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Common variable immunodeficiency (CVID) is a primary immunodeficiency disease with a heterogeneous genetic background. Lipopolysaccharide-responsive beige-like anchor (LRBA), as well as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), have important regulatory roles in the immune responses. Here, we have investigated the expression of LRBA and CTLA-4 proteins in CVID patients with at least one presentation of early-onset occurrence, autoimmunity, or enteropathy. In this study, 20 newly diagnosed CVID patients without infection only phenotype, and ten healthy individuals were enrolled. The expressions of LRBA and CTLA-4 proteins were assessed by western blotting and flow cytometry, respectively. The patients were divided into two groups of autoimmunity-positive (11 cases) and autoimmunity-negative (9 patients). LRBA and CTLA-4 expressions were significantly lower in autoimmune-positive patients than in healthy individuals (

Endometriosis, an inflammatory disease, is assumed to be associated with an increased production of growth-related cytokines. Based on the emerging immunomodulatory role of vitamin D3 in different inflammatory conditions, this study aimed to examine its modulatory effect on the expression levels of the genes for platelet-derived growth factor-B (PDGFB), monocyte/macrophage-derived growth factor (MDGF, also known as PPBP) and epidermal growth factor (EGF) in peritoneal fluid mononuclear cells (PFMC) in women with and without endometriosis.PFMC from 10 women with endometriosis and 10 control participants were treated with vitamin D3.The gene expression levels of PDGFB, MDGF and EGF were measured 6, 24 and 48 h following vitamin D3 administration using real-time PCR.Gene expression levels of EGF and PDGFB were higher in the PFMC of women with endometriosis than the control group (P = 0.006, P 0.001, respectively). Although MDGF expression showed an increase in the endometriosis group compared with non-endometriotic controls, no significant difference was found. Vitamin D3 significantly decreased EGF expression at 6, 24 and 48 h (P 0.001, P 0.001 and P = 0.007, respectively), MDGF at 24 and 48 h (P 0.001 and P = 0.009, respectively) and PDGFB at 6 h (P = 0.047) in the endometriosis group. Vitamin D3 treatment had no significant effect on expression of the genes in the PFMC of non-endometriotic women.The study concluded that PDGFB and EGF gene expression increases in endometriosis, and vitamin D3 could markedly decrease this expression, suggesting its therapeutic potential in endometriosis.

Background Studies trying to find the association between vitamin D status and metabolic syndrome (MetS) have led to inconsistent results, and community-based data for individuals living in the Middle East are limited. Objectives To find out if MetS and its components are associated with vitamin D status among female teachers residing in Yazd city during winter 2015. Materials and methods A total of 276 female teachers (case group, n = 124 and control group, n = 152) aged 20–60 years were included. Weight, height, waist circumference, blood pressure, daily energy intake, physical activity, serum 25 hydroxy vitamin D (25(OH)D3), fasting blood glucose, triglycerides and high-density lipoprotein cholesterol (HDL-C) levels were assessed. Logistic regression was used to examine the odds ratio of MetS according to vitamin D status. Results Mean serum 25(OH)D3 was 32.79 ± 18.62 ng/ml and 33.73 ± 20.20, in females with and without MetS, respectively (P > 0.142). Compared to those with 25(OH)D3of 0.05). Conclusion Although several studies have claimed the association between vitamin D status and MetS, we could not find a similar connection in a sample of Iranian female teachers. Prospective studies are needed to determine the possible effect of vitamin D in the development of MetS, particularly in the Yazd province.

Multiple sclerosis (MS) is described as an immune disorder with inflammation and neurodegeneration. Relapsing-remitting MS (RRMS) is one of the most common types of MS. The diagnostic manner for this disorder typically includes the usage of magnetic resonance imaging (MRI); however, this is not always a very precise diagnostic method. Identification of molecular biomarkers in RRMS body fluids samples compared to healthy subjects can be useful to indicate the normal and pathogenic biological processes or pharmacological responses to drug interaction. In this regard, this study evaluated different miRNAs in isolated peripheral blood mononuclear cells (PBMCs) of RRMS compared to controls and their correlations with altered T regulatory type 1 (Tr1) cells, osteopontin (OPN), and interleukin 10 (IL-10) levels. The frequency of Tr1 cells was measured using flow cytometry. Also, the expressions of different miRNAs were evaluated via quantitative real-time polymerase chain reaction (RT-qPCR) and plasma levels of IL-10 and OPN were tested by enzyme-linked immunosorbent assay (ELISA). The obtained results showed the Tr1 cells' frequency, Let7c-5p, and miR-299-5p levels decreased in RRMS patients to about 59%, 0.69%, and 20% of HCs, respectively, (P 0.05). The miR-106a-5p levels increased about 7.5-fold in RRMS patients in comparison to HCs (P 0.05). Moreover, the results showed that there was an increased negative association between Tr1 frequency and plasma-OPN levels in RRMS patients in comparison to HCs and also, we found a moderate positive correlation between plasma-IL-10 and miR-299-5p expression of RRMS patients. Overall, it may be possible to use these biomarkers to improve the diagnostic process. These biomarkers may also be considered for clinical and therapeutic studies in the future.

Background Preeclampsia (PE) is one of the most serious disorders of human pregnancy with a high rate of mortality for the fetus and mother. Several etiological factors are involved in the onset of this disease. Upregulation of IL-27 has been reported in placental tissue recovered from preeclamptic women, but the role of IL-27 has not yet been investigated in PE. The aim of the study was to investigate the association of IL-27 rs153109 and rs17855750 gene polymorphisms with PE; also, protein levels and susceptibility and severity of PE in Iranian women were evaluated. Methods This case-control study was performed on 199 PE patients and 228 healthy women as the control group. IL-27 rs153109 and rs17855750 SNPs were genotyped using a PCR-RFLP method. Moreover, the levels of IL-27 were determined in 40 PE and 45 healthy women using ELISA method. Results Statistical analysis indicated that there were no differences in genotype, allele and genotype combination frequencies in the SNPs between cases and controls. The plasma level of IL-27 was elevated in the mild form of the disease compared with controls (p-value: 0.006). Conclusions The effect of IL-27 in preeclampsia is not due to the studied cytokine polymorphisms, but the level of IL-27 might be associated with the severity of preeclampsia in Iranian women.

Background: Recurrent pregnancy loss (RPL) refers to the incidence of two or more abortions before the first half of pregnancy. Oxidative stress has been hypothesized to play a central role in RPL. Objective: To investigate the relationship between Q192R and L55M polymorphisms of PON1 as antioxidant enzyme and the risk of RPL. Materials and Methods: In this case–control study, 110 women with RPL (case) and 110 healthy fertile women (control) referred to the Research and Clinical Center for Infertility, Shiraz, Iran were enrolled. Genomic DNA was extracted from the peripheral blood in all participants. Polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism method. Results: Statistical analysis of Q192R polymorphism showed a significant difference for the RR genotype between the case and control group (OR = 11, CI = 1.39–86.87, p = 0.005) but none for the QR and QQ genotypes. No significant association was observed between the R and Q allelic frequency in the RPL participants compared to the control group (p = 0.53). Also, statistical analysis of the L55M polymorphism for MM genotype in the case group compared with the control group showed a significant difference (OR = 3.59, CI = 0.97–13.30, p = 0.042), but none for the LM and LL genotypes. Conclusion: The findings showed a significant correlation between the Q192R polymorphisms and the L55M PON1 enzyme and RPL in this study population. Key words: Pregnancy, Abortion, PON1, Polymorphism, Recurrent pregnancy loss.

Condition Based Maintenance (CBM) using inspection data is one of the available maintenance approaches for power system equipment. In Inspection Based Maintenance (IBM) as a specific type of CBM, decisions about the time and type of the maintenance tasks are made after determining the deterioration condition of the equipment. In this paper, an IBM model is proposed for yearlong transmission equipment maintenance scheduling. In order to quantify the effect of the inspection and maintenance tasks, the probability distribution of the deterioration condition is calculated using the transition probability matrix of the Markov process. The problem of system level maintenance scheduling is formulated with binary variables as weekly inspection time during the year. Inspection time of equipment is optimized by minimizing the total cost, including inspection, maintenance, redispatch and failure costs while network security constraints are considered. The proposed model is implemented for the maintenance of transformers and transmission lines in IEEE-RTS and IEEE 57-bus test systems.

Background Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease characterized by the production of autoantibodies and activated immune cells against self-antigens. Probiotics are known to possess anti-inflammatory and modulatory effects on the immune responses. In this study, we evaluated the effect of probiotics Lactobacillus rhamnosus and Lactobacillus delbrueckii on the expression levels of miR-155 and miR-181a in the PBMCs of SLE patients. Methods A total of 20 newly diagnosed SLE patients and 20 healthy controls were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood and treated with probiotics Lactobacillus rhamnosus (107 Bac/mL) and Lactobacillus delbrueckii (105 Bac/mL), and cultured in RPMI-1640 for 48 h. Afterwards, total RNA containing micro-RNAs were extracted. cDNA was synthesized for miRNAs and gene expression of miR-181a and miR-155 was analyzed using quantitative real-time PCR method. Results Higher expression levels of miR-181a and miR-155 were found in SLE patients compared with healthy controls. Treatment of PBMCs with L. rhamnosus, L. delbrueckii and combination of these probiotics downregulated the expression of miR-181a and miR-155 in treated cells compared with untreated cells. Conclusions L. rhamnosus and L. delbrueckii modulate the expression of miR-181a and miR-155 in SLE patients and might be beneficial in the management of SLE patients.

Aims B cells can promote or inhibit immune responses against breast cancer. We investigated changes in the frequency of B cells with stimulatory or regulatory capacity in breast tumor draining lymph nodes during cancer progression. Main methods We isolated mononuclear cells from fresh axillary lymph nodes (LNs) of 44 patients with breast cancer and stained lymphocytes with antibodies against CD19, CD80, CD86, CD39 and CD73. To assess programmed death-1 (PD-1) and PD-ligand 1 (PD-L1) expression, lymphocytes were briefly stimulated, stained for CD19, PD-1 and PD-L1, and examined with flow cytometry. Key findings The frequency of CD80+ B cells was higher in nonmetastatic lymph nodes, while the percentage of CD86+ B cells showed a positive relationship with higher tumor grade and higher numbers of involved LNs. A small proportion of unstimulated B cells expressed PD-1 or PD-L1 but these molecules were rapidly upregulated on B cells following activation. The frequency of stimulated PD-L1+ B cells showed an inverse association with estrogen and progesterone receptor expression and a nonsignificant positive association with tumor grade. In addition, the percentage of unstimulated PD-1+ B cells was higher in patients with higher-grade tumors. CD73 expression on B cells was associated with lower numbers of involved LNs, and the frequency of CD39+ B cells was higher in patients with larger tumors. Significance CD86+, CD39+, PD-1+ and PD-L1+ B cells showed associations with poor prognostic factors, therefore their potential role in the suppression of the immune responses against breast cancer should be evaluated in greater detail.

Regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC) are the two important and interactive immunosuppressive components of the tumor microenvironment that hamper anti-tumor immune responses. Therefore, targeting these two populations together might be beneficial for overcoming immune suppression in the tumor microenvironment. We have recently shown that prophylactic Foxp3 DNA/recombinant protein vaccine (Foxp3 vaccine) promotes immunity against Treg in tumor-free conditions. In the present study, we investigated the immune modulatory effects of a prophylactic regimen of the redesigned Foxp3 vaccine in the B16F10 melanoma model. Our results indicate that Foxp3 vaccination continuously reduces Treg population in both the tumor site and the spleen. Surprisingly, Treg reduction was associated with a significant decrease in the frequency of MDSC, both in the spleen and in the tumor environment. Furthermore, Foxp3 vaccination resulted in a significant reduction of arginase-1(Arg-1)-induced nitric oxide synthase (iNOS), reactive oxygen species (ROS) and suppressed MDSC activity. Moreover, this concurrent depletion restored production of inflammatory cytokine IFN-γ and enhanced tumor-specific CTL response, which subsequently resulted in the reduction of tumor growth and the improved survival rate of vaccinated mice. In conclusion, our results revealed that Foxp3 vaccine promotes an immune response against tumor by targeting both Treg and MDSC, which could be exploited as a potential immunotherapy approach.

Introduction Previous studies approved the important roles of CD68, as scavenger receptors, in Alzheimer's disease (AD). The aim of this study was to evaluate the effect of treatment with anti-psychotic drugs and vitamin B12 on the expression levels of CD68 in monocytes of psychotic AD patients. Material and methods Expression of CD68 on the monocytes was evaluated in the following groups: 1. age and sex matched healthy controls (Group 1), 2. non-psychotic AD patients (Group 2), 3. psychotic AD patients (Group 3), 4. psychotic AD patients treated with Risperidone (Group 4), 5. psychotic AD patients treated with Risperidone plus vitamin B12 (Group 5), 6. psychotic AD patients treated with Quetiapine (Group 6), psychotic AD patients treated with Quetiapine plus vitamin B12 (Group 7). The expression of CD68 has been performed using flow cytometry technique. Results The results showed that CD68 levels were significantly increased in AD patients in comparison to healthy controls and in psychotic AD patients in comparison to non-psychotic AD patients. Treatment with anti-psychotic drugs decreased the expression of CD68. Expression of CD68 has a positive correlation with pain, dementia and mental disorders symptoms in psychotic AD patients. Discussion CD68 may play key roles in the pathogenesis of AD and its complications may be via induction of inflammation. Therefore, it may be concluded that CD68 may be considered as a risk factor for development of AD and also psychotic symptoms in the patients.

Inflammatory cytokine, interleukin-6 (IL-6), plays an important role in the pathogenesis of cardiac hypertrophy. Recent studies have documented that resveratrol exhibits cardioprotective effects. The present study attempts to explore whether resveratrol suppreses IL-6 in hypertrophied H9c2 cardiomyoblasts through histone deacetylase, sirtuin 1 (SIRT1). To induce hypertrophy, the cells were incubated with angiotensin II (Ang II). Treatment groups were treated with different doses (1, 10, 25, 50, 75, and 100 μM) of resveratrol (R). Cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell size was determined using crystal violet staining. Gene expression was assessed by real-time polymerase chain reaction technique. Enzyme-linked immunosorbent assay was used to measure IL-6 concentration. The results showed that cell area and ANP messenger RNA (mRNA) levels decreased significantly in R25+Ang, R50+Ang, and R100+Ang groups, as compared with Ang group. Therefore, 10, 20, 30, 40, and 50 μM of resveratrol were used to to evaluate its anti-inflammatory effects. The results revealed that Ang II upregulated IL-6 at both mRNA and protein levels (p < .001 vs. normal) and resveratrol (50 μM) decreased IL-6 mRNA (p < .01) and protein (p < .05) significantly in comparison to Ang group. However, in groups in which the cells were pretreated with SIRT1 inhibitor, EX-527, the response of resveratrol was partially reversed. Transcription levels of IL-6 receptor components (gp130 and gp80) did not change significantly among the experimental groups. The current data suggests that resveratrol protects H9c2 cells against Ang II-induced hypertrophy by suppression of IL-6 through SIRT1 activation.

Liver fibrosis is an inflammatory and fibrogenic process that occurs following chronic liver damage. TGFβ1 is the key inducer of fibrosis. MiR-21 and miR-122 are two miRNAs that their expression changes during fibrosis. In the present study, we investigate the effects of curcumin, quercetin, and atorvastatin on the expression levels of miR-21 and miR-122 and evaluated their correlation with TGFβ1 expression in bile duct ligation (BDL)-induced fibrotic rats.Thirty two adult male Wistar rats were divided into 8 groups (n = 8 for each): Sham, Sham + curcumin (100 mg/kg/day), Sham + quercetin (30 mg/kg/day), Sham + atorvastatin (15 mg/kg/day), BDL, BDL + curcumin, BDL + quercetin, BDL + atorvastatin and treated for four weeks via oral gavage. The expression of miR-21, miR-122, and TGFβ1 was evaluated via RT-qPCR.The expression levels of TGFβ1 and miR-21 were significantly increased in the BDL group compared to the Sham group (P 0.05), but the expression of miR-122 was significantly decreased in the BDL group compared to the Sham group (P 0.05). Curcumin, quercetin, and atorvastatin treatment lead to down-regulation of miR-21 and TGFβ1 and up-regulation of miR-122 in the BDL groups. There was no significant difference between these drugs in altering gene expression and all had the same effects. Moreover, a direct significant correlation was observed between mir-21 and TGFβ1 and an inverse significant correlation between mir-122 and TGFβ1 expression.In summary, targeting these molecular pathways may partially prevent the progression of liver fibrosis.

Background:Studies on the association between a priori dietary patterns and serum highly sensitive C-reactive protein (hs-CRP) have led to inconsistent results, and we are not aware of any study on interleukin 17A (IL-17A) as an inflammatory marker associated with autoimmune diseases.Objective:The present study aimed to investigate the association between Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean dietary patterns with circulating hs-CRP and IL-17A levels.Methods:In this cross-sectional study, female teachers (aged 20-50 years) who lived in Yazd, Iran, were randomly selected from elementary, guidance, and high schools from September 2015 to February 2016. Anthropometric data, as well as general information and dietary food intakes, were gathered, and each participant gave 1 blood sample. Participants were categorized into tertiles based on the DASH and the Mediterranean diet calculated scores. The associations between the dietary patterns and serum hs-CRP and IL-17A levels were assessed in the crude and multivariable models. In total, 320 female teachers aged 40.38 (8.08) years were included.Results:The DASH diet was associated with lower serum hs-CRP levels in the crude ( P = .05) and the fully adjusted models ( P = .02), while it was not significantly associated with IL-17A levels. The participants with the highest adherence to the Mediterranean diet had significantly lower circulating IL-17A levels ( P = .04) even controlling for all confounders ( P = .02); however, there was not a significant relationship between this diet and hs-CRP levels.Conclusions:The DASH and the Mediterranean dietary patterns might be differently associated with inflammatory markers. Further prospective studies are recommended to confirm our results.

Th17/IL-23 axis is an important pro-inflammatory pathway in atherosclerosis. IL-23 receptor (IL-23R) pathway has an important role in T-helper cells 17 (Th17) differentiation and survival. We compared normal subjects and patients with atherosclerosis in terms of the R381Q variant of the IL-23R gene as a functional single-nucleotide polymorphism (SNP). This case-control study recruited 200 patients who presented with cardiovascular symptoms to Afshar Hospital, Yazd, Iran. The participants were allocated to five groups based on angiographic results. The severity of the disease was determined according to the numbers of involved vessels. Patients with normal coronary arteries, minimal coronary artery involvement, one involved vessel, two involved vessels and three-vessel disease were allocated to groups I-V, respectively. DNA was extracted from whole blood samples by the salting-out method. Genotyping was performed by polymerase chain reaction followed by restriction fragment length polymorphism assay and multinomial logistic regression for analyses The presence of SNP A>G rs11209026 of IL-23 receptor gene was significantly associated with disease severity (P = 0.008). The frequencies of the heterozygous (AG) genotype in the control group and subjects with minimal involvement, and patients with one-, two-, and three-vessel disease were 22.5%, 12.5%, 10%, 10.24% and 4.8%, respectively. Our results indicated an association between the rs11209026 G>A polymorphism of the IL-23 receptor gene and the risk of atherosclerosis. This genetic variant may in fact cause protection against atherosclerosis progression. However, further studies on gene polymorphism and cell expression are required to clarify the mechanisms involved in the pathogenesis of atherosclerosis.

Recurrent spontaneous abortion (RSA) is defined as three or more consecutive spontaneous abortions before the 20th week of gestation. The purpose of the present study was to investigate the association between a functional single nucleotide polymorphism (SNP) in the interleukin (IL)-23 receptor gene (IL-23R; rs11209026, 1142 G wild type → A reduced function, Arg381Gln, R381Q) and RSA. For the study, 200 RSA patients (confirmed using established diagnostic criteria) and 200 normal individuals in fertility and infertility centers in the cities of Yazd and Isfahan were recruited during a period from 2012-2013. Using PCR-RFLP, the R381Q variant was screened for in the IL-23R gene of the patients and controls. The results indicated there were significant differences in the frequency of this genetic variant in the patients versus the healthy controls, i.e. 2% and 7.5%, respectively (p value = 0.01; odds ratio = 0.25; CI = 95%). No significant difference was found for the G allelic frequency in patients with RSA and in the control group (p = 0.60). The A allelic frequency was significantly different between the two groups (p = 0.01). Based on these findings, it is concluded that the frequency of single nucleotide polymorphism in the IL-23 receptor (R381Q) in patients with recurrent spontaneous abortion (RSA) is less than that found in normal control women.

Programmed death-1 (PD-1) negatively regulates the immune response. The aims of this study were to assess the association of two single nucleotide polymorphisms in the PD-1 gene, PD-1.5 (+7785 C/T-rs2227981) and PD-1.3 (+7146 G/A- rs11568821), with benign and malignant brain tumors. Patients with brain tumors (96 patients with benign and 56 with malignant brain tumors) and 150 healthy control individuals were included. PCR-RFLP was performed for genotyping. It was revealed that the genotype and allele frequencies of PD-1.5 C/T polymorphism were significantly different between all brain tumor patients and the control group. The frequencies of the CT genotype and T allele were higher in brain tumor patients. In contrast, the frequency of PD-1.3 G/A genotypes and alleles showed no significant difference between all brain tumor patients and controls. Patients were then divided into malignant and benign groups. The results revealed a significant difference in both patients groups compared with the controls only at PD-1.5 C/T position. Arlequin analysis showed the GC haplotype was the most frequent haplotype in the whole group of patients and controls, and the GT haplotype was significantly different between patient and control groups. In conclusion, we demonstrate that PD-1.5 C/T polymorphism, but not PD-1.3 G/A, is associated with brain tumors in Iranian patients.

AIM To examine the relationship between dietary patterns and inflammatory markers including serum high sensitivity C-reactive protein (hs-CRP) and interleukin 17A (IL-17A) in females. METHODS In the present cross-sectional study in female teachers living in Yazd, central Iran, data on anthropometric measurements and general information were gathered. A food frequency questionnaire was completed by participants and then, subjects were invited to give blood samples. Major dietary patterns were derived using principal component analysis and serum inflammatory markers were compared according to quintiles of dietary patterns scores. RESULTS In total, 320 subjects aged 40.38 ± 8.08 years were included. Three dietary patterns were derived: (i) 'traditional' with a high intake of poultry, salt, eggs, other vegetables and red meat; (ii) 'vegetables and fruits' with a higher intake of tomatoes, yoghurt drinks, green leafy vegetables, dried fruits, fruits, other vegetables and organ meats and (iii) 'dairy and saturated fat' with a high loading of high-fat dairy products, butter, low-fat dairy, margarine, eggs, other vegetables and green leafy vegetables. Participants in the highest quintile of the 'vegetables and fruits' dietary pattern had significantly lower serum hs-CRP levels compared to those in the lowest quintile (3.6 ± 0.4 mg/L vs 2.6 ± 0.4 mg/L, respectively; P

Recurrent spontaneous abortion (RSA) is defined as three or more consecutive abortions before the 20th week of gestation. There is increasing evidence to support an immunological mechanism for the occurrence of RSA. The purpose of our study was to examine whether single-nucleotide polymorphisms (SNPs) of the interleukin-4 receptor gene IL4R influence susceptibility to, recurrent spontaneous abortion.This is a case-control study. We recruited 200 patients with RSA (case group) using established diagnostic criteria and 200, normal individuals (control group) at the fertility and infertility center in Yazd city and Isfahan city during 2012 to 2013. We screened the I50V variant in IL-4R in patients and controls by PCR-RFLF method, and we performed an association analysis between I50V variant and RSA.the data was analyzed by spss 16 software using Chi-square test.No differences in the genotype and allele frequencies of the I50V SNPs were identified between patients with RSA and healthy controls.The frequency of SNP in IL-4 receptor (I50V) in patients with recurrent spontaneous abortion did not differ significantly compared with the control group. Analysis of IL4R SNP haplotypes or complex alleles suggested no dominant protection in patients with RSA.

Interleukin-23 (IL-23) is a regulator of cellular immune responses involved in controlling infection and autoimmune diseases. Strong evidence has shown that IL-23 plays a role in the maintenance of immune responses by influencing the proliferation and survival of IL-17-producing T-helper (TH)-17 cells. The critical role of the IL-23/TH17 axis in immune-mediated diseases has emerged from different studies. It has also been seen that polymorphisms in the IL-23 receptor (IL-23R) gene might influence IL-23 responses. Interestingly, a functional single nucleotide polymorphism (SNP) in the IL-23 receptor gene (IL-23R; rs11209026, 1142 G wild-type A reduced function, Arg381Gln, R381Q) seems to confer a measure of protection against development of inflammatory bowel disease (IBD; Crohn's disease, ulcerative colitis), ankylosing spondylitis, rheumatoid arthritis, psoriasis, thyroiditis, recurrent spontaneous abortion and asthma, suggesting that a perturbation in the IL-23 signaling pathway is likely to be relevant to the pathophysiology of these diseases. The aim of this review was to provide an evaluation of what is currently known about the protective role of R381Q variant in IL-23R gene in immune-based diseases.

Human leukocyte antigen (HLA)-G is involved in immunoregulatory processes and particularly in pathogenesis of inflammatory disorders such as recurrent spontaneous abortions (RSA). The purpose of the current study was to examine whether two single nucleotide polymorphisms (SNPs) of HLA-G gene (rs1736936 and HLA-G*0105N) influence susceptibility to recurrent spontaneous abortion. Genomic DNA from 117 RSA patients and 117 normal fertile control individuals was isolated using the salted out method. The two single nucleotide polymorphisms in HLA-G gene were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Differences between the two groups were analyzed by SPSS19 software using Chi-square test. The results revealed a significant increase in HLA-G*0105N allele in the proportion of whole group of RSA women compared with fertile controls (P value = 0.015), OR (95 % CI) = 2.054 (1.798-2.347), as well as an absence of homozygosity for HLA-G*0105N in the study population. No significant difference was observed between the RSA and the fertile groups in terms of alleles and genotypes frequency of rs1736936 (P value = 0.323), OR (95 CI %) = 1.056 (0.844-1.319). The presented data suggest that the investigated HLA-G*0105N allele is potentially associated with RSA through linkage disequilibrium with other genetic elements. Meanwhile, the rs1736936 SNP do not predispose to RSA in the study population.

HLA-G is supposed to play a pivotal role in tolerance of the semi-allogeneic graft in pregnancy by inhibiting the cytotoxic functions of T and NK cells. A 14-bp insertion and/or deletion polymorphism in exon-8 has a possible role in HLA-G expression. The present study analyzed the 14-bp insertion/deletion polymorphism in normal pregnancy and recurrent miscarriage patients in order to discover a possible correlation between the 14-bp polymorphism and recurrent miscarriage (RM). In this study, genomic DNA from 200 RM patients and 200 normal fertile control individuals using the routine salting out method were isolated. Exon-8 of HLA-G gene of the two groups were amplified using polymerase chain reaction and analyzed by electrophoresis on 10% non-denaturing polyacrylamide gel electrophoresis containing ethidium bromide and visualized under ultraviolet light. HLA-G allele frequencies and genotypes in RM women and the fertile control group were compared using a Chi-square test. The results showed that there was a difference in allelic frequencies of 14-bp insertion polymorphism between fertile controls and RM patients; the frequency of +14 bp/-14 bp heterozygotes was significantly higher in RM patients as compared with fertile controls. Furthermore, the frequency of +14-bp insertion allele was significantly higher in those with RM as compared with normal fertile controls. From the findings here, it was concluded that a 14-bp insertion/deletion polymorphism in exon 8 could play a possible role in recurrent miscarriages. These results might ultimately be of significance for clinicians and those involved in understanding infertility and RM.

There is ample evidence in favor of various immunosuppressive mechanisms that weaken antitumor immune responses and affect currently used immunotherapies. Induction of regulatory T cells (Treg) and secretion of indoleamine 2,3-dioxygenase (IDO) by tumor tissue are considered as two main mechanisms of tumor immune escape. However, little is known about the contribution of these mechanisms on the modulation of dendritic cell vaccine-mediated antitumor response. To address this concern, we assessed Treg's infiltration and the expression of Foxp3 and IDO genes in tumor microenvironment following dendritic cell-based antitumor immunotherapy of mice in different protocols of prophylactic, concurrent, and therapeutic vaccination. According to cytotoxicity assay, the vaccinated mice exposed efficient induction of splenic CTLs in all groups. However, only the mice immunized in prophylactic regimen significantly retarded the growth of tumor cells. Interestingly, the Treg content of tumor samples and transcriptional level of both Foxp3 and IDO genes were reduced in this group, while animals that received the vaccine in concurrent and therapeutic protocols showed increase in tumor-infiltrating Tregs and mRNA levels of Foxp3 and IDO. Accordingly, higher expression of these genes resulted in more inhibition of antitumor response. Our findings indicate that tumor progression may enhance the immunoregulatory response and hence emphasize to the effectiveness of vaccination in early stages of tumor growth for avoiding induction of such regulatory responses.

Background: Human leukocyte antigen-E (HLA-E)is a non-classical major histocompatibility complex (MHC) class I antigens which expressed on extra villous cytotrophoblast, which interacts with NKG2A, is an inhibitory receptor on natural killer (NK) cells and leading to down regulation of immune response in the maternal-fetal interface and provides maternal immune tolerance of the fetus. Objective: This study was designated to investigate the gene frequencies of E0101 and E0103 in HLA-E gene in Iranian women with recurrent spontaneous abortion (RSA). Materials and Methods: Amplification Refractory Mutation System (ARMS-PCR) technique was carried out to detect polymorphism in exon 3 of the HLA-E gene in women with RSA and controls (n=200). Differences between groups were analyzed by SPSS19 software using 2 test. Results: There was no significant difference in the allele frequencies of the HLA-E polymorphism between RSA and fertile controls but HLA-E 0101/0103 heterozygous genotype was found to be significantly higher in RSA group (p=0.006, OR=1.73), so this genotype might confer susceptibility to RSA. Conclusion: Our results suggest that HLA-E 0101/0103 heterozygous genotype leads to increase of RSA risk. It seems that by genotyping of HLA-E polymorphism, we can predict the risk of RSA in infertile women.