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Acute T-cell-mediated rejection of the renal allograft is a serious posttransplant challenge that requires administration of high-dose immunosuppressive drugs with considerable side effects; therefore, specific targeting of T-cell responses may improve both prevention and treatment of T-cell-mediated rejection. A potential candidate for this purpose is interferon regulatory factor 4 because of its implication in differentiation and function of T cells. Our aim was to evaluate the frequency of the rs872071AG and rs12203592CT single-nucleotide polymorphisms of the interferon regulatory factor 4 gene and association of these 2 polymorphisms with the gene expression of programmed cell death 1 and Helios in patients with T-cell-mediated rejection versus stable recipients.Sixty recipients with T-cell- mediated rejection and 60 age-matched and sex-matched stable recipients were recruited. Two single-nucleotide polymorphisms of interferon regulatory factor 4 gene, as well as the expression of programmed cell death 1 and Helios genes in peripheral blood mononuclear cells, were investigated with real-time polymerase chain reaction.Programmed cell death 1 gene expression was reduced in patients with T-cell-mediated rejection versus stable recipients (P = .03). The frequency of rs872071AG and rs12203592CT single-nucleotide polymorphisms showed no significant difference between groups. Presence of the rs12203592CT single-nucleotide polymorphism was directly correlated with the expression of programmed cell death 1 gene (P = .049), and rs872071AG positivity was directly correlated with Helios gene expression (P = .008), which suggests an inhibitory role for interferon regulatory factor 4 on programmed cell death 1 and Helios molecules.Programmed cell death 1 gene expression was lower in patients with T-cell-mediated rejection versus stable recipients. Low-expressing singlenucleotide polymorphisms of interferon regulatory factor 4 could enhance the downstream gene expression of programmed cell death 1 and Helios immunoregulatory molecules. Therefore, specific inhibition of interferon regulatory factor 4 may promote tolerance induction in the allograft.

The major current focus on treating rheumatoid arthritis is to put an end to long-term treatments and instead, specifically block widespread immunosuppression by developing antigen-specific tolerance, while also permitting an intact immune response toward other antigens to occur. There have been promising preclinical findings regarding adoptive Treg cells immunotherapy with a critically responsible function in the prevention of autoimmunity, tissue repair and regeneration, which make them an attractive candidate to develop effective therapeutic approaches to achieve this interesting concept in many human immune-mediated diseases, such as rheumatoid arthritis. Ex vivo or invivo manipulation protocols are not only utilized to correct Treg cells defect, but also to benefit from their specific immunosuppressive properties by identifying specific antigens that are expressed in the inflamedjoint. The methods able to address these deficiencies can be considered as a target for immunity interventions to restore appropriate immune function.

Background: nutritional factors might affect the number and function of immune cells for instance the production of cytokines and immunoglobulins. Ramadan fasting is intermittent abstinence from eating and drinking for almost four weeks. Aim: The present study aimed to investigate the influence of intermittent fasting on serum IgA, salivary IgA (sIgA), interleukin (IL)-17, and IL-22 levels. Methods: 40 healthy men aged 19–29 years were evaluated before and during the fourth week of Ramadan fasting for IgA levels by the nephelometric method as well as salivary IgA (sIgA), IL-17, and IL-22 amounts using enzyme-linked immunosorbent assay (ELISA). Results: serum IgA levels reduced significantly at the end of Ramadan fasting (225.8 ± 87 vs. 196 ± 70 mg/dl) (p-value

Spondyloarthropathies (SpA) refer to a multifactorial disease affecting the axial and peripheral skeleton, mainly in the larger joints of the lower limbs. The exact mechanism that causes most SpAs is still vague; however, it is clear that both genetics and environmental factors are involved in the pathogenesis of the disease. Environmental factors directly implicate innate immunity, which is a vital compartment in triggering autoinflammatory disorders. To date, only a few studies specifically focused on the potential role of these factors, including mechanical, psychological, and oxidative stresses, smoking, diet, and infections. Here we discuss the contribution of named stresses and related molecular mechanisms on SpA diseases, apart from the diet and infection, which were the concept of previous chapters.

Spondyloarthropathies (SpA) that include ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, arthritis associated with inflammatory bowel disease, including Crohn’s disease and ulcerative colitis, are genetic and immune-mediated disorders that manifest various clinical symptoms, mainly spine stiffness and chronic back pain and simultaneous inflammation in extra-axial biomechanically stressed sites. Innate and adaptive immune responses are complementary features of body defense. Previously, many have been written about the role of adaptive immunity in axSpA, which is reasonable given the HLA-B27 association and several other genetic indicators concerning adaptive immunity. Recent classification has specified spondyloarthropathies as the transitional between autoimmunity and autoinflammatory disease which the latter term implies a remarkable role in innate immune dysregulation. The purpose of this study is to clarify the innate immunity contribution in disease initiation and outcomes of SpA disorders.

Spondyloarthropathies (SpAs) are a debilitating group of chronic autoimmune diseases that affect a considerable proportion of young adults causing medical, social, and economical consequences. The prominent feature of SpAs is positive familial history and presence of HLA-B27 in most patients, which suggests genetic predisposing factors in disease pathogenesis. Ankylosing Spondylitis (AS), being the most prevalent and severe form of SpAs, is generally characterized by inflammatory low back pain accompanied by radiological findings of sacroiliitis. Despite all radiological and laboratory advancements, the complicated manifestations of AS urges for multi-factorial diagnostic criteria evolved during recent years for efficient detection and follow-up of the patients. According to the inflammatory base of SpAs, various anti-inflammatory medications have been used for treating the patients ranging from nonsteroidal anti-inflammatory drugs to Disease-modifying anti-rheumatic drugs, including synthetic and biologic agents. In the present chapter, we provide a general overview of epidemiologic, diagnostic, pathophysiologic, and therapeutic aspects of Spondyloarthropathies.

Immune monitoring of transplanted patients may provide a reliable basis for the individualization of immunosuppressive therapy. In addition, it might be applied for realizing the early and non-invasive diagnosis of acute allograft rejection.Percentages of TCD4 + IL-17+ (Th17) and TCD4 + CD25 + CD127Six months post-transplant, the percentage of Th17 and Treg cells in the peripheral blood of stable liver transplant recipients reduced significantly, but the Th17/Treg ratios were comparable to the pre-transplant period (1.24 vs. 1.56); however, Th17/Treg ratios in the rejection group was significantly higher than in the stable recipients (4.06 vs. 1.56, P-value = 0.001). Stable patients showed decreased amounts of serum IL-17 which was remarkably lower than in the rejection group (P-value = 0.01). Moreover, there was a significant correlation between the serum level of IL-17 and the percentage of Th17 cells (P-value0.001). Th17 frequency was negatively associated with the liver allograft function. Notably, TGF-β1 levels differed neither between pre-and post-transplant samplings nor between stable and rejection groups.Six months after liver transplantation, the mean Th17/Treg ratio in stable recipients remained comparable to the pre-transplant values; however, it was significantly elevated in patients with acute allograft rejection, suggesting the Th17/Treg ratio as a probable predictor of acute rejection.

Particulate matter (PM) as the carcinogenic air pollutants can lead to aggravated health outcomes. Epidemiological studies demonstrated that PM can be engaged in different diseases such as cardiovascular, respiratory and cancer. The in vitro secretion of proinflammatory cytokines by human peripheral blood mononuclear cells (PBMCs) has been used to assess the effects of PM with an aerodynamic diameter

Laboratory and epidemiological researches have indicated that ambient air particulate matter have a plays critical role in causing diseases. The current research evaluated the chemical attributes of PM2.5 in the ambient air of the cities of Karaj and Fardis and determined its toxicological effects on human lung epithelial cells (A549). In the study city, 16 points were selected from the two high-traffic and low-traffic points for sampling. A sampling of ambient air was carried out in spring, summer, autumn, and winter 2018–19. Air sampling was performed for 24 h according to the EPA-TO/13A guidelines. To analyze of toxic metals and polycyclic aromatic hydrocarbons (PAHs), ICP-OES and GC-MS were used, respectively, and for cell toxicity analysis, an ELISA reader was used. Then from SPSS, Excel and R software were used for statistical analysis. The results of the current study indicated that the concentration of PAHs carcinogenic in the autumn season in high-traffic stations was the highest and equal to 9.3 ng/m(3), and in the spring season in the low-traffic stations, it was the lowest and equal to 5.82 ng/m(3). In general, during the period of study, Heavy metals including Zn, Fe, Pb, Cu, and Al had the highest concentration compared to other metals. However, Hg, Cr, As, Pb, Cu, Cd, and Zn were higher concentration in the winter and autumn seasons than in the spring and summer seasons. Cell viability measurements by using MTT showed that low-traffic and high-traffic stations had the highest toxicity in autumn season compared to other seasons. (p

Renal transplant rejection is one of the clinical challenges, which usually requires administration of immunosuppressive drugs causing serious side effects. Therefore, invention of effective and specific therapeutics is necessary to control undesired immune responses particularly T-cell reactions to allograft. Interferon Regulatory Factor-4 (IRF-4) due to its implication on T cells differentiation and function might be targeted to treat T cell-mediated cellular rejection (TCMR). The aim of this study was to investigate the association between IRF-4 gene expression and acute TCMR, as well as to examine the correlation between IRF-4 gene expression and cellular expression of Programmed cell death-1 (PD-1) and Helios molecules.Peripheral blood samples were obtained from 30 patients with biopsy proven acute TCMR and 30 stable recipients. IRF-4 gene expression was quantified using RT-PCR, and cellular expression of PD-1 and Helios were evaluated with flowcytometry.IRF-4 gene expression was significantly increased in acute TCMR patients compared with stable recipients (P.05). Helios protein expression was slightly decreased in TCMR group but this was not statistically significant. There was a negative correlation between IRF-4 gene expression and PD-1 as well as Helios frequency in the whole studied population.IRF-4 expression increases in acute TCMR which might also lead to a diminished expression of downstream immunoregulatory molecules such as PD-1 and Helios. Therefore, specific inhibition of IRF-4 may be helpful in managing acute TCMR.

OBJECTIVES Protein tyrosine phosphatase non-receptor type 22 gene (PTPN22) single-nucleotide polymorphisms (SNP) have been associated with a number of different autoimmune diseases. This study aimed to investigate the association of five polymorphisms of PTPN22 gene with susceptibility to ulcerative colitis (UC) in Iran. MATERIALS AND METHODS A total of 67 patients diagnosed with UC (35 female and 32 male all under 18 years) and 93 healthy subjects were selected. The samples were genotyped for the, rs12760457, rs2476601, rs1310182, rs1217414, and rs33996649 in PTPN22 gene using real-time polymerase chain reaction (PCR) allelic discrimination TaqMan genotyping assays. RESULTS The frequencies of the rs1310182 A and G alleles, and also the AA and GG genotypes were significantly different between the patient and the control groups (p

The particulate matter has become a serious health problem in some large cities in the world. These particles are a complex mixture of chemical compounds which change based on location and time and, consequently, can cause different health-related effects. The exact mechanism of the effect of these particles is not yet known for certain. However, it seems that numerous mechanisms through the production of ROS and, eventually, DNA destruction, which are related to a wide range of diseases, are among the causes of particles’ health-related effects. The present study is aimed to evaluate and compare the genotoxicity potential of particles collected in Tehran, Iran, in urban and rural regions during spring and autumn as well as dusty and inversion conditions. These effects were examined using the comet assay on human pulmonary epithelial cells (A549). Results showed that all the particles had the potential for genotoxicity at the concentration used in this study (75,150 and 300 μg/ml). Moreover, DNA destruction changed with season, site, and even dusty and inversion atmospheric conditions. These changes mostly belonged to urban particles. In general, urban particles in autumn and, specifically, on days with inversion had higher genotoxicity (p

Ankylosing spondylitis (AS) is an inflammatory autoimmune disease. AS is a prototype form of spondyloarthropathies (SpA). The precise etiology of AS has not been fully understood. But Inflammation has a critical role in the pathogenesis of the disease. The immune system by various cells, secreted-mediators and markers manage and regulate the immune responses and inflammation. Every factor which disturbed this regulation and hemostasis can cause chronic inflammation. In this review, we discussed the role of several innate and adaptive immune cells involved in the triggering, initiation, development, and regulation of AS.

Graphical abstract, The International Agency for Research on Cancer (IARC) has defined outdoor air pollution and PM as the human carcinogen (Group 1), which mainly cause an increased risk of lung cancer. Scientists have considered epigenetic modifications as a possible mechanism to deal with adverse effects of air pollution. This study aimed to compare the effect of airborne PM10 (PM with aerodynamic diameter ≤10 μm) on in vitro global methylation in human peripheral blood mononuclear cells (PBMCs). PM10 was sampled in metropolitan Tehran, the capital of Iran. PBMCs were extracted from whole blood of healthy males and treated with PM10 suspension at concentrations of 50–300 μg/mL for 4 h. Untreated cells were used as the negative control. Genomic DNA was extracted from each sample using the DNA blood mini kit according to the manufacturer’s instruction. Moreover, 5-methylsytosine (%5-mC) and 5-hydroxymethylcytosine (%5-hmC) were measured by the enzyme-linked immunosorbent assay (ELISA) method. %5-mC and %5-hmC in each sample was compared with negative control and reported as difference %5-mC and %5-hmC.

Sirtuin 1, a member of sirtuin family of histone deacetylase enzymes, has been implicated in a variety of physiologic and pathologic events, including energy metabolism, cell survival, and age-related alterations. In view of the anti-inflammatory properties of sirtuin 1 along with its protective role in ischemia reperfusion injury, it might be considered as contributing to the promotion of transplantation outcome. However, the potential ability of sirtuin 1 to induce malignancies raises some concerns about its overexpression in clinic. Moreover, despite the findings of sirtuin 1 implication in thymic tolerance induction and T regulatory (Treg) cells survival, there is also evidence for its involvement in Treg suppression and in T helper 17 cells differentiation. The identification of sirtuin 1 natural and synthetic activators leads to the proposal of sirtuin 1 as an eligible target for clinical interventions in transplantation. All positive and negative consequences of sirtuin 1 overactivation/overexpression in the allograft should therefore be studied thoroughly. Herein, we summarize previous findings concerning direct and indirect influences of sirtuin 1 manipulation on transplantation.

BackgroundPrimary membranous nephropathy (PMN) is an autoimmune disease affecting renal glomerulus, characterized by autoantibodies aggregation on podocytes and subsequent epithelial thickening. Therefore, rituximab, an anti-CD20 monoclonal antibody, is used to treat patients with the deteriorating condition.ObjectivesAssuming that rituximab demolishes a considerable number of B-lymphocytes and causes transient immunodeficiency, we aimed to identify B cell subsets involved in PMN pathogenesis to facilitate specific targeting.MethodsUsing flowcytometery, 25 PMN patients including 15 on standard treatment and 10 on standard treatment plus rituximab were enrolled to compare with healthy controls. Rituximab-receiving patients were studied before and two months after administration.ResultsNeither total CD19+ nor memory B cell percentages showed significant differences between the study groups. However, the number of B regulatory cells (Breg) was lower in both standard-treatment and Rituximab-receiving patients than in controls. Moreover, the percentage of naive/mature B cells dropped after standard treatment.ConclusionsPMN patients seem to possess an insufficient percentage of Breg cells, which are involved in immunomodulation. Furthermore, the standard-treatment group showed a reduced count of naive/mature B cells, which constitute a substantial proportion of normal B lymphocytes population.

PURPOSE: This study aimed to investigate chemical composition of PM(10) (particulate matter with aerodynamic diameter ≤ 10 μm) during dust storm and inversion in Tehran and hemolysis effects. METHODS: PM(10) was sampled in Tehran, Iran, during dust storm and inversion conditions. Water soluble ions (F¯, Cl¯, NO(2)¯, NO(3)¯, SO(4)¯(2), Na(+), K(+), NH(4)(+), Ca(+2), Mg(+2)) and elements (Al, Ba, Cd, Co, Cr, Cu, Fe, Li, Mn, Mo, Ni, Pb, Se, Sn, Sr, V, Zn, Pt, Rh, Pd, As and Si) were analyzed by ion chromatograph (IC) and inductively coupled plasma optical emission spectrometer (ICP-OES), respectively. Hemolysis was examined as in vitro at PM(10) concentrations of 50–300 μg/ml. RESULTS: Daily average of PM(10) concentrations in dusty and inversion days were 348.40 and 220.54 μg/m(3), respectively. Most prevalence ionic components were NO(3)¯, Cl¯, SO(4)¯(2) and Ca(+2) during dust storm and SO(4)¯(2), NO(3)¯, Cl¯ and NH(4)(+) during inversion. Si, Fe and Al had the maximum values in both conditions. Particles associated with both conditions induced hemolytic responses. PM(10) from dusty day showed a higher hemolysis percent (10.24 ± 4.67%) than inversion (9.08 ± 5.47%), but this difference was not significant (p = 0.32). Hemolytic effects were significantly intensified by increased PM concentrations (p

Particulate matter (PM) as the carcinogenic air pollutants can lead to aggravated health outcomes. Epidemiological studies demonstrated that PM can be engaged in different diseases such as cardiovascular, respiratory and cancer. The in vitro secretion of proinflammatory cytokines by human peripheral blood mononuclear cells (PBMCs) has been used to assess the effects of PM with an aerodynamic diameter

Significant advances have been achieved in recent years to ameliorate rheumatoid arthritis (RA) in animal models using gene therapy approaches rather than biological treatments. Although biological agents serve as antirheumatic drugs with suppressing proinflammatory cytokine activities, they are usually accompanied by systemic immune suppression resulting from continuous or high systemic dose injections of biological agents. Therefore, gene transfer approaches have opened an interesting perspective to deliver one or multiple genes in a target-specific or inducible manner for the sustained intra-articular expression of therapeutic products. Accordingly, many studies have focused on gene transferring methods in animal models by using one of the available approaches. In this study, the important strategies used to select effective genes for RA gene therapy have been outlined. Given the work done in this field, the future looks bright for gene therapy as a new method in the clinical treatment of autoimmune diseases such as RA, and by ongoing efforts in this field, we hope to achieve feasible, safe, and effective treatment methods.

The original version of this article unfortunately contained a mistake. Figure 6 caption should be "The light microscopic image (a) and transmission electron microscopic image (b) of A549 cell after 24 h of exposure to PM10 (150 μg/ml).

Please note that the corresponding author’s correct affiliation is “Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Objective: Angiotensin converting enzyme (ACE) converts angiotensin I into angiotensin II. The ACE gene shows an I/D polymorphism, which correlates with ACE concentrations. The aim of this study is to evaluate the distribution of the ACE I/D genotype in children with idiopathic nephrotic syndrome (INS) and healthy controls and study the effect of this polymorphism on clinical and pathologic findings. Methods: ACE gene I/D polymorphism of 104 patients with INS and 119 controls were determined. Results: The DD, ID, and II genotypes were found in 58.7%, 22.1%, and 19.2% of the patients, and in 79.8%, 2.5%, and 17.6% of controls, respectively (p > 0.05). The ID genotype was seen more frequently in patients resistant to treatment. Conclusion: The observed differences with previous reports suggest the influence of the genetic background on disease course. The ACE I/D gene polymorphism's role seems to be more important in renal disease progression than susceptibility.

Purpose: This study was performed in 24 members of a family with spontaneous pneumothorax to test clinical suspicion of Birt–Hogg– Dube syndrome (BHDS). Methods: Computed tomography scan was performed for confirmation of pneumothorax, while genetic tests were done using real-time quantitative polymerase chain reaction. Results: Genetic studies showed a deletion of exon 1 in the FLCN gene in the index case as well as nine other individuals, including two with clinical phenotypes of pneumothorax and seven who are symptom-free to date. Conclusions: Proper imaging and taking accurate family history could be the keys to test clinical suspicion in some syndromes, including BHDS.

Programmed cell death 1 (PDCD-1, also named PD-1, CD279, and SLEB2), a negative T cell regulator to maintain peripheral tolerance, induces negative signals to T cells during interaction with its ligands and is therefore a candidate gene in the development of autoimmune diseases such as rheumatoid arthritis (RA). Herein, we investigate the association of PDCD-1 polymorphisms with the risk of RA among Iranian patients and healthy controls.Genomic DNA was extracted from the whole blood samples using DNA Purification kit (DNG-plus). Using the PCR- RFLP method, 3 PDCD-1 SNPs, including PD1.1G/A, PD1.3G/A, and PD1.9C/T were genotyped in 120 RA patients as well as 188 healthy controls. The genotype and allele frequencies of these SNPs were analysed by statistical tests for the significant association between RA patients and controls. Haplotype constructions of these SNPs were performed. Clinical diagnosis of the RA patients was confirmed by the Rheumatology Research Centere of Tehran University of Medical Sciences.Our study revealed that PD1.1 A allele at position -538 in the promoter region of PDCD-1 gene is associated with an increased risk of RA disease compared to controls (2.9% vs. 0.7%, OR= 3.735, 95% CI= 0.956-14.588, p=0.046). There were no significant differences in other alleles and genotypes of PDCD-1 SNPs between RA cases and controls.Our results indicate that among the polymorphisms which we evaluated only the PD1.1A allele in the promoter region of PDCD-1 gene is significantly associated with RA susceptibility in Iranian patients.

Ankylosing spondylitis (AS) is a chronic inflammatory disease, characterized by axial arthritis in which the genetic-environmental factors seem to be involved in the pathogenesis of the disease. This study was performed to investigate the role of polymorphisms of the programmed cell death 1 (PDCD1) gene on susceptibility to AS. In this study, 161 Iranian patients with AS and 208 normal controls were enrolled; two single-nucleotide polymorphisms (SNPs) of the PDCD1 gene PD-1.3 (G, A) in nucleotide position +7146 of intron 4 and PD-1.9 (C, T) in nucleotide +7625 of exon 5 were studied. Analysis of PD-1.3 revealed that 82% of patients and 79% of controls had GG genotype, while GA and AA genotypes were detected in 17% and 0.6% of patients, respectively, and 20% and 1.4% of controls, respectively. Moreover, the genotype CC (PD-1.9) was present in 92% of patients and 97% of controls. Although these differences were not statistically significant between patients and controls, comparisons of genotypes frequencies in the AS patients, based on human leukocyte antigen (HLA)-B27, revealed that all patients who had CT genotype (PD-1.9) were HLA-B27 positive, whereas 30% of patients with CC genotype were HLA-B27 negative. There was no evidence of association for PDCD1 SNPs with AS in our study, but CT genotype (PD-1.9) seems to be associated with HLA-B27 positivity in the patients with AS.

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a costimulatory molecule expressed by activated T cells. This study was performed to investigate the allele and genotype frequencies of CTLA4 gene polymorphisms in Iranian patients with ankylosing spondylitis (AS).One hundred and fifty-seven patients with AS and 103 controls were included in this study. Polymorphisms of CTLA4 gene at positions +49 (in exon 1), -318, and -1,147 (in the promoter region) were studied on the genomic DNA using PCR restriction fragment-length polymorphism method.The frequencies of the T allele at position -1147 in the patients with AS was significantly increased in comparison with the control group (11% vs. 5%, P = 0.004); whereas the frequencies of C allele at the same position were significantly decreased in the patient group (89% vs. 95%, P = 0.004). Comparison of genotype frequencies at this position showed that the frequency of CT genotype in comparison with other genotypes was overrepresented in the patient group (20% vs. 8%, P = 0.012), while the CC genotype in comparison with other genotypes was decreased (79% vs. 91%, P = 0.012). There was no significant difference on frequencies of genotypes at the positions -318 and +49.This study could suggest an association between specific allele in the promoter region of CTLA4 gene and AS disease.