.7%) had both “MP” and “CAB” involvement. Headache was significantly more frequent in non-parenchymal patients. In group 1, complete recovery or improvement with mild neurological impairment was seen in 13 cases, improvement with severe disability in 3 cases, worsening in 1case, the course was stationary in 1 case and 3 patients died (11.2%). Arterial aneurysms were significantly more frequent in “CAB” subgroups than in subgroup 2.Conclusion. – Frequency of neurological involvements in BD was high in our study. Arterial aneurysms seem to be a risk factor to these complications. Cerebral angio-Behc¸et appears to be a protector factor against uveitis. [ABSTRACT FROM AUTHOR]

Behçet's disease represents a multisystemic inflammatory disease characterized by recurrent oral ulcers, genital ulcers, and uveitis. Although vascular attack and thrombosis are not major complications in Behçet's disease, they can still pose risks that must not be overlooked. In this paper, we reported that a 25-year-old female Behçet's disease patient with complete thrombotic obstruction of the inferior vena cava that was successfully treated by aspiration thrombectomy and balloon angioplasty. The procedure produced marked symptomatic improvement. Currently, data about the treatment and the prophylaxis of thrombotic events in Behçet's disease are lacking. In this case report, we hope to discuss the future direction of such studies, how we understand the mechanism of Behçet's disease hypercoagulability, and which treatments can improve thrombotic tendencies in Behçet's disease. [ABSTRACT FROM AUTHOR]

The aim of the present study was to describe a case of Behçet’s disease revealed by a recurrent meningitis and to review literature on these two conditions. We describe the case of a 25-year-old man who presented four episodes of recurrent meningitis without any locoregional cause and developed oral and genital ulcerations few months later. Behçet’s disease is a chronic, multisystemic disorder with variable prevalence in different geographical areas. Its neurological manifestations are well recognized. Both central and peripheral nervous systems can be involved. Recurrent meningitis in Behçet’s disease is exceptional. To our knowledge, only two cases reported recurrent meningitis as initial manifestation of Behçet’s disease. This case report underscores another facet of neurological manifestations of Behçet’s disease. [ABSTRACT FROM AUTHOR]