Inhibition of ERAP1 represses HLA-B27 free heavy chains expression on polarized macrophages and interrupts NK cells activation and function from ankylosing spondylitis.

BACKGROUND: We aimed to assess if Endoplasmic reticulum aminopeptidase 1 (ERAP1) polymorphisms might impress Human leukocyte antigen (HLA)-B27-free heavy chains (FHCs) expression on macrophages and eventually NK cell activation in Ankylosing spondylitis (AS). METHODS: Blood samples were obtained from 10 HLAB27+ patients with protective and 10 HLAB27+ patients with non-protective genotype. Monocytes were isolated and polarized toward M1 and M2 macrophages. ERAP1 was inhibited in macrophages, which were then co-cultured with autologous NK cells. RESULTS: Expression of HLA-B27-FHCs on M1 and M2 macrophages was reduced in patients with protective ERAP1 genotype. Co-culturing ERAP1-inhibited M1 macrophages and NK cells from patients with protective genotype resulted in downmodulation of CD69 and CD107a markers on NK cells and reduced number of IFN-γ+ NK cells compared to that of patients with non-protective genotypes. CONCLUSION: Inhibition of ERAP1 activity, by diminishing NK activation, may have therapeutic value in treating AS patients.

Prevalence of SARS-CoV-2 Specific Antibodies in Asymptomatic Hemodialysis Patients.

BACKGROUND: Since the outbreak of the new coronavirus pandemic, the importance of carrying out an infection check to prevent acquisition and transmission among end-stage renal disease patients (ESRD) under maintenance hemodialysis (MHD) has become a major concern in the health care system. Applying serology screening tests could enlighten the view with regards to disease prevalence in dialysis wards. METHODS: We subjected 328 end-stage renal disease patients to maintenance hemodialysis. After dividing patients into suspicious and non-suspicious groups for COVID-19 infection based on their clinical manifestation, they were investigated for SARS-CoV-2 specific IgM and IgG screening against nucleoprotein (NP), spike protein (SP), and receptor-binding domain (RBD), utilizing our recently developed ELISA tests. RESULTS: We found that approximately 10.1% of asymptomatically tested cases were antibody positive. Although IgG positivity showed a higher prevalence than IgM across all three virus antigen subunits, there were no significant differences among mentioned immunoglobulins of the studied groups. The most prevalent antibody was from the IgG subtype against virus nucleoprotein (NP), while the lowest prevalence was attributed to receptor-binding domain (RBD) IgM. CONCLUSION: High seropositive rate among asymptomatic end-stage renal disease patients, as a sample of high-risk population, reflected the importance of considering SARS-CoV-2 specific antibody screening for disease containment.

Janus kinase inhibitors: A therapeutic strategy for cancer and autoimmune diseases.

Many cytokines are crucial drivers of cancers and autoimmune conditions. These proteins bind to receptors and signal their responses through Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathways. Genetic variations in the JAK-STAT pathway are correlated with the increased risk of cancers, autoimmunity as well as inflammatory diseases. Targeting JAKs and STATs can be a safe and efficacious strategy for treating these diseases. Tofacitinib, as the first JAK inhibitor, is approved for rheumatoid arthritis therapy. Also, many other JAK inhibitors have been proven or are in various phases of clinical trials for various diseases. At present, small-molecule JAK inhibitors are considered as a novel category of drugs in the treatment of cancer and immune-mediated diseases.

The role of B cells in the immunopathogenesis of multiple sclerosis.

There is ongoing debate on how B cells contribute to the pathogenesis of multiple sclerosis (MS). The success of B-cell targeting therapies in MS highlighted the role of B cells, particularly the antibody-independent functions of these cells such as antigen presentation to T cells and modulation of the function of T cells and myeloid cells by secreting pathogenic and/or protective cytokines in the central nervous system. Here, we discuss the role of different antibody-dependent and antibody-independent functions of B cells in MS disease activity and progression proposing new therapeutic strategies for the optimization of B-cell targeting treatments.

Evaluation of DNA methylation status of toll-like receptors 2 and 4 promoters in Behcet's disease.

BACKGROUND: Altered innate immune function plays an important role in the initiation of inflammatory response in Behcet's disease (BD). Toll-like receptors (TLRs) are the master regulators of the innate immune system. Because the role of TLRs remains unknown in the pathogenesis of BD, the present study aimed to evaluate the expression levels and methylation status of the TLR2 and TLR4 promoters in patients with BD. METHODS: In the present study, Iranian Azeri BD patients (n = 47) with an active (n = 22) and inactive (n = 25) period, and healthy controls (n = 61), were matched according to age, sex and ethnicity. TLR2 and TLR4 genes promoter CpG islands were predicted with the Eukaryotic Promoter Database (https://epd.vital-it.ch). Methylated DNA immunoprecipitation (MeDIP) was conducted. RESULTS: The results showed that mRNA of TLR4 was significantly increased in the peripheral blood mononuclear cells (PBMCs) of BD patients with an active phase compared to the control group. Differences in mRNA of TLR4 between the inactive BD and control groups were not significant. Differences in TLR2 mRNA levels in the PBMCs of the active and inactive phase BD and control groups were not significant. The methylation rate of TLR4 gene promoter was significantly lower in the active and inactive BD groups compared to the control group. The difference between the active and inactive BD groups was not significant. There was no significant difference in the methylation rates of the TLR2 gene between studied groups. CONCLUSIONS: Our preliminary findings suggest that the hypomethylation of TLR4 gene may be involved in the pathogenesis of BD via increasing TLR4 expression.

siRNA-mediated silencing of CD44 delivered by Jet Pei enhanced Doxorubicin chemo sensitivity and altered miRNA expression in human breast cancer cell line (MDA-MB468).

CD44, as a superficial cellular glycoprotein, is an essential factor in cell-cell and cell-matrix interaction. The CD44 expression level has been substantially up-regulated in breast cancer, and this upregulation facilitates tumor proliferation and angiogenesis. This study aims to evaluate the combination therapy of Jet Pei/CD44-specific-siRNA/doxorubicin in breast cancer MDA-MB468 cell line. The MTT assay, wound healing test, colony formation assay, DAPI staining, and flow cytometry were performed to investigate the tumoral cell viability, migration, clonogenesis, and apoptosis progression. The quantitative real-time PCR (qRT-PCR) was performed to demonstrate the CD44 expression level. Finally, the effect of CD44 silencing on the expression of VEGF, CXCR4, MMP9, and MiR-142-3p was measured. The combination of CD44-specific-siRNA with doxorubicin decreased tumoral metastasis, proliferation, invasion, and migration, and increased apoptosis in MDA-MB468 cells. In conclusions, CD44 can serve as a therapeutic target in breast cancer. Moreover, the combination therapy of CD44-specific-siRNA with doxorubicin can be a promising treatment for patients with breast cancer.

mTOR Signaling pathway as a master regulator of memory CD8+ T-cells, Th17, and NK cells development and their functional properties.

The mammalian target of rapamycin (mTOR) is a member of the evolutionary phosphatidylinositol kinase-related kinases (PIKKs). mTOR plays a pivotal role in the regulation of diverse aspects of cellular physiology such as body metabolism, cell growth, protein synthesis, cell size, autophagy, and cell differentiation. Immunologically, mTOR has a fundamental part in controlling and shaping diverse functions of innate and adaptive immune cells, in particular, T-cell subsets differentiation, survival, and metabolic reprogramming to ultimately regulate the fate of diverse immune cell types. Researchers report that rapamycin, a selective mTOR inhibitor, and immunosuppressive agent, has surprising immunostimulatory effects on inducing both quantitative and qualitative aspects of virus-specific memory CD8+ T-cells differentiation and homeostasis in a T-cell-intrinsic manner. The mTOR signaling pathway also plays a critical role in dictating the outcome of regulatory T cells (Treg), T helper 17 (Th17) cells, and natural killer (NK) cells proliferation and maturation, as well as the effector functions and cytotoxic properties of NK cells. Manipulation of mTOR activity is a critical therapeutic approach for pharmacological agents that seek to inhibit mTOR. This approach should enhance specific memory CD8 + T-cells responses and induce fully functional effector properties of NK cells to provoke their antitumor and antiviral activities.

Altered frequency of CD8+ CD11c+ T cells and expression of immunosuppressive molecules in lymphoid organs of mouse model of colorectal cancer.

CD11c is a member of the ß2-integrin family typically used to define myeloid dendritic cells (DCs). Recent reports identify CD11c-expressing CD8+ T cells as a new subset of CD8+ regulatory T cells (Treg). Evidence exists that CD11c+ CD8+ T cells may exert their effector or regulatory functions under different conditions. To date, no studies have addressed the frequency of CD11c+ T cells in cancer. Limited evidence exists in terms of expression of immune-checkpoint receptors, programmed cell death protein 1 (PD-1) and T-lymphocyte-associated antigen 4 (CTLA-4), as well as forkhead box P3 (Foxp3) in mouse lymphoid organs. Here, we have assessed CD11c+ CD8+ and CD11c+ CD4+ T cells, Foxp3, PD-1, and CTLA-4 expressing CD4+ T cells and CD8+ T cells in different tissues from three groups of male BALB/c mice-young, mature, and those with colorectal cancer (CRC). Analysis of CD3+ CD11c+ T cells in the bone marrow (BM), spleen, and lymph nodes (LN) in each group showed a higher percentage of CD3+ CD11c+ T cells in the BM from all groups and in the lymphoid organs of the cancer group compared with the young and mature groups. CD4low and CD4high cell fractions in mice BM have different expression patterns for Foxp3 and CTLA-4. We have observed a higher frequency of CD8+ PD-1+ T cells in the BM, spleen, and LN of CRC mice compared with normal mice. T-cell exhaustion is associated with inhibitory receptor PD-1. According to the regulatory roles of CD11c expression in CD8+ T cells, we have proposed that the elevated percentage of CD11c, Foxp3, CTLA-4, and PD-1 expressing T cells were associated with immune response dysregulation in CRC.

Diagnostic biomarker and therapeutic target applications of miR-326 in cancers: A systematic review.

MicroRNAs (miRNAs) are endogenous mediators of RNA interference and have key roles in the modulation of gene expression under healthy, inflamed, stimulated, carcinogenic, or other cells, and tissues of a pathological state. Many studies have proved the association between miRNAs and cancer. The role of miR-326 as a tumor suppressor miRNA in much human cancer confirmed. We will explain the history and the role of miRNAs changes, especially miR-326 in cancers and other pathological conditions. Attuned with these facts, this review highlights recent preclinical and clinical research performed on miRNAs as novel promising diagnostic biomarkers of patients at early stages, prediction of prognosis, and monitoring of the patients in response to treatment. All related publications retrieved from the PubMed database, with keywords such as epigenetic, miRNA, microRNA, miR-326, cancer, diagnostic biomarker, and therapeutic target similar terms from 1899 to 2018 with limitations in the English language. Recently, researchers have focused on the impacts of miRNAs and their association in inflammatory, autoinflammatory, and cancerous conditions. Recent studies have suggested a major pathogenic role in cancers and autoinflammatory diseases. Investigations have explained the role of miRNAs in cancers, autoimmunity, and autoinflammatory diseases, and so on. The miRNA-326 expression has an important role in cancer conditions and other diseases.

Disturbed Th17/Treg balance, cytokines, and miRNAs in peripheral blood of patients with Behcet's disease.

Impaired inflammatory immune cells have been implicated in the pathogenesis of Behcet's disease (BD). In the current study, we aimed to evaluate the frequency of T helper (Th) 17 and regulatory T (Treg) cells, cytokine secretion, the expression of transcription factors related to Th17 and Treg cells, and microRNAs (miRNAs) targeting these transcription factors in BD patients. Blood samples from 47 BD patients and 58 healthy subjects were drawn, and the peripheral blood mononuclear cells (PBMCs) were separated and isolated. The frequency of Th17 and Treg cells was assessed using flow cytometry. Transcription factors related to these cells and miRNAs targeting these transcription factors were quantified using real-time polymerase chain reaction. Finally, the levels of associated cytokines were measured using enzyme-linked immunosorbent assay. A significant reduction in the percentage of Treg cell frequency and the levels of interleukin (IL)-10 and forkhead box P3 messenger RNA (mRNA) expressions were observed. The proportion of Th17 cells was notably increased, which was accompanied by a increased levels of IL-17, IL-23, and retinoic acid-related orphan receptor ɣ (RORɣt) mRNA expressions in BD patients. The level of Th17-associated cytokines in the supernatant was found to be elevated in BD patients. T-cell-associated miRNA expression levels, miR-25, miR-106b, miR-326, and miR-93 were significantly upregulated, while miR-146a and miR-155 levels were lower in PBMCs of patients with BD when compared with the controls. The increase in the proportion of Th17 cells alongside the decrease in Treg cells are possibly the involving factors in the pathogenesis of BD. Therefore, the evaluation of immune cells and related miRNA profile may serve as both prognostic biomarker and therapeutic approach in treating patients with BD.

Downregulation of miR-146a promotes cell migration in Helicobacter pylori-negative gastric cancer.

microRNAs (miRs) are short noncoding RNAs that post-transcriptionally suppress gene expression. miR-146a acts as an oncogene or a tumor suppressor in various cancers, including gastric cancer, but it is unclear what determines whether miR-146a is oncogenic or tumor suppressive and the molecular mechanisms are still largely unknown. The aim of this study was to investigate the role of miR-146a in gastric cancer, by focusing on its expression in patients who were negative for Helicobacter pylori and its reduced and increased expression effect in vitro. Twenty gastric cancer patients who were negative for H. pylori infection were selected and the expression levels of miRNA-146a in these gastric tumors, in their matched normal gastric tissues and in gastric cancer cell lines with varying tumorigenic potential was measured. Further, the impact of increased and decreased miR-146a expression levels on the expression of predicted target genes, cell migration, viability, proliferation, and apoptosis was examined, respectively. Our results for the first time indicated that miR-146a is downregulated in H. pylori-negative gastric cancers and suggests that H. pylori infection determines whether miR-146a acts as an oncogene or tumor suppressor. The level of miR-146a expression inversely correlates with the tumorigenicity of three gastric cancer cell lines and low miR-146a expression predicts poor recurrence-free survival. It was also found that miR-146a reduces the expression levels of the prometastatic genes and suppresses MKN-45 cell migration. Functional studies showed that miR-146a acts as a tumor suppressor miR and identifies miR-146a as a candidate for antimetastatic miRNA replacement therapy for gastric cancer patients.

The role of innate lymphoid cells in health and disease.

Innate lymphoid cells (ILCs) are kind of innate immune cells which can be divided into three main subsets according to their cytokine release profile, transcription factors, and surface markers. ILCs affect the initial stages of immunity in response to microbes and participate in immunity, inflammation, and tissue repair. ILCs modulate immunity through resistance to the pathogens and regulation of autoimmune inflammation and metabolic homeostasis. Therefore dysregulation of ILCs may lead to chronic pathologies such as allergies (i.e., asthma), inflammation (i.e., inflammatory bowel disease), and autoimmunity (i.e., psoriasis, atopic dermatitis, rheumatoid arthritis, multiple sclerosis, and ankylosing spondylitis). Regarding the critical role of ILCs in the regulation of immune system, the elucidation of their function in different conditions makes an interesting target for improvement of novel therapeutic approach to modulate an immune response in different disease context.

Nanocurcumin restores aberrant miRNA expression profile in multiple sclerosis, randomized, double-blind, placebo-controlled trial.

In the current study, we aimed to identify nanocurcumin effects on microRNAs (miRNAs) in the peripheral blood of patients with relapsing-remitting multiple sclerosis (RRMS). We intended to investigate the expression pattern of these miRNAs in experimental settings in vivo. The expression levels of the selected 27 miRNAs known to be involved in the regulation of immune responses were analyzed in 50 RRMS patients and 35 healthy controls. The miRNA expression profiles were investigated by quantitative PCR (qPCR) at baseline and after 6 months of nanocurcumin therapy. Our data revealed that the expression of a number of microRNAs including miR-16, miR-17-92, miR-27, miR-29b, miR-126, miR-128, miR-132, miR-155, miR-326, miR-550, miR-15a, miR-19b, miR-106b, miR-320a, miR-363, miR-31, miR-150, and miR-340 is regulated by nanocurcumin. The results of the current work indicate that nanocurcumin is able to restore the expression pattern of dysregulated miRNAs in MS patients. We discovered that some miRNAs are deregulated in untreated patients compared with healthy controls and nanocurcumin-treated patients. This is a new finding that might represent the potential contribution of these miRNAs to MS pathogenesis. Taken together, these data provide novel insights into miRNA-dependent regulation of the function of B and T cells in MS disease and enrich our understanding of the effects mediated by a therapeutic approach that targets B and T cells.

Hypermethylation of IL-10 gene is responsible for its low mRNA expression in Behçet's disease.

Interleukin-10 (IL-10), produced generally by monocyte, T helper type 2 (Th2), and regulatory T cells (Treg), plays a central role in controlling inflammatory responses and regulating the immune response of the IL-10 mRNA expression. It is significantly down-regulated in many autoimmune diseases such as Behçet's disease; this is mostly associated with more aggressive complications. Nevertheless, the essential molecular process for its low expression has not been completely realized. The aim of this project was attempted to estimate the gene expression, promoter methylation, and protein levels to IL-10's down-regulated expression. In this study, blood samples from 51 (4 missed) patients and 63 (2 missed) healthy controls were taken, with the mononuclear cells isolated by the Ficoll Protocol. DNA and RNA were then subsequently extracted. Promoter methylation levels were evaluated by MeDIP-qPCR. Following this, the extracted RNA was converted to cDNA using the RT-PCR method, with the expression of IL-10 later evaluated by Real-time PCR. And then, serum levels of IL-10 were measured using ELISA method. As we expected, the expression level of the IL-10 gene was seen to significantly decline in the patient group in comparison to the control. Also, the rate of promoter methylation was significantly higher in the IL-10 mRNA low expression group (patient group) compared to its high expression group (healthy group) (P < 0.001). We revealed that hypermethylation of promoter region was the principal defect for the IL-10 mRNA low expression in patients with Behçet's disease.

Correction to: Peripheral Th17/Treg imbalance in elderly patients with ischemic stroke.

In the original article the terms RORγt and GF-ß were misspelled throughout the text. They should read RORγt and TGF-ß instead. We apologize for the inconvenience. The original article has been corrected.

Peripheral Th17/Treg imbalance in elderly patients with ischemic stroke.

CD4+CD25+ regulatory T (Treg) cells and Th17 cells play important roles in peripheral immunity. Immune responses are main elements in the pathogenesis of ischemic stroke (IS). The contribution of Th17 cells in IS patients has not been proved, and whether the balance of Treg/Th17 cells is changed in IS patients remains unidentified. In the present study, we studied Th17 and Treg cell frequency, cytokine secretion, expression of transcription factors, and microRNAs related to Th17 and Treg cells differentiation, which is compared between IS patients and control group. Thirty patients with IS and 30 individuals as control group were enrolled in this study. The frequency of Th17 and Treg lymphocytes, the expression of transcription factors and microRNAs related to these cells, and the serum levels of associated cytokines were assessed by flow cytometry, real-time PCR, and ELISA, respectively. A significant reduction in proportion of peripheral Treg cell frequency and the levels of TGF-ß and FOXP3 expression were observed in patients with IS compared with controls, while the proportions of Th17 were increased dramatically, and these effects were along with increases in the levels of IL-17A and RORγt expression in IS patients. The levels of mir-326 and mir-106b-25 expression were increased in patients with IS. These studies suggest that the increase in proportion of Th17 cells and decrease in Treg cells might contribute to the pathogenesis of IS. Manipulating the balance between Tregs and Th17 cells might be helpful for the treatment of IS.

Investigation of Fc Receptor-Like 3 (FCRL-3) Gene Polymorphism (rs7528684) with Susceptibility to Allergic Asthma in Iranian North-Western Azeri Population.

BACKGROUND: Asthma is a clinical setting in which multiple cellular and molecular mechanisms are involved. Additionally, increasing genetic studies have provided evidence that single nucleotide polymorphisms (SNPs) in asthma relevant genes confer susceptibility to the disease. Fc receptor-like (FCRL) 3, a transmembrane molecule basically involved in B-cell signaling, mediates immune-disorders including allergy. Aim of study was to investigate the possible association of rs7528684 SNP in FCRL3 gene with a predisposition to allergic asthma in Iranian North-western Azeri population. METHODS: The frequency of genotypes and alleles of rs7528684 SNP in the FCRL3 gene was determined using the TaqMan genotyping method in 191 asthmatic patients and 186 healthy controls. RESULTS: The most frequent genotype in patients and control groups were CT (n = 81, 42.4%) and TT (n = 76, 40.9%), respectively. Statistical analysis showed no significant difference in genotype frequency (p = 0.81) and also in frequency of C and T alleles (p = 0.52) between two groups. CONCLUSIONS: Our results revealed no association between the rs7528684 SNP with susceptibility to allergic asthma in the included population. More studies in different ethnic groups will result in more valid conclusions.

Evaluation of TLR9 expression on PBMCs and CpG ODN-TLR9 ligation on IFN-α production in SLE patients.

CONTEXT: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by autoreactive antibodies. Recent findings revealed the importance of innate immune responses, especially Toll-like receptors (TLRs) in the pathogenesis of SLE. OBJECTIVE: In this study, the level of TLR9 expression on peripheral blood mononuclear cells (PBMCs) was analyzed. The levels of produced IFN-α were also measured in supernatant of PBMCs from SLE patients and healthy controls after stimulation with CpG ODN2216 which is a plasmocytoid dendritic cell (pDC)-specific TLR9 ligand. MATERIALS AND METHODS: TLR9 expression was analyzed by real-time polymerase chain reaction (PCR) and flow cytometry in 35 SLE patients and 38 healthy controls and IFN-α concentration was measured in supernatants using enzyme-linked immunosorbent assay (ELISA). RESULTS: The results showed that the TLR9 expression in the mRNA and the protein level was significantly higher in PBMCs from SLE patients. However, IFN-α concentration in patients and controls significantly increased in response to CpG stimulation but this increase was significantly higher in healthy controls compared with SLE patients. Our results do not show any association between taking hydroxychloroquine and reduction in IFN-α production in SLE patients. DISCUSSION AND CONCLUSIONS: Regarding the findings of the study, there is the possibility that TLR9 has played a role in SLE pathogenesis, and consequently it implies that TLRs can be considered to be the therapeutic targets for systemic autoimmunity. We may conclude that PBMCs in patients are functionally impaired in response to TLR ligation via innate response stimulating pathogen-associated molecular patterns (PAMPs).

IL-27 Gene Polymorphisms in Iranian Patients with Behcet's Disease.

BACKGROUND: Behcet's Disease (BD) is a chronic systemic inflammatory disease of unknown etiology, principally characterized by relapsing periods of a broad range of clinical symptoms. Cytokines play fundamental roles in the pathogenesis of BD. Polymorphisms within cytokine genes have been found to play a pathogenic role in the development of autoimmune/inflammatory disorders. Interleukin 27 (IL-27), a new pro-/anti-inflammatory cytokine, is a great candidate for chronic inflammatory disease studies. The purpose of this study was to investigate a possible association between polymorphisms in the IL-27 gene and susceptibility to BD. METHODS: Fifty Iranian patients with BD and one hundred healthy individuals were examined for rs153109A/G and rs181206T/C IL-27 gene single nucleotide polymorphisms using RFLP-PCR and ARMS-PCR, respectively. Allele and genotype distributions were compared between groups using chi-square or Fisher's exact test. RESULTS: Frequencies of the rs153109AA genotype and rs153109A allele were statistically higher in BD patients compared with the control group (p = 0.034 and p = 0.011, respectively). The genotype and allele frequencies of rs181206 T/C polymorphism in BD patients were not significantly different from those of healthy controls. CONCLUSIONS: Present findings demonstrate for the first time that the IL-27 gene rs153109 A/G SNP may be involved in susceptibility to BD in the Iranian population.

A Single Nucleotide Polymorphism in the FOXP3 Gene Associated with Behçet's Disease in an Iranian Population.

UNLABELLED: Background: Behçet's Disease (BD) is a rare autoimmune disease that involves the dysfunction of regulatory T cells. FOXP3 is a key transcription factor in the development and function of T(reg) cells. Recent studies have shown SNPs in the FOXP3 contribute to the susceptibility to some autoimmune disorders. METHODS: To clarify the association between the FOXP3 gene and the risk of BD, 50 patients diagnosed with BD and 50 healthy controls from north-western Iran were genotyped by PCR-RFLP (Mun I and Pst I) for two SNPs including rs3761547 (-3499T/C) and rs3761548 (-3279 C/A) in the promoter region of the FOXP3 gene. In addition, a 506 bp nucleotide sequence of FOXP3 promoter was analyzed. RESULTS: The allele -3279 C/A was significantly associated with BD [p = 0.002; odds ratio (OR) = 3.841; 95% confidence interval (CI) 1.610 - 9.161]; whereas, there was no contribution of the FOXP3 polymorphism -3499T/C to BD [(p = 0.084); (OR = 0.348, 95% CI = 0.101 - 1.195)]. Meanwhile, sequence analysis showed 100% similarity in both controls and BD patient groups. CONCLUSIONS: Therefore, the SNP rs3761548 in the FOXP3 gene appears to contribute to the risk of Behçet's disease among the north-western Iranian population.