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Background: Few studies have evaluated COVID-19 vaccine efficacy in patients with inborn errors of immunity (IEI).Objective: To evaluate the levels of antibody (Ab) production and function after COVID-19 vaccination in IEI patients with phagocytic, complement, and Ab deficiencies and their comparison with healthy controls.Methods: Serum samples were collected from 41 patients and 32 healthy controls at least one month after the second dose of vaccination, while clinical evaluations continued until the end of the third dose. Levels of specific anti-receptor-binding domain (RBD) IgG and anti-RBD neutralizing antibodies were measured using EUROIMMUN and ChemoBind kits, respectively. Conventional SARS-CoV-2 neutralization test (cVNT) was also performed. Cutoff values of ≤20, 20-80, and ≥80 (for cVNT and Chemobined) and 0.8-4.2, 4.2-8.5, and ≥8.5 (for EUROIMMUN) were defined as negative/weak, positive/moderate, and positive/significant, respectively.Results: A considerable distinction was observed between the Ab-deficient patients and the controls for Ab concentration (EUROIMMUN, p

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder more common in autosomal recessive (AR) than X-linked in Iran. This study aimed to assess whether having a child with AR-CGD would increase the likelihood of the next child being affected by CGD. Ninety-one families with at least one child affected by AR-CGD entered this study. Out of the 270 children, 128 were affected by AR-CGD. We used a cross tab for the odds ratio (OR) calculation, in which exposure to a previously affected child and the next child’s status were evaluated. This study illustrated that the chances of having another child afflicted with AR-CGD are significantly increased if the previous child had AR-CGD (OR=2.77, 95% CI=1.35-5.69).Althoug h AR disorders affect 25% of each pregnancy, we showed that the chance that the next child would be affected by CGD, given that the previous child was affected, is 2.77 times greater than in families with a normal child. It is recommended to warn families with one or more affected children to evaluate the risk of CGD in their subsequent pregnancies with prenatal diagnosis.

Abstract Background Preliminary studies revealed the safety and effectiveness of convalescent plasma (CP) therapy for patients with coronavirus. In this study, we aimed to evaluate and summarize the available evidence on CP therapy, identify the research gap regarding the immunological response to CP therapy and pave the road for future studies. Methods This study was conducted according to the Hilary Arksey and Lisa O’Malley framework. To find out the relevant studies, we searched PubMed, Scopus and Embase databases up to 30th May 2021. Data have been extracted according to three categories: (1) patients’ characteristics, (2) clinical and immunological responses to CP therapy and (3) pre-infusion screening of the CP samples. Results A total of 12,553 articles were identified. One hundred fifty-four studies met the inclusion criteria for full-text review. More than half of the included studies (112 studies, (75.6%)) concluded satisfactory outcomes and or safety of CP infusion in patients. Results of studies showed the efficacy of CP therapy in clinical improvement (101 studies), decreasing in the level of inflammatory factors (62 studies), elimination or decreasing in viral load (60 studies), and induction or increase in antibody response (37 studies). Despite these promising results, the results of the 49 studies revealed that CP therapy was ineffective in the survival of patients, clinical improvement, viral infection elimination or decrease in the inflammatory factor levels. Furthermore, the adaptive immune response was evaluated in 3 studies. Information related to the pre-infusion screening for human leukocyte antigen/human neutrophil antigen (HLA/HNA) antibodies was not reported in most of the studies. Our gap analysis revealed that the influence of the CP infusion on the adaptive immune and inflammatory responses in patients with coronavirus needs further investigation. Conclusions Based on the results of most included studies, CP infusion was safe and resulted in clinical improvement of patients and decreasing the viral load. The effect of the CP infusion on adaptive immune response and inflammatory cytokines in patients with coronavirus needs further investigation.

Abstract Inflammatory biomarkers in exhaled breath condensate (EBC) are measured to estimate the effects of air pollution on humans. The present study was conducted to investigate the relationship between particulate matter and inflammatory biomarkers in blood plasma and exhaled air in young adults. The obtained results were compared in two periods; i.e., winter and summer. GRIMM Dust Monitors were used to measure PM10, PM2.5, and PM1 in indoor and outdoor air. A total of 40 healthy young adults exhaling air condensate were collected. Then, biomarkers of interleukin-6 (IL-6), Nitrosothiols (RS-NOs), and Tumor necrosis factor-soluble receptor-II (sTNFRII) were measured by 96 wells method ELISA and commercial kits (HS600B R&D Kit and ALX-850–037-KI01) in EBC while interleukin-6 (IL-6), sTNFRII and White Blood Cell (WBC) were measured in blood plasma in two periods of February 2013 (winter) and May 2013 (summer). Significant association was found between particulate matter and the white blood cell count (p

Early diagnosis of primary immunodeficiencies is crucial for timely treatment and preventing unwanted complications. Next-generation sequencing (NGS) and detailed clinical and immunological evaluation can help early detect such disorders. This study aimed to confirm the diagnosis of two cases of autosomal recessive hyper-immunoglobulin E (IgE) syndrome (AR-HIES), presenting with irreversible eye involvement. Two unrelated patients with suspected AR-HIES were referred to the Immunology, Asthma and Allergy Research Institute (IAARI), Tehran, Iran. Immunological screening tests were performed for AR-HIES, which showed elevated serum IgE levels, eosinophilia, and low T-lymphocyte responses. NGS was performed, and the results were confirmed by Sanger sequencing. Sequence analysis showed a mutation in intron 17 of the dedicator of cytokinesis 8 (DOCK8) gene in the first patient, and a homozygous three base-pair deletion in exon 45 of DOCK8 in the second patient. This is the first time such mutations are reported and these variants are predicted to be damaging. Both patients suffered from persistent viral infections along with cytomegalovirus (CMV) retinitis. Suspicion of these two novel DOCK8 mutations can benefit patients presenting with recalcitrant ophthalmic viral involvements and relevant immunological test results. This would lead to earlier referrals for immunologic and genetic confirmation and thus, a more timely intervention with hematopoietic stem cell transplantation (HSCT).

Objective. Human neutrophil antigens (HNAs) can be targeted by HNA-allo antibodies and cause a variety of clinical conditions such as transfusion-related acute lung injury (TRALI) and neonatal alloimmune neutropenia (NAIN). The current study is aimed at identifying the genotype and allele frequencies of HNAs in Iranian blood donors. Methods. A total of 150 blood samples were obtained from healthy blood donors. HNA-1, HNA-3, HNA-4, and HNA-5 were genotyped, using the polymerase chain reaction sequence-specific primer (PCR-SSP) technique. The expression of the HNA-2 antigen on the neutrophil surface was evaluated by flow cytometry. Results. The allele frequencies of FCGR3B∗1 (encoding HNA-1a), FCGR3B∗2 (encoding HNA-1b), and FCGR3B∗3 (encoding HNA-1c) were 0.34, 0.63, and 0.03, respectively. For HNA-3, the allele frequencies for SLC44A2∗1 (encoding HNA-3a) and SLC44A2∗2 (encoding HNA-3b) were 0.63 and 0.37, respectively. The frequencies of ITGAM∗1 (encoding HNA-4a) and ITGAM∗2 (encoding HNA-4b) alleles were 0.85 and 0.15, respectively. Furthermore, the frequencies of ITGAL∗1 (encoding HNA-5a) and ITGAL∗2 (encoding HNA-5b) alleles were 0.72 and 0.28, respectively. In the studied population, HNA-2 antigen was present on the neutrophil surface in 97.3% of the individuals, while no detectable HNA-2 expression was observed in 2.7% of the individuals. However, no significant difference in HNA-2 expression between different age groups was found. Conclusion. The present study provides the first report of the HNA allele and genotype frequencies among the Iranian population. All HNAs (HNA-1 to HNA-5) were typed using the PCR-SSP and flow cytometer. In the current cohort study, the determined HNA allele frequencies were similar to the previous reports from British, German, and Danish populations. Considering the presence of different Iranian ethnic groups, further studies with a larger sample size are needed to draw a total picture for HNA allele frequencies.

Autoimmune neutropenia is a type of immune-mediated neutropenia, caused by antibody-induced neutrophil destruction. Here we report two cases (3-year-old boy and 9-year-old girl) with suspected autoimmune neutropenia. The presence of neutrophil antibodies in sera of these patients was investigated using standard neutrophil antibody screening tests such as granulocyte immunofluorescence test (GIFT), granulocyte agglutination test (GAT), and lymphocyte immunofluorescence test (LIFT). A positive reactivity with two panel cells was found in GIFT. No reactivities with panel cells were observed in GAT and LIFT. To the best of our knowledge, this is the first report for detecting the neutrophil reactive antibodies using genotyped neutrophils in patients with autoimmune neutropenia in Iran. The final diagnosis of our patients was primary autoimmune neutropenia for the boy and autoimmune neutropenia associated with familial Mediterranean fever for the girl.

Meatal stenosis (MS) is known as one of the most frequent complications of circumcision. In the present study, we aimed to find any possible relationship between MS and allergic disorders. A total of 36 children with a mean±SD age of 5.84±2.03 years were referred with MS and an atopic background even in themselves or in one of their family members (Group A). There were also age-matched controls with a mean±SD age of 5.70±2.17 years who were referred to our center with allergic symptoms and no urinary complaints (Group B, n=17). The RIDA qLine allergy and allergy explorer (ALEX) tests were performed for all patients to find possible allergen sensitization. Laboratory findings revealed that IgE-sensitization to the main food and aeroallergens in Group A (with the chief complaint of MS in whom a mild atopic condition was found during concise medical history taking) were very similar to the control group with no significant difference (except for ryegrass which was higher in the control group). Although total IgE level was considerably higher in group B compared to group A, food sensitization to cow’s milk and ß-lactoglobulin was higher in asthmatic patients of group A compared to the controls. It seems that not all patients with MS should be considered as a complication of circumcision and undergo a surgical procedure for correction of the stenosis. Further investigations are required to determine the role of concise medical history taking and proper treatment of the allergic disorder to reduce failed surgical attempts in atopic boys with MS.

T-cell receptor excision circles (TREC)/Kappa-deleting recombination excision circles (KREC) assay has been recently recognized for detecting patients with primary (T- and/or B-cell) immunodeficiency (PID). We aimed to investigate the alterations of these biomarkers in some combined immunodeficiency patients compared to the healthy controls in different age groups. TREC and KREC were assessed in a total of 82 PID patients, most of them with exact genetic diagnosis (3 months to 42 years); using quantitative real-time-polymerase chain reaction (PCR). Patients had a final diagnosis of common variable immunodeficiency (n=23), ataxia-telangiectasia (AT) (n=17), hyper-IgE syndrome (HIES) (7 with DOCK8 deficiency, 4 with signal transducer and activator of transcription 3 (STAT3) deficiency, and 8 children with unknown genetic defects), Wiskott-Aldrich syndrome (WAS) (n=20), purine nucleoside phosphorylase (PNP)deficiency(n=1), dedicator of cytokinesis2 (DOCK2) deficiency (n=1), recombinase activating gene1 (RAG1) deficiency (n=1). Very low to zero amounts of TREC and/or KREC were detected in 14 out of 23 cases of common variable immunodeficiency (CVID), 14 out of 17 cases of AT, 8 out of 20 cases of WAS, 6 out of 7 cases of DOCK8-deficiency patients, 4 out of 8 cases of HIES with unknown genetic defects and all patients with defects in DOCK2, PNP, and RAG1. STAT3-deficient patients were normal for both biomarkers. All patients showed a significant difference in both markers compared to age-matched healthy controls. Our findings highlight that apart from severe types of T/B cell defects, this assay can also be used for early diagnosis the patients with late-onset of disease and even PIDs without a positive family history.

No effective antiviral drugs and vaccines are available for the treatment of patients with severe coronavirus 2019 (COVID-19). Therefore, available, safe, and inexpensive drugs and supplements such as melatonin are among the proposed options for controlling inflammation. We did a randomized, single-blind study in Imam Khomeini Hospital between June 30, 2020, and August 5, 2020. Mild to moderate COVID-19 patients aged 25-65 years were eligible to enter the study based on chest CT scan, clinical symptoms, and physician diagnosis. The intervention group was prescribed 6 mg of oral melatonin for 2 weeks, which consumed half an hour before bedtime every night in low light conditions. Clinical symptoms and C-reactive protein (CRP) were measured before and after treatment in the melatonin received and control (regular medications) groups. Among screened patients with COVID-19, 14 patients were assigned to receive melatonin, and 17 patients were considered as controls. A significant difference (p=0.005) between CRP 1 and CRP 2 levels (before and after using melatonin) was found in the melatonin group while this difference (p=0.069) was not significant in the control group. Also, the percentage of recovery (based on symptoms) in patients who took melatonin was higher than that of patients in the control group (85.7% VS 47.1%). The result of this study confirmed the effectiveness of melatonin in mild to moderate outpatients with COVID-19. More clinical trials on elderly, diabetic, obese patients and severe cases are suggested in future studies.

Air pollutants are capable to enter bloodstream through the nose, mouth, skin and the digestive tract. Hemolysis is the premature destruction of red blood cells (RBCs) membranes. This can affect metabolism of RBCs and reduce cell life. Each of these adverse effects could lead to anemia, jaundice and other pathological conditions. Hemolysis can induce by the mineral components adsorbed on the particles. The aim of this study was to evaluate hemolysis of RBCs treated by airborne PM10 (PM with aerodynamic diameter ≤ 10 μm) in vitro. Study had two main stages including sampling and preparation of PM10 suspension, and hemolysis test. Particle samples were collected by means of a high-volume sampler on fiberglass filters. The PM10 was extracted through dry ultrasonic method. Blood sample was incubated by PM10 at concentrations 50–300 μg/mL for 3 h. Hemolysis percent was assessed through measurement of Hemoglobin concentration in test samples and total blood hemoglobin (TBH) sample by the cyanmethemoglobin method. Analysis of variance (ANOVA) and Tukey post-hoc test were applied to compare mean values of hemolysis percent between different PM concentrations.Method used in current study is suggested for investigation of toxic effects of airborne particle matter (PM1, PM2.5 and PM10) on human RBCs. Method name: Effect of airborne particulate matter on hemolysis in vitro, Keywords: Cyanmethemoglobin, Hemoglobine, Hemolysis percent, Air pollution, Dry extraction, In vitro test, ASTM standard E2524-08, Hemolytic samples

This study aims to investigate the role of prenatal diagnosis (PND) in Iranian couples with a previous history of primary immunodeficiency disorders (PIDD) in their family. All referred couples with a family history of PIDD and a tendency for PND were included in this project. Based on gestational age, chorionic villus sampling (CVS) was performed to analyze the molecular defect of the fetus according to the previous gene defect of the affected case in the family. Postnatal confirmation was performed by immunological screening tests. In a total of 100 cases, CVS was not evaluated in 19 patients due to unwillingness (n=5), late prenatal referral (n=7), miscarriage before CVS (n=3), and female fetus with x-linked diseases in previous children (n=4). In the remaining 81 patients, heterozygous and homozygous mutations were found in 33 and 23 cases, respectively. The hemizygous mutation was obtained in 6 and no pathogenic mutations were found in 19 individuals. Postnatal evaluations revealed that a total of 65 babies were healthy, 32 fetuses were aborted (3 cases before CVS, 2 spontaneous abortions of a healthy and as affected fetus in the CVS subgroup, and 27 cases were aborted due to therapeutic causes). One fetus from the heterozygous subgroup was spontaneously aborted with severe combined immunodeficiency (SCID) and one fetus from the homozygous subgroup that was supposed to be healthy was affected by the autosomal dominant-chronic granulomatous disease (AR-CGD). The diagnostic error was 1.2%. PND is highly recommended in families with a history of PID in their previous child to prevent an affected baby being born and to reduce the government, family, and personal burden of these diseases.

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by genetic defects in the Bruton tyrosine kinase (Btk) gene. XLA is characterized as an antibody deficiency by recurrent bacterial infections, the absence of peripheral B cells, and profound reductions in all immunoglobulin isotypes. This study aims to report the clinical and genetic features of five Iranian patients with XLA. Five male cases with recurrent bacterial infection entered this study based on clinical evaluation and Immunological screening tests. The levels of T-cell receptor excision circle (TREC) and kappa-deleting recombination excision circle (KREC) were also measured in dried blood spot (DBS) samples. Sanger sequencing was applied to PCR products of DNA samples of the patients for genetic studies. All patients were from unrelated families with a mean age of 6.7 years (2.5-11) at the time of diagnosis with 4.8 mean years of delay in diagnosis. The most frequent clinical manifestations were recurrent respiratory infections and arthritis. In these patients, five previously reported mutations were found including four mutations (p.Q496X, p.Q497X, p.R520X, and p.R641H) in the Kinase domain besides one mutation (p.L37P) in the pleckstrin homology (PH) domain. Evaluations of KREC and TREC level in patients’ DBS showed low-to-undetectable copies of KREC (0-2 copies/3.2mm DBS) with normal copies of TREC. As patients with XLA have complete immunoglobulin defects and develop severe and recurrent infections, early diagnosis would be beneficial for the improvement of their quality of life. The study results may provide valuable information for the diagnosis, genetic counseling and prenatal diagnosis for the patients and their family members and emphasize performing KREC as an early diagnostic test in patients with XLA.

Background and aim: Standardized techniques help us to better diagnosis and follow up of allergic diseases. In this study, we determined the sensitivity, accuracy, and specificity of an Immunoblotting test compared to ImmunoCAP as the reference in vitro test for detection of specific IgE in allergic patients. Methods: In this cross-sectional study, specific IgE level was determined in patients with allergic symptoms who referred to the Immunology, Asthma and Allergy Research Institute, Tehran, Iran from 2010-2016, by two techniques. Eleven different allergens (six aeroallergens and five food allergens) were determined, and 303 specific IgE tests were performed for the patients by each method. The Immunoblotting test is a multiplex assay on a nitrocellulose membrane coated with 20 selected allergens. ImmunoCAP is considered as the reference method for determination of in vitro specific IgE. Its principle is an automated sandwich immunoassay, and allergens were bound to the solid phase, covalently. Finally, the fluorescence of elute was determined. Specific IgE more than 0.35 KU/L was considered as a positive test. Sensitivity, specificity, accuracy, kappa coefficient, positive and negative likelihood ratio (+/- LR), and correlation coefficient (calculated with Spearman test) between two tests were determined using statistical analysis (SPSS software, version 18). Results: One hundred and thirty five patients entered this study. The median age of the patients was 3.75 years with the males constituting 54.8% of the population. The most common cheif complaints were respiratory (51.6%), skin (41.8%) and gastrointestinal (27.9%) symptoms, respectively. The sensitivity, specificity, accuracy, +LR and -LR were 83%, 97%, 92%, 27.66 and 0.17, respectively. The kappa coefficient of the immunoblotting test was 0.81 compared to the reference technique. The correlation coefficient for positive tests between the two methods was 0.71 (p

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. Method name: Effect of airborne particulate matter on DNA methylation, Keywords: PM10 (PM with aerodynamic diameter ≤10 μm), Epigenetic, 5-Methylscytosine (5-mC), 5-Hydroxymethylscytosine (5-hmC), In vitro DNA methylation, Air pollution

Familial haemophagocytic lymphohistiocytosis (FHL) is a rare disorder of immune dysregulation. FHL inherited in an autosomal recessive pattern is classified into five subtypes based on underlying genetic defects. Mutations in four genes including PRF1, UNC13D, STX11 and STXBP2 are responsible for FHL2 to FHL5 respectively. The cause of FHL1 is associated with mutations in an unknown gene located at 9q21.3-22. This study aims to report the clinical features and genetic results of nine Iranian patients suffering from -haemophagocytic lymphohistiocytosis. Nine patients (five males and four females) suspected to FHL whose genetic evaluation of PRF1 and STX11 revealed no mutations, were entered the study to investigate UNC13D mutations. Primers were designed to amplify all coding regions and exon-intron boundaries of the gene. PCR products were then sequenced and analyzed by sequence analysis tools including BLAST. The most frequent clinical manifestations observed in the patients were fever and hepatosplenomegaly. In this study, five mutations were detected in UNC13D including four novel mutations (c.1434_1446delACCCATGGTGCAGinsTGGTGCT, c.1933C>T, c.1389+1G>C and c.2091+1G>A) besides to a previously reported deletion (c.627delT). The pathogenicity of the missense mutation was assessed using online prediction tools including SIFT and PolyPhen2. The study results may provide valuable information for genetic counseling especially for those who have a history of immunodeficiency diseases in their family and can be used for prenatal diagnosis.

Background: International guideline-recommended on-demand treatments for hereditary angioedema (HAE) include: C1-esterase inhibitor (plasma-derived or recombinant), or bradykinin-receptor antagonists. In most low- and middle-income countries (LMIC) these products are not registered or are unaffordable. Solvent-detergent, fresh or freeze-dried plasma therapy is thus the only available on-demand treatment in these settings; but published data on efficacy and safety are limited. This study evaluated the efficacy and safety of on-demand plasma treatment of acute HAE in two LMICs. Methods: A retrospective folder or patient registry review of acute swelling episodes necessitating emergency room attendance amongst known HAE patients was conducted at treatment centers in South Africa and Iran. Data collected included the site of angioedema, timing and amount of fresh frozen plasma (FFP) administered, time-to-resolution, hospital length of stay and adverse events. Results: There were 176 acute swelling episodes amongst 43 HAE patients; 98 were treated with FFP. The face, upper airway, and abdomen were involved in 15.3% (15/98), 53.1% (52/98) and 29.6% (29/98) of episodes treated with FFP respectively. Median (interquartile range ([IQR]) of FFP administered was 400 (280–560) mLs. In all episodes except two, FFP led to resolution, with median (IQR) hours to resolution 4 (2–12). Five transfusion reactions occurred, with one case of anaphylaxis and no deaths; giving an adverse reaction rate of 5%. Differences between South Africa and Iran included: (1) proportion of HAE type II(2) median (IQR) hours to FFP administration and hospitalization, (3) number of intubations after FFP infusion. Healthcare cost for FFP treatment was USD369- 791 in South Africa and USD275-550 in Iran, largely influenced by hospital length of stay. Conclusions: Plasma (fresh-frozen) remains the only available effective on-demand treatment for acute HAE in many countries. FFP is effective and safe, but time-to-resolution is slower and adverse events are more frequent than published data on targeted therapies. Overall healthcare cost of FFP approaches that of targeted therapies – now available through global access programs – when hospitalization is prolonged. Keywords: Hereditary angioedema, Fresh frozen plasma, Treatment

Chronic granulomatous disease (CGD) is a rare genetic disorder of neutrophil activity, resulting in increased rate of recurrent infections with catalase–positive bacteria and fungi, as well as various autoimmune diseases such as sarcoidosis, rheumatoid arthritis, and discoid and/or systemic lupus erythematosus. Few reports have reported lupus erythematosus (LE) in patients with X–linked CGD (XL-CGD) and carriers, and very few in autosomal recessive CGD (AR-CGD). Here, we present 5 patients with CGD developing LE at different ages to emphasize on the importance of appropriate follow–up and treatment in patients with CGD with clinical signs and symptoms of autoimmune diseases and even in those with negative serologic results.

In this study, we first tried to determine whether the expression level of 9 miRNAs in the peripheral blood CD8+ T cells of asthmatic patients varies from that of controls, and secondly, we investigated the effects of fluticasone furoate and vilanterol on the expression level of these miRNAs. Fifteen subjects including 8 healthy individuals and 7 asthmatic patients were included in this study. CD8+T cells were isolated from participants' peripheral blood by a negative selection method using magnetic-activated cell sorting (MACS). The expression of 9 miRNAs was examined between the healthy individuals and asthmatic patients. Then the expression level of 9 miRNAs before and after treatment with the drugs was examined by quantitative real-time PCR. No significant changes in the expression level of 9 miRNAs were observed in asthmatic patients compared to the healthy controls. Fluticasone and vilanterol, in combination, had the greatest effect on miRNA expression. MiR-150 and miR-106a were the most and the least miRNAs, respectively, present in CD8+ T cells of patients and controls. MiR-106a and miR-126 had a positive correlation in CD8+ cells of asthmatic patients. Although no significant difference in the expression level of studies miRNAs was observed, the correlations among miRNAs were significant. Therefore, we suggest that the correlation between miRNAs would be a very important factor in physiological and pathological conditions in healthy individuals and asthmatic patients. Such a miRNA-miRNA correlation network can be even more critical than any changes in the variation of their expression in the CD8+ T cells.

Assessment of the number of T-cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC) copies has been recently described as biomarkers of newly formed T and B cells respectively. In this study, we aimed to explore the effects of demographic variables including age, gender, weight, height and ethnicity on these two episomal DNA molecules. Second, for the first time in our country, we determined the reference values of TREC and KREC copy numbers in different age groups of Iranian healthy individuals as a threshold for identifying T cell and B cell lymphopenia. The TREC and KREC copy numbers were evaluated in 251 dried blood spot (DBS) samples from healthy volunteers (age range: 0-60 years). Six primary immunodeficiency (PID) patients were included as disease controls. TREC and KREC copies were markedly reduced with increasing age. Although the levels of TREC and KREC were higher in females than males, this difference did not reach statistical significance. These findings suggest that demographic variables including age should be considered for interpretation results of the TREC/KREC assay.

The Chronic granulomatous disease (CGD) is a primary immunodeficiency that characterized by mutations in phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, resulting in deficient antimicrobial activity of phagocytic cells and recurrent childhood infections. Hematopoietic stem cell transplantation (HSCT) is a curative option for patients with human leukocyte antigen (HLA) matched donor, when conventional cares and therapies fail. However, in many cases when the patients have not an HLA-matched donor, they need to a method to recapitulate the function of the affected gene within the patient’s own cells. Gene therapy is a promising approach for CGD. While, the success of retroviral or lentiviral vectors in gene therapy for CGD has been hampered by random integration and insertional activation of proto-oncogenes. These serious adverse events led to improvement and generations of viral vectors with increased safety characteristics. Gene therapy continues to progress and the advent of new technologies, such as engineered endonucleases that have shown a great promise for the treatment of genetic disease. This review focuses on the application of gene therapy for the CGD, the limitations encountered in current clinical trials, advantages and disadvantages of endonucleases in gene correction and modeling with CRISPR/Cas9 approach.

Background: Alteration of environmental factors and air pollution affects the trend of allergic diseases especially in cities such as Tehran. This study aimed to determine the prevalence of allergic rhinitis, conjunctivitis, atopic dermatitis and asthma among adults in the capital city of Iran. Methods: This cross-sectional study was performed between 2013 and 2016 in Tehran, Iran. The participants were adults between 18 and 45 yr of age. A specific questionnaire including demographic data and clinical symptoms was filled out by a trained interviewer. The diagnosis of allergic diseases was performed based on standard questionnaires and criteria. Results: The prevalence of allergic rhinitis, conjunctivitis, asthma and atopic dermatitis were 28.3%, 15.9%, 7.6% and 3.9%, respectively. Allergic rhinitis and conjunctivitis together were reported in 12.3% of the participants. Among patients with asthma, 47.4% had AR. Additionally, 25.7% of atopic dermatitis subjects were reported to have asthma. The subjects with at least one of these allergic diseases were 36.3%. Women showed a higher prevalence of allergic symptoms than men. There was a significant relationship between allergic symptoms and family history of atopic diseases. Conclusion: The most common allergic disease was allergic rhinitis. Regarding the comorbidity of asthma and allergic rhinitis, paying more attention to controlling these allergic diseases is deemed necessary.

Introduction: Airborne particles generate acute and chronic toxic effects on the human health. Cytotoxicity of air pollutants can be investigated through cytotoxicity assays. In this study, cytotoxicity of PM10 (particles ≤ 10 μm in diameter) from dust storm and inversion condition was compared through MTT assay on the human peripheral blood mononuclear cells (PBMCs) in vitro. Materials and methods: PM10 was sampled in Tehran, Iran, 2016, in dust storm and inversion. PBMCs were isolated from the whole blood sample through Ficoll - Hypaque gradient method. Cells were treated with two suspensions of the PM10 from dust storm and inversion at different concentrations (50, 100, 150, 200, 250, 300, 350 and 400 µg / mL) for 24 h. Cell viability was assessed by MTT test and reported in respect to the viability in untreated cells as negative control. Results: During the sampling period, June 6 and 12 - 15 November, 2016, were selected as the dusty and inversion days, respectively. Daily average PM10 in dust storm and inversion conditions were found of 220 and 345 µg / m3, respectively. Mean of viability in the PBMCs treated by the samples from dust storm and inversion was found 85.79 ± 9.97 % and 81.58 ± 11.72%, respectively. The cell viability values were obtained between 78 - 96 % for PM10 related dust storm condition and 70 – 92 % for PM10 sampled in inversion days. Conclusion: The results showed that the PM10 from dust storm as well as from inversion had the cytotoxicity effects on PBMCs. The particles related to the inversion caused toxic effects more than those from dust storm at all concentrations.

Allergic sensitization to inhalant allergens could be considered as a predictor in allergic diseases. The objective of this study was to assess IgE-mediated sensitization to inhalant allergens in allergic and non-allergic adults as well as the evaluation of its association with allergic diseases. This cross-sectional study was conducted from 2013 to 2016 in 604 allergic and 102 non-allergic adults selected from blood donor volunteers in Tehran, Iran. After taking informed consent, a standard questionnaire was filled to determine asthma, allergic rhinitis and/or conjunctivitis and atopic dermatitis in participants. Specific IgE assay to common inhalant allergens was performed for all subjects. Logistic regression analysis was used to evaluate the impact of IgE sensitization on allergic diseases. A total of 371(61.4%) allergic subjects and 41(40.2%) non-allergic patients were males. The weeds (especially saltwort) and grasses (particularly meadow fescue and ryegrass) were identified as the most common inhalant allergens. The prevalence of IgE sensitization to trees, weeds, and grasses was higher in subjects with allergic rhino-conjunctivitis and trees sensitization was a significant factor in them [OR=2.32, 95% CI (1.58-3.41)]. IgE sensitization to any inhalant allergens could be a predictor for allergic rhinitis, conjunctivitis and rhino-conjunctivitis in adults [OR=2.20, 95% CI (1.54-3.15], [OR=1.81, 95% CI (1.28-2.54)] and [OR=2.55, 95% CI (1.72-3.78)], respectively. With an increase in the sum of specific IgE concentrations, the prevalence of allergic conjunctivitis and rhino-conjunctivitis also increased. Our results showed the association between positive specific IgE and its concentration with some allergic diseases which could help physicians to prevent such diseases by recognizing and treating them, particularly in individuals with a positive family history of allergic diseases.

Background: Asthma is the first cause of children hospitalization and need for emergency and impose high economic burden on the families and governments. We aimed to investigate the economic burden of pediatric asthma and its contribution to family health budget in Iran. Methods: Overall, 283 pediatric asthmatic patients, who referred to two tertiary pediatric referral centers in Tehran capital of Iran, included from 2010-2012. Direct and indirect asthma-related costs were recorded during one-year period. Data were statistically analyzed for finding association between the costs and factors that affect this cost (demographic variables, tobacco smoke exposure, control status of asthma and asthma concomitant diseases). Results: Ninety-two (32.5%) females and 191(67.5%) males with the age range of 1-16 yr old were included. We found the annual total pediatrics asthma related costs were 367.97±23.06 USD. The highest cost belonged to the medications (69%) and the lowest one to the emergency (2%). We noticed a significant increasing in boys’ total costs (P=0.011), and 7-11 yr old age group (P=0.018). In addition, we found significant association between total asthma costs and asthma control status (P=0.011). Conclusion: The presence of an asthmatic child can consume nearly half of the health budget of a family. Our results emphasis on improving asthma management programs, which leads to successful control status of the disease and reduction in economic burden of pediatric asthma.

To determine the prevalence of allergic rhinitis (AR) among adult residents and investigate whether second-hand tobacco smoke (SHS) is correlated with AR as one of the global health problems and one of the most common respiratory disorders reducing the quality of life. A telephone interview survey was conducted by calling 16500 randomly selected telephone numbers from 22 regional telecommunications of Tehran (capital city of Iran) in 2010. A modified European Community Respiratory Health Survey (ECRHS) questionnaire was completed for adults aged between 20 to 44-year-old. Two questions about active smoking and being exposed to SHS were added to the questionnaire. five thousands five hundred cases (76.92%) responded to our calls among 7150 eligible telephone numbers. The gender of study population included 3412 female (62%) and 2088 male (38%) with the mean±SD age of 31.15±7.33. The prevalence of AR was 26.7%. There were no significant relationship between active smoking and AR; while a significant relationship was detected between SHS and AR among our participants (P=0.02). However, no significant difference was found between men and women. In addition, more than 50% of adults suffering from AR, showed significant symptoms of asthma (P

Aeroallergens play an important role in developing allergic diseases. The aim of this study was to determine the outdoor and indoor sensitization using a specific regional panel of aeroallergens in allergic patients. All patients with allergic symptoms referred to Immunology, Asthma and Allergy Research Institute (IAARI) in Tehran, Iran from December 2010 to July 2013 entered this cross sectional study. We evaluated serum samples for specific IgE against 20 selected aeroallergens provided by a specific panel (RIDA Allergy Screen test, IAARI panel). A p value less than 0.05 was considered as significant. The patients (n=602) were 49.8 % male and 50.2% female. The median age was 9 years. Positive specific IgE at least to one allergen was 53.2%. The percentages of patients with only outdoor or indoor sensitization were 37.5 and 19.7%, respectively. Moreover, 42.8% showed sensitization to both indoor and outdoor aeroallergens. The most common outdoor aeroallergens in decreasing order were plane tree (32.8%), Bermuda grass (32.2%), timothy grass (30.6%), saltwort (28.4%). The percentage of specific IgE to indoor allergens including mold and mite were 23.8 % and 22.2%, respectively. There was a statistically significant relationship between specific IgE to timothy grass and mold allergens between two genders (p=0.04 and p=0.02, respectively).The results of this study shows that outdoor aeroallergens can be considered as the most common causes of allergic symptoms in our allergic patients.

Current therapeutic approaches in allergic diseases especially asthma generally focus on using immunological strategies. According to the importance of FceRI in controlling allergic response we used two extracellular regions of Fc epsilon receptor I (FceRI) beta subunit peptides to design two peptide-based vaccines. Probably these peptides vaccines by triggering the immune response to FceRI can reduce the allergic symptoms through blocking the IgE specific receptor. Two extracellular parts of FceRI beta subunit were made by peptide synthesizer and conjugated with keyhole limpet Hemocyanin. These conjugated peptides were used and evaluated as therapeutic vaccines in allergic airway inflammation mouse model. Total IgE and anti ovalbumin specific IgE were measured in mice serum and compared in vaccinated and unvaccinated allergic mice. Histamine, prostaglandin D2 (PGD2), IL-4 and IL-13 were measured in bronchoalveolar lavage (BAL) fluid of vaccinated allergic mice versus unvaccinated and histopathologic examination were performed in studied groups. After vaccination of mice with each of the peptide vaccines the specific antibodies titer increased significantly in vaccinated groups versus unvaccinated. In histopathologic study, lavage eosinophil percentage and peribronchial inflammation in lung sections of vaccinated groups was decreased (p

Bee pollen grains, as the male reproductive part of seed-bearing plants contain considerable concentrations of various phytochemicals and nutrients. Since antiquity, people throughout the world used pollens to cure colds, flu, ulcers, premature aging, anemia and colitis. It is now well-documented that some bee pollen secondary metabolites (e.g. flavonoid) may have positive health effects. In recent years, the flavonoids have attracted much interest because of their wide range of biological properties and their beneficial effects on human health. The current review, points out potential therapeutic effects of bee pollen flavonoids as one of the main bee pollen bioactive compounds in allergic and immunological diseases. Due to the fact that some types of flavonoid components in bee pollen have anti-allergic, anti-oxidant and anti-inflammatory properties, bee pollen flavonoids can be excellent candidates for future studies including phytotherapy, molecular pharmacology and substitutes for chemicals used in treating allergic and immunological disorders.

Allergen-specific immunotherapy (AIT) has been recently considered as an alternative approach to ameliorate the symptoms of allergen exposure and improvement the patients’ quality of life. Dendritic cells (DC) in the forms of tolerogenic or Th1-induced cells have been investigated in several studies as one of the promising approaches of AIT in allergic diseases. The aim of this study was to evaluate the potency of casein-loaded DCs in eliciting the Th1 immune responses in Balb/c mice as a potential therapeutic approach in allergic condition. Immature bone marrow-derived DCs were loaded with casein (protein or mRNA) or green fluorescent protein (GFP) mRNA. DCs were evaluated based on the expression of specific markers and production of proinflammatory cytokines. Expression of DC markers in all groups was significantly higher than immature DCs, but lower than LPS-activated DCs. Despite an increase in TNF-α and IL-12, IL-6 was decreased in casein-DC treatments. Caseinloaded DCs could induce proliferation in lymphocytes and stimulate them to produce higher amounts of IFN-γ and in some extent IL-10 and TGF-β, while they could not stimulate IL-4 secretion. Casein-loaded DCs could partially elicit the Th1 responses; this would be a promising approach to use them as an allergic protective way for applying immune cell therapy in cow’s milk allergy.

Introduction: Air pollution is a serious health concern worldwide, accounting for high premature morbidity and mortality annually. In this article, we explain the framework of a series of interrelated researches for studying particulate matter (PM10, PM

Introduction: Astrocytes are the most abundant glial cell type. In addition to their neurological roles, astrocytes also have immune functions. They have been involved in antigen presentation in the central nervous system (CNS). Activated astrocytes express adhesion molecules, chemokines and release several inflammatory mediators, pro-inflammatory cytokines, neurotrophic and neuroprotective factors, thus these cells have a dual role within the CNS: neuroinflammation and repair processes. IL-19, IL-20, IL-22, IL-24, IL-26, IL-28A, IL-28B, and IL-29 are members of the IL-10 family of cytokines. These cytokines have different biological functions in spite of partial amino acid sequences homology. Signal transduction of the IL-10 family of cytokines is through R1-type and R2-type receptors. Methods: No information has been available about the expression and regulation of IL-19 in mice astrocytes and brain. To investigate the expression of IL-19, we examined its expression in C57BL/6 mice astroglial cells in response to lipopolysaccharide (LPS), using reversetranscription polymerase chain reaction (RT-PCR) method. Results: We provide for the first time, evidence that astrocytes can express IL-19 mRNA following LPS stimulation. Furthermore, we have found the expression of IL-19 mRNA in the cortex of adult C57BL/6 mice following intraperitoneal (i.p.) administration of LPS. Discussion: This finding will contribute to current knowledge on the function and behavior of cells and mediators during inflammatory conditions in the brain

Background: The prevalence of allergic diseases has risen in the last decades. The objective of this study was to determine the common allergens in children via the skin prick test. Methods: This cross-sectional study recruited 313 allergic children (4 months to 18 years old) referred to the Asthma and Allergy Clinic of Children’s Medical Center in Tehran. A questionnaire containing demographic data and patient history was completed. The Skin Prick Test (SPT) was selected according to the patients’ history of food and/or aeroallergen sensitivity. Results: Patients (62.4% male, 37.6% female) with symptoms of asthma (n=141, 57.1%), allergic rhinitis (n=50, 20.4%), atopic dermatitis (n=29, 11.7%), and urticaria (n=20, 8.1%) were studied. Positive skin prick test to at least one allergen was 58.1%. The most prevalent allergens were tree mix (26%), Alternaria alternata (26%), weed mix (23.6%), Dermatophagoides farinae (22.9%), Dermatophagoides pteronyssinus (22.9%), milk (21.7%), eggs (20%), and wheat flour (18.3%). Also, common allergens in the patients with different symptoms of allergic disorders were as follows: asthma (tree mix, weed mix, and Dermatophagoides farinae); allergic rhinitis (Dermatophagoides farinae, tree mix, and Dermatophagoides pteronyssinus); and atopic dermatitis (Alternaria alternata, Dermatophagoides pteronyssinus, and cockroaches). Conclusion: Identifying allergens in each area is necessary and has an important role in the diagnosis and management of allergic disorders and possibility of performing immunotherapy. In this study, the most common aeroallergens were tree mix, Alternaria alternata, and weed mix and also the most common food allergens were milk, eggs, and wheat. Considering these data, appropriate preventive strategies can decrease the cost and morbidity of therapeutic actions.

Background: Toluene diisocyanate (TDI) is an imperative chemical substance used in the production of polyurethane foams, elastomers, paints and coatings that cause a variety of health problems in workers who are exposed in work places. This study aimed to determine the asthma symptoms and serum specific IgE levels in TDI exposed workers and comparing the results with healthy control group.Methods: All the plants that use TDI in the manufacturing of paint and glue in the west of Tehran Province entered to the study and all the workers (550) completed modified initial questionnaire of the NIOSH, the questions were consisted of asthma symptoms. For each symptomatic exposed worker one healthy, sex and age matched control selected. Total IgE and Specific TDI IgE tests were done for each case and control groups.Results: Among 550 TDI exposed workers, 26(4.7%) had asthma symptoms. Nine (34.6%) of symptomatic workers who were exposed to TDI were active cigarette consumer versus 3(11.5%) unexposed workers, P=0.049(CI= 0.953-17.29) OR=4.059. Nine (34.6%) workers had positive family history of atopy versus 1(3.8%) unexposed workers, P=0.0138 (CI= 1.45-305.41) OR=13.24. TDI specific IgE was found in 2 TDI exposed workers and 1 unexposed worker (P=0.5). Mean of total IgE was 339.05 in exposed workers (P=0.201).Conclusion: This study provides clinical and paraclinical data of workers exposed to TDI and points to a relation between atopy and smoking habit with asthma symptoms that offer preventing recommendations for TDI exposed workers and their heath administrators.

Background: Exposure to some environmental agent such as different nutrition and contact with allergens may have a role in developing multiple sclerosis (MS). The present study was aimed to evaluate the cow′s milk allergy (CMA) in MS patients compared to healthy controls. Materials and Methods: Between March 2012 and July 2012, 48 MS patients were selected and compared with 48 healthy subjectsto assess the frequency of CMA in MS patients compared to healthy control.Cow′s milk specific immunoglobin E (IgE) was determined by Immuno CAP. Sex and the frequency of CMA were compared between study groups by Chi-square test. Results: Total of 96 subjects were assessed (22% male and 78% female). The mean age of the study subjects was 30.8 ± 6.6 years. Mean age of case and control groups was 30.7 (±6.9) versus 30.9 ± 6.3, respectively (P value = 0.83). There were no detection of cow′s milk specific IgE in serum of MS patients and healthy subjects. Conclusion: There was no difference between MS and healthy subjects regarding CMA.

Background: Immunotherapy with paternal lymphocytes plays an important role in preventing recurrent spontaneous abortion (RSA) and is an effective treatment for it. This kind of treatment is performed as an immunotherapy method in several centers in the world. It attributes to the production of anti-paternal cytotoxic antibodies (APCAs) in women with RSA. Production of APCA after lymphocyte immunotherapy (LIT) in RSA patients gives them a better chance for successful pregnancy. Regarding the important effect of trace elements on the function of the immune system, we tried to investigate the correlation between serum zinc level and the success of LIT in RSA. Materials and Methods: Serum zinc concentration was determined in two groups of RSA patients using atomic absorption spectrophotometer systems. Group (a) that responded to the paternal lymphocytes and their cross-match test was positive, and group (b) that had no response to the paternal lymphocytes immunizations and their cross-match test was negative. Results: Serum zinc levels in group (a) patients were 74.98 ± 11.88 μg/dl, which was significantly higher than those in group (b) with the zinc concentration of 64.22 ± 9.22 μg/dl. Conclusions: Zinc deficiency may be one of the substantial causes of negative results for LIT in RSA patients. Therefore, compensation of zinc defect before LIT can be a promising approach to improve the immune response in patients.

Background: The effect of nutrition in the course of multiple sclerosis (MS) is a topic of great interest. The present study was aimed to evaluate the immunoglobin E (IgE) against egg and fish in MS patients compared to healthy controls. Methods: Between March 2012 and July 2012, 48 MS patients were selected and compared with 48 healthy subjects to assess the frequency of IgE against egg and fish in MS patients compared to healthy control. Fish and Egg specific IgE was determined by Immuno CAP. Sex and the frequency of specific IgE were compared between study groups by Chi-square test. Results: Total of 96 subjects was assessed (22% male and 78% female). The mean age of the study subjects was 30.8 ± 6.6 years. Mean age of case and control groups was 30.7 (±6.9) versus 30.9 ± 6.3, respectively (P = 0.83). There were no detection of egg and fish specific IgE in serum of MS patients and healthy subjects. Conclusions: IgE allergy against fish and egg may be very unlikely to affect MS course.

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder due to a genetic defect in one of the components of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. This complex is composed of membrane-bound gp91-phox and p22-phox subunits, and cytosolic subunits consisting of p47-phox, p67-phox, and p40-phox. A mutation in CYBB gene encoding gp91-phox located on chromosome Xp21.1, leads to X-linked CGD. Herein, we report a 4-year-old Iranian boy presented with episodes of recurrent fever, cervical lymphadenopathy, and abdominal abscesses. Mutation analysis of the CYBB gene in the patient indicated a one-nucleotide deletion, c.316delT, resulting in p.W106GfsX.

Cow's milk allergy (CMA) is an immunological response to cow's milk proteins such as casein, α-lactalbumin and β lactoglobulin. The aim of this study was to determine the most common cow's milk allergenic proteins in patients with CMA and identify the most effective proteins in different allergic symptoms. Eighty seven patients (≤18 years) with allergy to cow’s milk from 2006 to 2013 entered this study. They had a positive history of allergic reactions to cow’s milk and a positive specific IgE test to whole cow's milk. The patients’ symptoms were divided into four groups. Serum specific IgEs against four different main proteins of cow's milk were measured using RIDA Allergy Screen. Among 87 patients, 53 (60.5%) were male and the median age was 2.5 years. The frequency of respiratory, skin, gastrointestinal symptoms, and anaphylaxis were 63.3%, 55.7%, 20.3%, and 13.4%, respectively. Specific IgEs to total cow's milk protein (n=75, 89.3%), and the main Cow’s Milk Proteins including α-lactalbumin (n=65, 77.4%), casein (n=64, 75.3%), β-lactoglobulin (n=52, 62.7%), and bovine serum albumin (n=35, 44.9%) were detected. Specific IgE tests to β-lactoglobulin were positive in 90% of the patients with anaphylaxis. Moreover, significant relationship was found between specific IgE to β-lactoglobulin and anaphylaxis (p=0.04). Although it is presumed that α-lactalbumin and casein are the most common allergenic proteins of cow's milk, in this study there is a significant relationship between the anaphylaxis and the presence of β-lactoglobulin-specific IgE. Therefore, more precautions are recommended due to possible anaphylactic reactions in patients with a positive test history for β-lactoglobulin specific IgE.

Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare inheritance syndrome, characterized by a disseminated infection with mycobacterium in children following BCG vaccination at birth. Regarding the vaccination program in Iran, it may consider as a public health problem. The pathogenesis of MSMD is dependent on either insufficient production of IFN-gamma (γ) or inadequate response to it. Here, we want to introduce three cases including two siblings and one girl from two unrelated families with severe mycobacterial infections referred to Immunology, Asthma and Allergy Research Institute (IAARI), from 2013 to 2015; their MSMD was confirmed by both cytokine assessment and genetic analysis. Regarding the clinical features of the patients, cell proliferation against a mitogen and BCG antigen was ordered in a lymphocyte transformation test (LTT) setting. ELISA was performed for the measurement of IL-12p70 and IFN- γ in whole blood samples activated by BCG + recombinant human IFN-γ and BCG + recombinant human IL-12, respectively. In contrast to mitogen, the antigen-dependent proliferation activity of the patients’ leukocytes was significantly lower than that in normal range. We identified a homozygous mutation in IL12RB1 gene for two kindred who had a homozygous mutation affecting an essential splice site. For the third patient, a novel frameshift deletion in IL12RB1 gene was found. The genetic study results confirmed the impaired function of stimulated lymphocytes to release IFN-γ following stimulation with BCG+IL-12 while the response to rhIFN-γ for IL-12p70 production was relatively intact. Our findings show that cellular and molecular assessments are needed for precise identification of immunodeficiency disorders especially those without clear-cut diagnostic criteria.

Mannose-binding lectin (MBL) is a protein of innate immune system that is involved in opsonization and complement activation. MBL deficiency is associated with predisposition to infectious diseases; however subnormal levels are also seen in healthy subjects. The aim of this study was to investigate the prevalence and clinical manifestation of MBL deficiency in patients with increased susceptibility to infection. We studied the MBL serum concentration of 104 patients with a history of recurrent and/or severe infections referred to Immunology, Asthma and Allergy Research Institute (IAARI) in order to evaluate the primary immunodeficiency (PID). The distribution of MBL deficiency in these patients and 593 healthy subjects of previous study were analyzed. The frequency of individuals with MBL deficiency was significantly higher in patients with recurrent and/or severe infections (13.5% [14/104]) compared with healthy subjects (4.7% [28/593]; p=0.001; OR 3.1, 95% CI 1.5-6.1). However, in 10.9% (7/64) of patients with recurrent infections without any immunodeficiency background, the MBL deficiency was detected. On the whole, our findings indicate an association between MBL deficiency and increased susceptibility to infections.

Background Anaphylaxis is an acute, systemic, and potentially fatal allergic reaction. Many things can cause anaphylaxis potentially but some agents are more common like some foods (milk, egg, soy, wheat, peanut, tree nut, shellfish, and fish), insect stings, medications, latex, and food-dependent exercise-induced anaphylaxis. The goal of this study is to show the common causes of anaphylaxis among the children with anaphylaxis history who were referred to the Immunology, Asthma and Allergy Research Institute (IAARI) during a 4-year period (2005-2009).Methods and Materials During those 4 years, we registered all children (

Context: Food allergy plays a significant pathogenic role among children with atopic dermatitis (AD).Objective: The aims of this study were to evaluate allergy to egg in these children and determine the egg specific immunoglobulin E (IgE) cutoff point.Design and Setting: It was a cross-sectional study that took place at Immunology, Asthma and Allergy Research Institute from 2005 to 2007.Methods: Children younger than 14 years old with AD entered the study. Careful medical histories were taken and skin prick and Immuno-CAP tests with the most commonly offending foods (cow's milk, egg, wheat, peanut, and soy) were performed. Children with a clear, positive history of food allergy and a positive IgE-mediated test or those with positive responses to both IgE-mediated tests were determined to have food allergies. The egg-specific IgE level cutoff point was determined.Results: A hundred patients entered the study (from 2 months to 12 years old). They were divided into 3 age groups: first

Objective: This study was performed to determine the immunophenotype of Megakaryocyte progenitor cells differentiated from UCB CD133+ and CD133− cells under the effects of interleukin–3 (IL–3), interleukin–6 (IL–6), stem cell factor (SCF) and thrombopoietin (TPO) in vitro.Materials and Methods: CD133+and CD133− cells were isolated by using CD133 isolation kit following the manufacturer’s instructions. Then, they were seeded in liquid serum free expansion mediums supplemented with the cytokine cocktail including IL–3, IL–6, SCF and TPO. The expression rate of CD34, CD41, CD61 and CD42b were measured on the days 0 and 7 of culture using flow cytometry. Student’s t–test was used for the comparisons and a p value less than 0.05 was considered to be significant.Results: Expressions of megakaryocytic markers on CD133+ cells were always higher than CD133− cells. CD133+ cells have higher potential of generating Mk colonies in vitro.Conclusion: CD133+ subset may be used as an alternative source for Mk progenitor cells production and these cells may improve platelet recovery after UCB transplantation.

Background: High prevalence and increasing rate of asthmatic patients around the word witnesses the high burden of asthma. We have limited data on asthma burden and economic costs in Iran. This study aimed to find direct and indirect economic costs of asthma and their association with some background factors in one of the referral tertiary centers for adult patients with asthma. Methods: We surveyed asthma related economic costs of 197 adult patients who referred to Milad Hospital, Tehran, Iran from Jun 2007 to January 2010. The patients were followed up for a period of one-year ±1 month and asthma related costs and its control status were registered. Results: Patients were consisted of 125 (64.1%) females and 70 (35.9%) males. Total cost of asthma was 590.22 ±32.18 USD for one patient per one year, the cost of drug, paraclinic, doctor visit, hospitalization, emergency, transportation, and absent days were 327.02, 4.76, 35.44, 3.82, 0.26, 113.03, 105.89 USD respectively. Men showed a significant elevation in their total (P=0.009) and drug costs (P=0.028). In addition, we found significant differences between total asthma costs and asthma control status (P=0.002). Conclusions: According to the high proportion of asthma, related cost compare to Total Income of an Iranian family, the necessity of public coverage of health assurance is quite clear. We suggest that improving asthma management and accessibility to specialized treatment centers can result in decreasing asthma medication and transportation costs as major direct and indirect asthma related costs.

Severe combined immunodeficiency (SCID) represents a rare group of primary immunodeficiency disorders (PIDs), with known or unknown genetic alterations. Here, we report a new interleukin 2 receptor, gamma chain (IL-2RG) mutation in an Iranian SCID newborn.The patient was a 6-day old boy with a family history of PID. The child was screened using a molecular-based analysis for the assessment of T cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs). Moreover, a complete immunological evaluation and gene sequencing was performed.Results showed undetectable TREC but a high level of KREC copy numbers. Flow cytometric data indicated low numbers of T and NK cells, but elevated number of B cells. A novel substitution in IL2RG: c.675 C>A, leading to p.225 Ser>Arg was found. Based on the functional analysis, the mutation is predicted to be damaging. The patient was diagnosed as a T B+ NK X-linked SCID.

Cytokines have been introduced as critical inducers in the development of Th subpopulations.Cytokines like IL-10 are involved in inducing regulatory T cells such as Type 1 regulatory T (Tr1) cells cells. IL-22 is a member of IL-10 family of cytokines, and IL-28A is a member of IFN-γ family. In this study, cord blood mononuclear cells (CBMC) from normal healthy individuals were isolated by Ficoll and then naïve T cells were purified by CD4+CD25+ Regulatory T cell Isolation kit. The effect of these two cytokines on production of IL-5, TGF-β, IL-10, IL-4 and IFN-γ cytokines from cord blood T cells was investigated to identify Tr1 cells as well as Th1 and Th2 polarization. Flow cytometric analysis showed that IL-28A and IL-22 were not effective in expression of IL-5 and TGF-β either alone or in synergy, but in view of IL-10, IL-4 and IFN-γ, the results showed that IL-22 increased IL-10 and IL-4 but had a decreasing effect on IFN-γ. The results showed that IL-28A was not effective in increasing or decreasing the level of IL-10, IL-4 and IFN-γ. Therefore, according to these results, IL-22 and IL-28A were not effective in inducing Tr1 cells.

Hyperimmunoglobulin E Syndrome (HIES) is a complex primary immunodeficiency characterized by both immunologic and non-immunologic manifestations. High serum IgE level, eosinophilia, eczema, recurrent skin and lung infections constitute the immunologic profile of HIES, whereas characteristic facial appearance, scoliosis, retained primary teeth, joint hyperextensibility, bone fractures following minimal trauma and craniosynostosis are the main non-immunologic manifestations. The diagnosis of HIES cannot be made by routine immunologic tests. As the main characteristic laboratory abnormalities of this syndrome are highly elevated serum IgE levels and eosinophilia; both features have a broad spectrum of differential diagnosis. The purpose of this essay was presenting the best way for diagnosis management of HIES. Based on the genetic reports of patients of the Center for Chronic Immunodeficiency (CCI) as a single center experience, and applying project management (PM) in health care research projects, we sought the best way for a rapid diagnosis of HIES. The combination of project management principles with immunologic and genetic knowledge to better define the laboratory and clinical diagnosis lead to an improvement of the management of patients with HIES. These results are shown in one "Decision Tree" which is based on 342 genetic reports of the CCI during the past ten years. It is necessary to facilitate the diagnostic analysis of suspected HIES patients; applying project management in health care research projects provides a better and more accurate diagnosis eventually leading to a better patients' care. This Abstract was presented at 16th Biennial Meeting of the European Society for Immunodeficiencies (ESID 2014), Prague, Czech Republic.

Introduction: The prevalence of allergic airway diseases has dramatically increased in recent years all over the world. Murine models of allergic airway inflammation have provided helpful information about treatment and cellular and molecular mechanisms of the disease. Previous published works using murine models to investigate latex allergy did not introduce a complete characteristic eosinophilic allergic airway inflammation. Latex allergy is important due to serious health impacts and widespread use of its products. Thus, the aim of this study was to establish a new mouse model of latex allergic airway inflammation using aerosol inhalation. Materials and Methods: Initially, four groups of mice were injected intraperitoneally (IP) with 0, 10, 50, or 200 µg of latex extract and their serum anti-latex IgE titers were compared using ELISA to find out the optimum dose for IP injection. In the second stage, a standard protocol of inhalation was designed and three doses of latex extract solutions including 1%, 0.1%, and 0.01% were used to induce allergic airway inflammation. Characteristics of this model were shown by studying different parameters including bronchoalveolar lavage (BAL), cytokines (Interleukin-5 [IL-5] and interleukin-13 [IL-13]) and serum anti-latex IgE and IgG1 titers by ELISA, specific histologic changes in the lung and eosinophilia of the bone marrow, peripheral blood, BAL, and lung inflammatory foci. Results: The aerosol inhalation of 1% latex allergens solution and pre-sensitization with 50 µg of latex in this study resulted in the development of characteristic allergic airway inflammation in BALB/c mice. These features included elevated allergen specific IgE and IgG1, peripheral blood, BAL and bone marrow eosinophilia and characteristic inflammatory response in lung with eosinophil infiltration. Elevated levels of IL-5 and IL-13 can be a sign of this type of inflammation. Conclusion: This paper describes a latex aerosol inhalational challenge model of eosinophilic airway inflammation in latex pre-sensitized BALB/c mice.