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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 (P =.03 and P =.03, respectively). Autoimmune-negative patients had lower expression of LRBA and CTLA-4 than the control group, although it was not significant. There was a positive correlation between the expressions of LRBA and CTLA-4 in both groups of patients (P <.05). Furthermore, the highest frequency of LRBA (85.7%) and CTLA-4 (71.4%) defects was detected in those with concomitant presence of autoimmunity, enteropathy, and early-onset occurrence. Concurrent presence of autoimmunity, enteropathy, and early-onset occurrence in CVID patients could be indicative of a lack of expression in LRBA and CTLA-4 proteins. This could be helpful in early diagnosis and initiation of appropriate treatment in these patients prior to genetic confirmation. [ABSTRACT FROM AUTHOR]

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 < 0.05). None of the dietary patterns were associated with circulating IL‐17 levels. Conclusions: Higher consumption of fruits and vegetables is inversely associated with serum hs‐CRP but not IL‐17 levels. Studies investigating the dietary patterns in association with IL‐17 in other populations are recommended. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 theIL-23Rgene 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 (pvalue = 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. [ABSTRACT FROM PUBLISHER]

Background and Objective: Methamphetamine has strong stimulating effects on various systems of the human body. The aim of this study was to evaluate the hematological and biochemical parameters in methamphetamine addicts and to compare them with healthyindividuals. Methods: This is a retrospective case-control study that was conducted in 1390-91 in Ibn Sina Hospital in Shiraz, Iran. Measurement of lipids (cholesterol, triglycerides), liver enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase), albumin, blood urea nitrogen, creatinine and blood parameters such as platelets and white blood cells(WBCs) count, hemoglobin concentration and hematocrit of 60 individuals addicted to methamphetamine and 60 healthy subjects as a control group was carried out. Results: Alanine aminotransferase, aspartate amino transferase, alkaline phosphatase, WBCs and platelet count and serum creatinine levels in methamphetamine addicts were significantly higher than the control group(p-value <0.001), while hemoglobin, hematocrit and albumin levels were lower in these patients (p-value <0.001). Conclusion: The use of methamphetamine increases lipid peroxidation, changes levels of inflammatory markers and increases liver enzymes, which may increase the risk of liver diseases. It also increases WBCs and platelets count as an early sign of inflammatory disease progression, associated with methamphetamine abuse. Decreased hemoglobin and hematocrit can also increase the risk of anemia in these patients. These observations may give us a better understanding about the biological mechanisms associated with the pathology of methamphetamine consumption in Iran and help us prevent and solve the problems arising from this drug. [ABSTRACT FROM AUTHOR]

The SNP (rs11209026, Arg381Gln, R381Q) in the IL-23 receptor (IL23R) confers protection against multiple inflammatory diseases, representing one of the most significant human genetic polymorphisms in inflammatory diseases. We, therefore, investigated the association between IL-23 R R381Q gene polymorphism and asthma. This case-control study was performed on 209 patients, and 200 healthy controls. Using PCR-RFLP, the R381Q variant was screened in the IL-23R gene of the patients and controls. Serum IgE levels were measured using ELISA technique. Eosinophil absolute count was done with Sesmex cell counter. Our results indicated that the genotype and allele frequencies of the IL-23R R381Q polymorphism is significantly different between asthmatic patients and control subjects (p<0.001; odd ratio= 0.266; 95%, CI=0.118-0.604. Moreover, the asthmatic patients had higher eosinophil count and total serum IgE levels than controls as expected (p<0.001). The present study suggested that R381Q polymorphism in IL-23 receptor may be a predisposing allele for asthma. [ABSTRACT FROM AUTHOR]

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 X2 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. [ABSTRACT FROM AUTHOR]

Background: Asthma is one of the respiratory disorders caused by chronic airway inflammation. IL-4 has been identified as one of the participating interleukins in the severity of asthma., Objective: A case-control study was conducted to determine the association of rs1805010, a single nucleotide polymorphism in the interleukin 4 receptor α chain, with asthma and immunoglobulin E and IL-17A serum levels in Iranian populations., Methods: ELISA was used to investigate the relationship between three different varieties of SNP I50V and serum IL-17A levels, as well as total IgE levels. Based on GINA criteria, patients were classified into mild, moderate, and severe groups based on the association between SNP I50V, IL-17A, and total IgE. In order to analyze the data, the student-t-test and the one-way ANOVA were used., Results: The SNP I50V was associated with asthma in a significant way (p = 0.001). IL-17A and total IgE levels were significantly higher in asthmatic patients than in control participants (p 0.05 and p 0.021, respectively), but neither showed any association with SNP I50V in the asthmatic patients., Conclusion: Asthma patients have a higher prevalence of the I allele, reflecting the significance of Th2 cells. Although total IgE and IL-17A levels increased in both disease subgroups, total IgE level augmentation correlates directly with disease severity, while IL-17A level enhancement does not., Competing Interests: The authors declare no conflict of interest, financial or otherwise., (© 2024 Mowahedi et al.)