Leukocytoclastic vasculitis in a patient with ankylosing spondylitis: A case report.

Key Clinical Message: Although the concurrent occurrence of vasculitis with AS is uncommon, when patients diagnosed with AS exhibit symptoms including skin petechiae, purpura, abdominal discomfort, malaise, elevated ESR, and reduced complement levels, vigilant monitoring for vasculitis is advisable following the exclusion of secondary vasculitis triggers such as malignancies, infections, and pharmaceutical agents. Abstract: The primary characteristic of ankylosing spondylitis (AS) involves inflammation occurring within the sacroiliac joint and the spine, leading to destruction and eventual ankylosis. A notably infrequent complication associated with AS is vasculitis, with limited reports linking AS to vasculitis. This case study documents a 48-year-old male, diagnosed with HLA-B27-positive AS for the past 15 years, who developed abdominal pain and skin lesions following the cessation of his medication on his own. Subsequent clinical evaluations identified leukocytoclastic vasculitis (LCV) related to AS after excluding all other potential causes of LCV, including drug-related sources, cancer, hepatitis B and C viruses, Henoch-Schönlein purpura (HSP), and IgA nephropathy.

Predictors of medications-free and long-term remission in anti-neutrophil cytoplasmic antibody-associated vasculitis: Real-world evidence.

BACKGROUND AND AIM: In this study, we report the outcomes of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in daily practice based on Connective Tissue Diseases Research Center-Vasculitis Registry (CTDRC-VR) data. METHODS: Patients were included if they were 18 years or older, had a diagnosis of the groups of AAV based on 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis and microscopic polyangiitis, and were followed for a period longer than 2 years or were died. Complete clinical remission was defined as granulomatosis with polyangiitis (BVAS/GPA) of 0. Sustained remission was defined as a complete clinical remission for at least six months and tapering prednisolone dose to ≤ 7.5 mg/d. Long-term remission was defined as complete clinical remission for ≥ 5 years and tapering prednisolone dose to ≤ 7.5 mg/d. Medications-free remission was defined as complete clinical remission and discontinuation of glucocorticoids, cytotoxic medications and biologics. RESULTS: Sixty patients with AAV were enrolled in this study. Sustained and long-term remission were developed in 91.7 and 72.1 percent of patients, respectively. Relapse was developed in 27 (45%) patients. Medications-free remission was developed in 23 (33.3%) patients. Vasculitis induced damage was developed in 40 (66.7%) patients. Patients with damage had significantly lower age and higher BVAS at the baseline. Upper airway and renal involvement, and non-adherence in patients with damage was significantly more common. CONCLUSIONS: Induction therapy leads to long-term and medications-free remission in 72% and 38% of patients with AAV, respectively.

Cigarette smoking and risk of adult-onset Still disease: a propensity score matching analysis.

BACKGROUND: Environmental factors play an important role in the pathogenesis of rheumatic diseases. Smoking is thought to be a risk factor for autoimmune rheumatic diseases. AIMS: The purpose of the present study was to assess the association between smoking and adult-onset Still disease (AOSD) and the effect of smoking on outcomes of this disease. METHODS: In this case-control study, patients with AOSD who met the Yamaguchi criteria, were older than 16 years at the disease onset and were in follow-up for at least 12 months were consecutively enrolled in the study. The outcome of AOSD was assessed by acquiring remission on treatment, remission off treatment, time to remission and rate of flare. The smoking status of participants was defined by direct or phone interviews. Individuals who had smoked daily for at least 6 months were defined as a smoker. We performed propensity score matching analyses by using four parameters, including age, sex, educational status and marital status. RESULTS: Propensity score matching resulted in 72 patients with AOSD and 216 matched controls. The number of ever smokers in the AOSD and control groups were 11 (15.3%) and 25 (11.6%) respectively. There was no significant increase in the risk of AOSD in multivariate analysis after adjustment for age, sex, marital status and educational level. There were no significant differences in the outcomes of AOSD between ever and never smokers. CONCLUSIONS: Smoking probably is not a risk factor for AOSD and did not affect the response to treatment.

An Exploration of Some Predictors of Quality of Life-Related to the Innate Immune System, Inflammation, and Disease Activity in Patients with Behcet's Syndrome: An Analytical Cross-sectional Study.

BACKGROUND: Behçet's disease (BD) has a growing prevalence in Silk Road countries. The aim of our cross-sectional study was to explore the clinical and molecular predictors of quality of life in BD patients. MATERIALS AND METHODS: One hundred and fifty consecutive Iranian BD patients with an age range between 20-50 years were included. The Leeds Behçet's disease quality of life (BDQoL) in Persian form was fulfilled to evaluate the quality of life. Anthropometric measurements were carried out using the calibrated scales. Iranian Behcet's Disease Dynamic Activity Measure (IBDDAM), Behcet's disease current activity form (BDCAF), and Total Inflammatory Activity Index (TIAI) were used to assess BD activity. mRNA expression of toll-like receptors 2 and 4 (TLR2 and TLR4) and tumor-necrosis-factor-alpha (TNF-α) levels in serum were measured by real-time polymerase chain reaction (PCR) and ELISA, respectively. Multiple linear backward regression at P = 0.1 was used to study the potential predictors of quality of life. RESULTS: TLR2 and BDCAF were shown to be the most important predictors of quality of life in BD patients by 22%. There were positive associations between them (ß = 0.326, p = 0.013 for BDCAF; ß = 0.366, p = 0.006 for TLR2) and BDQoL value. CONCLUSION: Higher TLR2 expression as a key protein in recognizing pathogens by innate immunity and BDCAF value as a comprehensive BD assessing scale contribute to poor quality of life among BD patients. Emphasizing therapeutically, approaches associated with lower TLR2 expression and BDCAF value can be considered in future studies.

Eosinophilic granulomatosis with polyangiitis following flu guard influenza vaccination: A case report.

Key Clinical Message: This case highlights a potential association between influenza vaccination and the development of eosinophilic granulomatosis with polyangiitis (EGPA), prompting the need for increased vigilance regarding vaccine-related autoimmune reactions. While causality remains unclear, clinicians should consider this possibility in patients presenting with EGPA-like symptoms shortly after vaccination. Abstract: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis characterized by tissue infiltration by eosinophils and hyper eosinophilia. We present a case of EGPA in a middle-aged man following influenza vaccination. The patient developed respiratory symptoms, skin lesions, joint pain, and neurological deficits. Diagnostic tests revealed eosinophilia, positive anti-neutrophil cytoplasmic antibodies, and elevated acute phase reactants. This report highlights a potential association between influenza vaccination and EGPA.

Castleman disease presenting as lymphadenopathy in a female with systemic lupus erythematosus: A rare case report.

Castleman disease is an infrequent disease that affects the lymph nodes and related tissues. The condition may manifest with lymphadenopathy, characterized by the enlargement of the lymph nodes, alongside additional symptoms such as high fever, nocturnal sweating, exhaustion, and loss of body mass. The diagnosis of Castleman disease typically entails a multifaceted approach that includes a physical examination, imaging modalities, and a biopsy of the lymph nodes that are affected. The selection of treatment modalities is contingent upon the classification and extent of the disease. Systemic lupus erythematosus (SLE) has been identified as a potential risk factor for the development of lymphoma, a condition that may manifest with lymphadenopathy resembling Castleman disease. Hence, it is crucial for individuals diagnosed with SLE and exhibiting lymphadenopathy to undergo a comprehensive assessment to exclude the possibility of any other associated disease. Although lymphadenopathy is a common symptom shared by both Castleman illness and SLE, these diseases have distinct etiologies and are treated in different ways. Seeking advice from a healthcare practitioner is crucial in order to obtain an accurate diagnosis and effective treatment. A 39-year-old female patient with a history of SLE since 18 years ago and lupus nephritis since 6 years ago which treated with Mycophenolic Acid 2 g daily, Hydroxychloroquine 400 mg daily, and low doses of Prednisolone. Also, Mycophenolic Acid has discontinued for her 5 months ago due to the reduction of proteinuria and the control of the disease. Although the association of Castleman Disease with SLE is infrequent, establishing a connection between them could prove advantageous in the treatment and etiology of diseases.

Outcomes of undifferentiated peripheral inflammatory arthritis in real-world practice. A longitudinal cohort study.

OBJECTIVES: Undifferentiated peripheral inflammatory arthritis (UPIA) may have 3 different courses, including evolution to differentiated arthritis, remaining undifferentiated, and self-limited course. The purpose of this study was to provide a real-world evidence for predictors of outcomes in UPIA in a longitudinal cohort of patients. METHODS: Patients enrolled in the CTDRC-UA cohort were screened for eligibility. Inclusion criteria were: (i) having synovitis in ≥ 1 joint, (ii) not meeting the criteria of any other rheumatic disease, (iii) having at least 2 visits per year, iv) included in the cohort during the period of 2004 to 2021, and (v) having active disease at cohort entry. Two hundred and three patients who met the inclusion criteria were followed up until January 2023. RESULTS: Medication-free remissions occurred in 42 (20.7%) cases. In 24 (11.8%) cases, the disease met the criteria of other rheumatic diseases, of which rheumatoid arthritis (RA) was the most common. In addition, joint damage occurred in 33 (16.3%) cases. Predictors of medication-free remissions were absence of comorbidity, starting a sustained remission at ≤ 6 months, and having no flare. Factors associated with disease evolution to RA were anti-citrullinated peptide antibody (ACPA) positivity, non-adherence to therapy, not going into sustained remission and having flare. Delay in treatment for > 3 months and being ACPA positive were the predictors of joint damage. CONCLUSION: Although the majority of UIPA cases treated with step-up combination therapy with DMARDs do not progress to RA, most require continued treatment and a few achieve medication-free remissions. Key Points • Undifferentiated peripheral inflammatory arthritis (UPIA) can progress to rheumatoid arthritis in 11% of cases; and lack of sustained remission, being anti-citrullinated peptide antibody positive, non-adherence to therapy, and having flare are its predictors. • Medication-free remissions occur in 21% of patients with UPIA; and absence of comorbidity, starting a sustained remission at ≤ 6 months, and having no flare are its predictors. • Initiating treatment in the window of opportunity may lead to a better joint outcome.

The effect of osteoporotic and non-osteoporotic individuals' T cell-derived exosomes on osteoblast cells' bone remodeling related genes expression and alkaline phosphatase activity.

OBJECTIVES: Osteoporosis is a common skeletal disorder attributed to age and is defined as a systematic degradation of bone mass and the microarchitecture leading to bone fractures. Exosomes have been reported in almost all biological fluids and during the failure of bone remodeling. 20 ml of blood samples were obtained from osteoporotic and non-osteoporotic postmenopausal women. After the isolation of peripheral blood mononuclear cells (PBMCs), T cells were separated via the magnetic-activated cell sorting (MACS) technique. Exosomes were driven from T cells of non-osteoporotic and osteoporotic volunteers. Subsequently, normal osteoblasts were treated with obtained T cell exosomes to assess osteoblastic function and gene expression. RESULTS: Runx2, type I collagen, osteopontin, and osteocalcin expression decreased in osteoblasts treated by osteoporotic T cell exosomes. In contrast, an increased expression of the mentioned genes was observed following non-osteoporotic T cell exosome treatment. Additionally, osteoblast alkaline phosphatase (ALP) activity treated with non-osteoporotic T cell exosomes increased. However, this activity decreased in another group. Our data demonstrated that T cell exosomes obtained from osteoporotic and non-osteoporotic individuals could alter the osteoblastic function and gene expression by affecting the genes essential for bone remodeling.

Immunomodulatory and clinical responses to zinc gluconate supplementation in patients with Behçet's disease: A double-blind, randomized placebo-controlled clinical trial.

BACKGROUND & AIMS: Toll-like receptor (TLR) 2 and 4 are involved in the pathogenesis of Behçet's disease (BD). The current study aimed to investigate the effect of zinc supplementation on TLR-2/4 expression and the clinical manifestations of BD. METHODS: In this double-blind placebo-controlled randomized clinical trial, 50 BD patients were randomly allocated into either zinc gluconate (30 mg/day) or placebo groups for 12 weeks. Before and after the intervention, the surface and mRNA expression level of TLR-2 and TLR-4 in the leukocytes, serum level of zinc and tumor necrosis factor-α (TNF-α), quality of life, anthropometric measures, and blood pressure of patients were collected. BD activity was studied using the nonocular Iranian Behçet's disease dynamic activity measure (IBDDAM), Behçet's disease current activity form (BDCAF), and total inflammatory activity index (TIAI) at the pre-and post-intervention phases. The effect sizes were compared between two groups using analysis of covariance. RESULTS: There were significant decrease in TLR-2 mRNA (P = 0.038) and protein expression (P = 0.034) and nonocular IBDDAM score (P = 0.046) in the zinc group compared to placebo at the endpoint. The serum level of zinc was increased in the zinc group (P < 0.001). Zinc supplementation significantly decreased the TLR-4 surface (P = 0.012) and mRNA expression (P = 0.028) within the group. However, this decrease was not significant compared to the placebo group. There was no significant difference between the two groups regarding the serum level of TNF-α, BDCAF, TIAI, quality of life, anthropometric measures, and blood pressure (P > 0.05). CONCLUSIONS: The present study revealed that zinc supplementation significantly improved nonocular IBDDAM score and TLR-2 expression in BD patients. GOV REGISTRATION NUMBER: NCT05098678.

Effects of N-acetylcysteine supplementation on disease activity, oxidative stress, and inflammatory and metabolic parameters in rheumatoid arthritis patients: a randomized double-blind placebo-controlled trial.

Considering the importance of inflammation and oxidative stress in the development of rheumatoid arthritis (RA) as well as anti-inflammatory and antioxidant features of N-acetylcysteine (NAC), this study was conducted to evaluate the effect of NAC supplementation on disease activity, oxidative stress, and inflammatory and metabolic parameters in RA patients. In a randomized double-masked placebo-controlled trial, 74 RA subjects were chosen and randomly divided into two groups to take 600 mg of NAC or placebo twice daily for 3 months. Before and after the study, disease activity was assessed via disease activity score-28 (DAS-28), and serum malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione peroxidase (GPX) activity, nitric oxide (NO), high-sensitivity C-reactive protein (hs-CRP), fasting blood sugar (FBS), lipid profile, and erythrocyte sedimentation rate (ESR) were measured. Seventy patients completed the trial. Compared to baseline, NAC significantly reduced morning stiffness (P < 0.001), DAS-28 (P < 0.001), ESR (P = 0.004), MDA (P < 0.001), NO (P < 0.001), hs-CRP (P = 0.006), FBS (P < 0.001), and low-density lipoprotein cholesterol (LDL-C) (P = 0.023) and significantly increased GPx activity (P = 0.015) and high-density lipoprotein cholesterol (HDL-C) level (P = 0.001). After treatment, remarkable differences were only seen between the two groups in serum NO (P = 0.003), FBS (P = 0.010), and HDL-C (P < 0.001) adjusted for baseline measures. There were no significant changes in morning stiffness, DAS-28, ESR, hs-CRP, MDA, TAC, GPx activity, triglyceride, total cholesterol, and LDL-C levels compared to the placebo group. In conclusion, NAC did not improve RA disease activity, but reduced NO and FBS and increased HDL-C levels. It appears that NAC should not be consumed as a replacement for routine medications prescribed in RA therapy, but it can be used as an adjunctive therapy.

Cigarette smoking and risk of palindromic rheumatism: A propensity score matching analysis.

Present study was conducted to investigate smoking status in palindromic rheumatism (PR) patients compared to healthy individuals as well as to assess the effect of smoking on clinical features and outcomes of PR. One hundred and forty-six patients with diagnosis of PR and 346 healthy controls were included in this study. Demographic, clinical, and laboratory characteristics and the smoking history of PR patients at the cohort entry were obtained from patients' records. Demographic and smoking history of the control group were obtained by direct interview. In order to reduce heterogeneity between the studied groups, propensity score matching (PSM) analyses was performed. Matching was achieved by considering age, gender, educational status, and marital status. After PSM, we carried out a multivariate analysis with PR as the main outcome variable, ever smoking as the main predictor variable and age, gender, educational status, and marital status as covariates. PSM resulted in 123 PR patients and 246 matched controls. Multivariate analysis did not show a significant increase in the risk of PR in ever smokers. Seventy-six patients were anti-citrullinated protein/peptide antibody positive (ACPA-positive). Multivariate logistic regression showed a significant increase in the risk of PR in ACPA-positive ever smokers. Except lower sustained remission rate in ever smokers, no significant differences were observed in clinical manifestations and outcomes of PR between ever and never smokers. In conclusion, smoking is a risk factor for ACPA-positive PR.

Profiling inflammatory cytokines following zinc supplementation: a systematic review and meta-analysis of controlled trials.

Chronic inflammation has been considered as the main cause of chronic diseases. Zn has anti-inflammatory effects by decreasing the expression of inflammatory markers. The present systematic review and meta-analysis study aims to evaluate the impact of Zn supplementation on inflammation. PubMed (Medline), Scopus, Web of Science, and Embase databases were searched up to 10 December 2020. Controlled trials which have investigated the effects of Zn supplementation on serum/plasma levels of inflammatory cytokines in subjects aged >15 years were included. A pooled meta-analysis was performed using a random effect model. Sensitivity analysis was performed to determine the robustness of the observed effect sizes. A total of twelve studies was included in meta-analysis. Zn could decrease IL-6 levels (standardised mean difference (SMD) = -0·76 pg/ml; 95 % CI -1·28, -0·24; P = 0·004). There was no significant change in TNF-α (SMD = 0·42 pg/ml; 95 % CI -0·31, 1·16; P = 0·257) and IL-2 levels (SMD = 1·64 pg/ml; 95 % CI -1·31, 4·59; P = 0·277) following Zn supplementation. However, Zn could increase IL-2 significantly after the deletion of one arm in sensitivity analysis (SMD = 2·96 pg/ml; 95 % CI 2·03, 3·88; P < 0·05). Conclusively, Zn supplementation can decrease the IL-6 level. Zn increased IL-2 level after the sensitivity analysis. Zn supplementation has not ameliorative effects on TNF-α.

Lack of association between six-minute walk distance and pulmonary artery pressure in patients with systemic sclerosis and cardiopulmonary symptoms.

The six-minute walk test (6MWT) is a non-invasive test used to assess cardiopulmonary performance. The aim of this study was to evaluate the performance of 6MWT in predicting pulmonary artery hypertension (PAH) and interstitial lung disease in patients with systemic sclerosis (SSc) and cardiopulmonary symptoms. Sixty-three patients with SSc who had dyspnea, cough, chest pain and syncope underwent 6MWT, high-resolution computed tomography (HRCT), spirometry, body plethysmography and single breath carbon monoxide diffusion measurement. There were no significant differences in mean 6MWD between patients with diffuse SSc compared with limited disease, patients with no parenchymal involvement compared with patients with parenchymal involvement <20% and≥20% in HRCT, and patients with PAP ≥25 mm Hg compared with patents with PAP <25 mm Hg. No significant relationship was found between 6MWD and age, mean PAP, forced expiratory volume, forced vital capacity and diffusing capacity of the lungs for carbon monoxide. The present study showed that in patients with SSc and cardiopulmonary symptoms, 6MVT does not help to predict PAH and parenchymal lung involvement.

Tuberculin skin test conversion in patients under treatment with anti-tumor necrotizing factor alpha agents.

BACKGROUND: Despite successful clinical outcomes of biologic medications in patients with chronic rheumatic diseases, some considerable adverse effects such as infections remain a major concern. Possibility of tuberculosis (TB) reactivation over treatment with anti-tumor necrotizing factor (TNF) alpha agents has necessitated a screening test before initiation of treatment. However, screening over the course of treatment is not recommended in those patients with negative baseline screening tests. This study aimed to evaluate the efficacy of tuberculin skin test (TST) before treatment in patients with chronic rheumatologic diseases who were indicated to receive anti-TNF-alpha therapy and the necessity of repeating this test over the course of treatment. METHODS: In this prospective study, patients with chronic rheumatologic diseases receiving anti-TNF-alpha agents were studied in a two-year period. TST was performed before treatment and those with positive results were excluded from the study. Thereafter, treatment with anti-TNF-alpha agents was initiated with the indicated dose. TST was repeated before administration of biologic treatment until TST became positive or 16 weeks after the initiation of treatment with anti-TNF-alpha. RESULTS: A total of 51 cases were studied, of whom one patient (1.9%) was excluded due to positive TST before treatment. All participants received infliximab and the TST test became positive in one patient (2%) 2 weeks after receiving the first dose. Also, the results of further tests at weeks 6, 10, and 14 were all negative for the remaining patients. CONCLUSION: Due to the possibility of TST conversion after administration of anti-TNF-alpha therapy, it is important to consider TB monitoring in patients under treatment with these agents using available methods such as TST.

The methylation status of TNF-α and SOCS3 promoters and the regulation of these gene expressions in patients with Behçet's disease.

Introduction: The aim of this study was to evaluate the methylation status of TNF-α and SOCS3 promoters in patients with BD and compare them with a healthy group.Method: This was a case-control study, in which 47 subjects with BD and 61 individuals as the control participated. Blood samples were collected from all the participants. Then, PBMCs were isolated using the Ficoll method and methylation of considered sites was investigated using the qMS-PCR technique after DNA extraction by the rapid genomic DNA extraction method and its analysis with Nano-drop.Results: The methylation and expression of TNF-α showed that the methylation level significantly declined in the patient in comparison with the healthy (p < 0.05). Moreover, the results on the mean expression showed that it significantly increased in the patient group, as compared with the healthy group (p < 0.05). In addition, the expression of the SOCS3 gene was not significantly different between the patients and healthy subjects while the level of SOCS3 methylation was significantly higher in the patient group than that in the healthy group (p < 0.05).Discussion: The present study revealed that the gene expression of TNF-alpha increased in BD patients, suggesting that TNF-alpha likely has a role in the pathogenesis of BD.

Effect of Nigella sativa oil extracts on inflammatory and oxidative stress markers in Behcet's disease: A randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVE: Behcet's disease (BD) is a chronic inflammatory disorder characterized by recurrent oral and genital aphthous ulcers, uveitis and skin lesions. Oxidative stress and inflammation have important role in the pathogenesis of BD. The aim of this study was to assess the effect of Nigella sativa (NS) oil administration on malondialdehyde (MDA), total anti-oxidant capacity (TAC), tumor necrosis factor-α (TNF-α), IL-10 and high sensitivity C-reactive protein (hs- CRP) levels in patients with BD. MATERIALS AND METHODS: In this randomized, double-blind and placebo-controlled clinical trial, 96 BD patients were randomly assigned to NS or placebo groups. Study groups received 1000 mg/day NS oil and placebo soft gels for 8 weeks. Serum levels of TNF-α, IL-10, hs-CRP, MDA and TAC were measured before and after treatment. RESULTS: Eighty-nine individuals completed the study. Significant decreases in the serum levels of MDA and increases in the serum levels of TAC were found in the NS group. However, differences in the changes of MDA and TAC in the NS and placebo groups were not significant. Pre- and post-intervention changes of TNF-α, IL-10 and hs-CRP levels in the NS group were non-significant. CONCLUSION: NS 1000 mg per day is probably not effective in reducing the inflammatory and oxidative markers in BD.

Promoter methylation of Bax and Bcl2 genes and their expression in patients with Behcet's disease.

BCL2 and BAX genes are a group of signalling inducer and inhibitor genes playing a key role in the process of cellular physiological death (apoptosis). These genes, through the JAK/STAT signalling pathway, affect different cytokines on cell function and subsequently lead to the pathophysiology of diseases, especially autoimmune diseases. In addition, altering the methylation of genes can affect their expression. Since the aetiology and pathology of Behcet's disease is not fully understood, the aim of this study was to determine the methylation pattern of BCL2 and BAX genes in patients with Behcet's disease and compare it with those of control group. This was a case-control study on 51 patients with Behcet and 61 control subjects. Blood samples were received from all subjects. Subsequently, the peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll method and the methylation of the sites was investigated using quantitative methylation specific PCR (qMS-PCR) technique after extraction of DNA by salting out method and its examination with Nano drop. The results of methylation and expression of Bax gene suggest that the methylation level in the patient group significantly increased compared to the healthy individuals (p-value < .05). Furthermore, the results related to Bax gene expression revealed that the mean of gene expression in the patient group has decreased compared to the healthy group, and this decrease was statistically significant (p-value < .05). The rate of expression and methylation of Bcl2 did not indicate any change in the two patient and healthy groups. Given the results of this study, it can be guessed that perhaps DNA methylation is involved in certain conditions of the disease and it may result in regulation of the expression of the involved genes such as Bax gene, in the pathogenesis of the disease.

Methylation status of interleukin-6 gene promoter in patients with Behçet's disease.

BACKGROUND: IL-6 mRNA expression is significantly high in many autoimmune diseases such as Behçet's disease; this is often related with more aggressive phenotypes. Nevertheless, the essential molecular process for its high expression has not been completely realized. The aim of this study was undertaken to estimate the gene copy number variation and promoter methylation to IL-6's high expression. METHODS: This study was performed on 51 patients and 61 healthy controls. Initially, DNA and RNA were extracted from all specimens. Promoter methylation levels of IL-6 were evaluated by MeDIP-qPCR technique. Also, IL-6 gene expression was measured by Real-time PCR. After that, we evaluated the relationship between gene expression and methylation, as well as their relationship with clinical specification. RESULTS: As we expected, the expression level of IL-6 gene increased significantly in the patient group compared to the healthy subjects. Also, the relative promoter methylation level of the IL-6 mRNA was significantly lower in patient group compared to healthy group (p<0.001). DISCUSSION: We disclosed that the promoter hypomethylation may be considered as one of the main defects for IL-6 mRNA high expression in patients with Behçet's disease.

The expression and methylation status of vitamin D receptor gene in Behcet's disease.

INTRODUCTION: Vitamin D has important roles as a natural immune modulator via regulating the expression of genes which have been implicated in the pathophysiology of autoimmune diseases. Vitamin D function and its deficiency have been linked to a wide range of metabolic disorders including disorders of calcium metabolism, malignant, cardiovascular, infectious, neuromuscular, and inflammatory diseases. Environmental factors, genetic factors, and epigenetic changes contribute to Behcet's disease (BD) development. The aim of our study was to analyze the expression level and methylation status of the vitamin D receptor (VDR) gene promoter in the peripheral blood mononuclear cells (PBMCs) of patients with BD. METHODS: In a case-control study, 48 Iranian Azeri patients with BD and 60 age-, sex- and ethnically-matched healthy controls were included. Venous blood samples were collected and PBMCs were isolated by Ficoll protocol. The DNA and RNA were subsequently extracted. Promoter methylation levels were evaluated by MeDIP-quantitative polymerase chain reaction (qPCR). The expression of VDR was evaluated by real-time PCR. RESULTS: The results of quantitative real-time PCR analysis showed that the level of VDR expression in patients with BD was significantly lower than the control group (P = .013). There was no significant difference in the level of DNA methylation in the BD and control groups (P > .05). As the results show, the expression level of VDR gene was significantly different between female and male in the patient group (P = .001). VDR gene expression was significantly higher in subjects with phlebitis. No correlation was observed between VDR gene expression rate and BD activity. CONCLUSION: VDR gene expression decreased in patients with BD. However, there is no suggestion evidence that the expression level of VDR is regulated by a unique DNA methylation mechanism. No correlation exists between VDR gene expression and BD activity.

The molecular and clinical evidence of vitamin D signaling as a modulator of the immune system: Role in Behçet's disease.

Various tissues and cell types are the targets of vitamin D. However, the major targets of vitamin D in the immune system are monocytes/macrophages, dendritic cells (DCs), as well as B and T cells. Vitamin D plays an important role in the immune system modulation via regulating the expression of genes that generate pro-inflammatory mediators and inhibiting the proliferation of pro-inflammatory cells, both of which have been implicated in the pathophysiology of the inflammatory diseases. Recent studies have revealed the important relations between vitamin D and Behçet's disease (BD). Vitamin D function and its deficiency have been linked to a wide range of metabolic disorders including malignant, cardiovascular, infectious, neuromuscular, and autoimmune diseases. Here, we provide a brief analysis of the recent literature regarding immune-regulatory effects as well as clinical evidence of vitamin D influence on the molecular level in BD.