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Background: According to the WHO's recommendation for developing countries, Bacillus Calmette-Guerin (BCG) vaccination has been implemented in some countries as part of national vaccination programs at birth. Although it is generally considered safe, some complications may occur; including BCGitis (local) or BCGosis (systemic), ranging from mild like local abscesses to fatal impediments like osteomyelitis and disseminated BCG infection. This study aimed to determine the spectrum of inborn errors of immunity (IEI) in BCG-vaccinated neonates experiencing local or systemic complications., Methods: In this cross-sectional study, we investigated Iranian children referred to the Immunology, Asthma, and Allergy Research Institute (IAARI) between 2007-2023 for suspected immunodeficiency. Medical history was recorded, and primary screening tests for immunodeficiency were conducted for all cases. For suspected cases, more advanced immunologic investigations were performed to reach a definitive diagnosis. Furthermore, the study incorporated the documented genetic findings of the patients under investigation. All patients with inborn error of immunity who had a history of BCG vaccine complications within the first year of vaccination were enrolled in the study., Results: We investigated 3,275 cases suspected of IEI, identifying197 patients with both IEI and BCG vaccine complications. Among these, 127 (64.5%) were male. Symptoms began at or before 3 months of age in 64.8% of the cases, and parental consanguinity was reported in 79.2%. Genetic diagnoses were confirmed in 108 patients. Of the 197 patients, 108 (54.8%) had BCGitis, while 89 (45.2%) experienced systemic complications (BCGosis). A family history of IEI, BCG-related complications, and unexplained deaths were observed in 20.3%, 12.2%, and 29.9% of cases, respectively. Furthermore, 46.2% had at least one of these three risk factors in their history., Conclusions: Early BCG vaccine complications may indicate an underlying immunodeficiency, particularly when there is a positive family history of BCG complications, immunodeficiency, or unexplained deaths. Nation-wide vaccination protocols should address this issue by delaying inoculation to allow for immunological screening of suspected immunodeficient patients, thereby preventing BCG vaccine-related morbidity and mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fazlollahi, Goudarzi, Nourizadeh, Alizadeh, Tajik, Badalzadeh, Sarafzadeh, Mahlooji Rad, Adab, Moradi, Razaghian, Sabetkish, Pourpak and Moin.)

Background: Primary immunodeficiency diseases (inborn errors of immunity) with partial albinism are a group of autosomal recessive syndromes including Chediak Higashi Syndrome (CHS), Griscelli Syndrome type 2 (GS2), Hermansky-Pudlak Syndromes type 2 and 10 (HPS2, HPS10), Vici syndrome and P14/LAMTOR2 deficiency., Methods: Twenty-five patients including 10 CHS, 10 GS2, and 5 HPS2 were evaluated in this study within the last 10 years. Five cases with oculocutaneous albinism (OCA) and 5 healthy subjects without albinism were used as two control groups. Genetic analyses were performed by whole exome or panel sequencing or targeted Sanger sequencing. Subsequently, leukocyte granules in peripheral blood smear and hair shaft were examined as screening tests., Results: Giant granules were only presented in the leukocytes cytoplasm of 10/10 CHS patients. The uneven cluster of pigments and giant melanin granules in hair samples were observed in 10/10 GS2 and 10/10 CHS patients, respectively. In both 5/5 OCA and 5/5 HPS2 patients, there were regular pigments in the middle of hair shafts. Genetic analyses were performed for all patients, revealing 7 novel variants in LYST gene for CHS patients and 4 novel variants in AP3B1 for HPS2 patients., Conclusion: Receiving hematopoietic stem cell transplantation (HSCT) in a timely manner is crucial in CHS and GS2 patients; therefore, screening tests may provide a vital clue for early diagnosis in these patients. However, the final confirmation of CHS, GS2, and HPS2 disorders is done by genetic assay., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

The purpose of this study is to investigate the effect of air pollutants and noise on the prevalence of childhood asthma in Tehran, Iran. The standardized questionnaire was completed by one of the parents of children aged 6-7 years or by adolescents aged 13-14 years. The asthma prevalence in ages 6-7 and 13-14 was found to be 8.8% and 17.44%, respectively. A significant positive association was observed between "ever wheezing" and monoxide carbon (CO) concentration (OR=1.84, 1.05-3.25 in 13-14 years), the occurrence of 4 to 12 wheezing attacks and sulfur dioxide (SO2) concentration (Odds Ratio (OR)=1.39, 1.04-1.91) and particulate matter less than 2.5 micron (PM2.5) concentration (OR=1.38, 1.05-1.98 and OR=1.13, 0.98-1.39 in 6-7 and 13-14 years, respectively), as well as one night per week of sleep disturbances and nitrogen dioxide (NO2) concentration (OR=1.09, 1.03-1.16 in 6-7 years, respectively). It was also found that there was a significant interaction between the noise level and particulate matter less than 10 micron (PM10) level. Based on the findings, exposure to certain outdoor air pollutants and noise can affect prevalence of asthma symptoms in residence of Tehran. The simultaneous presence of air pollutants and noise has an aggravating effect on the prevalence of asthma symptoms. Therefore, controlling sources of pollutants for reducing asthma symptoms is suggested.

Background: In order to support the comprehensive classification of Leukocyte Adhesion Deficiency-I (LAD-I) severity by simultaneous screening of CD11a/CD18, this study assessed clinical, laboratory, and genetic findings along with outcomes of 69 LAD-I patients during the last 15 years., Methods: Sixty-nine patients (40 females and 29 males) with a clinical phenotype suspected of LAD-I were referred to Immunology, Asthma, and Allergy research institute, Tehran, Iran between 2007 and 2022 for further advanced immunological screening and genetic evaluations as well as treatment, were enrolled in this study., Results: The diagnosis median age of the patients was 6 months. Delayed umbilical cord separation was found in 25 patients (36.2%). The median diagnostic delay time was 4 months (min-max: 0-82 months). Forty-six patients (66.7%) were categorized as severe (CD18 and/or CD11a: below 2%); while 23 children (33.3%) were in moderate category (CD18 and/or CD11a: 2%-30%). During the follow-ups, 55.1% of children were alive with a mortality rate of 44.9%. Skin ulcers (75.4%), omphalitis (65.2%), and gingivitis (37.7%) were the most frequent complaints. Genetic analysis of the patients revealed 14 previously reported and three novel pathogenic mutations in the ITGB2 gene. The overall survival of patients with and without hematopoietic stem cell transplantation was 79.3% and 55.6%, respectively., Conclusion: Physicians' awareness of LAD-I considering delayed separation of umbilical cord marked neutrophilic leukocytosis, and variability in CD11 and CD18 expression levels, and genetic analysis leads to early diagnosis and defining disease severity. Moreover, the prenatal diagnosis would benefit families with a history of LAD-I., (© 2023 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Griscelli syndrome type 2 (GS2) is an autosomal recessive immunodeficiency characterized by hair hypopigmentation, recurrent fever, hepatosplenomegaly and pancytopenia. This study aims to find new genetic changes and clinical features in 18 children with GS2 caused by the RAB27A gene defect. In all, 18 Iranian children with GS2 who presented with silver grey hair and frequent pyogenic infection were included in this study. After recording demographic and clinical data, PCR sequencing of the RAB27A gene was performed for all exons and exon-intron boundaries. Two patients in this study were subjected to whole-exome sequencing followed by Sanger sequencing. Light microscopy study of hair showed large irregular clumps of pigment with the absence of giant granules on the blood smear. Mutation analysis of the RAB27A gene identified two novel missense mutations as homozygous in a patient, one in exon 2, c.140G>C and another in exon 4, c.328G>T. In addition, for 17 other patients, 6 reported mutations were obtained including c.514_518delCAAGC, c.150_151delAGinsC, c.400_401delAA, c.340delA, c.428T>C and c.221A>G. The mutation c.514_518delCAAGC was the most frequent and found in 10 patients; this mutation may be considered a hotspot in Iran. Early diagnosis and treatment of RAB27A deficiency can contribute to better disease outcomes. In affected families, genetic results could be urgently needed to make a timely decision about haematopoietic stem cell transplantation and prenatal diagnosis., (© 2023 The Scandinavian Foundation for Immunology.)

Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-α/β (underlying viral diseases in the patients) and to IL-12 and IL-23 (underlying mycobacterial diseases). Cells homozygous for the common P1104A TYK2 allele have selectively impaired responses to IL-23 (underlying isolated mycobacterial disease). We report three new forms of TYK2 deficiency in six patients from five families homozygous for rare TYK2 alleles (R864C, G996R, G634E, or G1010D) or compound heterozygous for P1104A and a rare allele (A928V). All these missense alleles encode detectable proteins. The R864C and G1010D alleles are hypomorphic and loss-of-function (LOF), respectively, across signaling pathways. By contrast, hypomorphic G996R, G634E, and A928V mutations selectively impair responses to IL-23, like P1104A. Impairment of the IL-23-dependent induction of IFN-γ is the only mechanism of mycobacterial disease common to patients with complete TYK2 deficiency with or without TYK2 expression, partial TYK2 deficiency across signaling pathways, or rare or common partial TYK2 deficiency specific for IL-23 signaling., (© 2022 Ogishi et al.)

Background: An increasing interest in the field of molecular diagnosis of allergy has been developed in recent years and it goes to be as the routine in vitro protocol in allergy diagnosis. friendly allergen nano-bead array (FABER) is a new multiplex assay for the evaluation of specific IgE against 244 allergens including whole extracts and allergenic molecules. The research intended to assess the pattern of IgE sensitization to allergenic components of allergens in allergic adults using FABER 244., Methods: Sixty patients with allergic diseases entered this cross-sectional study. Specific IgE to 122 whole allergens extracts and 122 allergenic components were assessed using an allergen nano-bead array (FABER) for all patients. This test includes inhalant and food allergens., Results: Thirty-seven patients were male (61.7%). The mean (SD) age of patients was 30.73(±6.87) years. As the allergen nano-bead array results showed, Lolium perenne (63.3%), Phleum pratense (60%) and Platanus acerifolia (51.7%) were considered as the most common IgE sensitizations to the aeroallergen extracts. Moreover, Lol p 1, Phl p 1.0102 and Cup a 1 were found as the most frequent allergenic components in our allergic patients. Among protein families, CCD-bearing proteins, expansin, cysteine protease and profilin families illustrated the highest allergic sensitization., Conclusions: The results of the present study demonstrated that despite the higher prevalence of sensitization to Salsola kali (47.2%) using extract-based assays in the previous phase of this research, allergenic components of grasses (Lol p 1, Phl p 1.0102), Cup a 1 as well as Sal k1 as the major components of Cupressuss arizonica and Salsola kali showed the higher sensitization, respectively, in adults' allergic patients using FABER test., (© 2022 John Wiley & Sons Ltd.)

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).

Noise has been reported as one of the most important risk factors for asthma, but there are some disagreements. This study aimed to investigate the effect of road noise on asthma prevalence in adults. In the current study, 3172 adults were interviewed through the ECRHS standardized questionnaire in Tehran, the capital of Iran. Exposure to road noise was assessed considering distance of individual participants from the noise monitoring stations via the spatial analysis in GIS software. Logistic regression was used to assess the effect of noise on the symptoms of asthma. Findings showed a significant positive association between wheezing with dyspnea as the best marker for asthma and noise levels at daytime (OR 1.03; 0.98-1.05) and nighttime (OR 1.05; 0.84-1.09). Also, a significant positive association was obtained between daytime and nighttime noise levels and other asthma symptoms including wheezing, nocturnal chest tightness, nocturnal dyspnea, wheezing without cold, nocturnal cough, and asthma medication. Association between current asthma and noise level was not significant. There was a significant association between population age and current asthma prevalence (P = 0.001). Therefore, chronic exposure to road noise especially in the nighttime could increase asthma prevalence. So, control of noise sources can be suggested to diminish asthma in adults., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Hereditary Angioedema (HAE) is a rare autosomal dominant immunodeficiency disease with mutation in C1 inhibitor gene ( SERPING1 ) which deficient and dysfunction of C1-INH protein result in HAE type I or type II, respectively. The present study aimed to define the genetic spectrum of HAE type I and type II among Iranian patients., Methods: Thirty-four patients with clinical phenotype of recurrent edematous attacks in face, upper and lower limbs, hands, and upper airway entered the study. Mutations in SERPING1 were analyzed using PCR and Sanger Sequencing. In addition, Multiplex Ligation-dependent Probe Amplification (MLPA) was performed to discover large deletions or duplications in negative screening samples by Sanger., Results: Twenty-three patients were diagnosed with HAE type I and 11 with HAE type II. Fourteen distinctive pathogenic variations including five frameshift (p.G217Vfs*, p.V454Gfs*18, p.S422Lfs*9, p.S36Ffs*21, p.L243Cfs*9), seven missense (p.A2V, p.G493R, p.V147E, p.G143R, p.L481P, p.P399H, p.R466C), one nonsense (p.R494*), and one splicing defect (C.51 + 2 T˃C), which three of these mutations were identified novel. However, no mutation was found in seven patients by Sanger sequencing and MLPA., Conclusion: Final diagnosis with mutation analysis of HAE after clinical evaluation and assessment of C1INH level and function can prevent potential risks and life-threatening manifestations of the disorder. In addition, genetic diagnosis can play a significant role in facilitating early diagnosis, pre-symptomatic diagnosis, early diagnosis of children, asymptomatic cases, and those patients who have the borderline biochemical results of C1-INH deficiency and/or C4.

Purpose: This study aimed to determine the impact of MI on self-efficacy, beliefs about medicines and medication adherence among adolescents with asthma., Method: This randomized controlled trial conducted on 52 adolescents with asthma referring to the Pediatric Medical Center in Tehran, Iran. They were randomly assigned to the control and intervention groups. The educational intervention consisted of 3 one-hour sessions per week, which was held individually in the areas of medication adherence, beliefs about medicines and self-efficacy. Four validated questionnaires including demographic characteristics, medication adherence, self-efficacy and beliefs about medicines were completed by self-report both before the MI and 40 days after the end of the intervention., Results: In the baseline, the two groups were homogeneous in terms of demographic characteristics and outcome measures. At the post-test, the mean scores of the three outcome measures in the intervention group were reported higher compared to the scores in the control group (p < 0.05). The difference between the mean scores in medication adherence, beliefs about medicines and self-efficacy in the post-test between the two groups, even with the elimination of the effect pre-test scores, were significant (p < 0.05)., Conclusions: The results of this study showed that MI can be effective in improving medication adherence, beliefs about medicines, and self-efficacy., Practice Implications: The primary goal in the treatment of patients with asthma is asthma control by using corticosteroids. MI is one of the interventions that can simultaneously provide motivation, readiness, beliefs about medicine and self-efficacy for behavioral changes (medication adherence) in patients with asthma., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Competing Interests: IAgache is an Associate Editor Allergy and CTA. CA reports grants from Allergopharma, grants from Idorsia, Swiss National Science Foundation, Christine Kühne‐Center for Allergy Research and Education, European Commission's Horison's 2020 Framework Programme, Cure, Novartis Research Institutes, Astra Zeneca, scibase, advisory role in Sanofi/Regeneron, grants from Glakso Smith‐Kline, advisory role in scibase. IA reports personal fees from Hikma, Roxall, Astra Zeneca, Menarini, UCB, Faes Farma, Sanofi, Mundipharma, Bial, Amgen, Stallergenes. SBA reports grants from TEVA, personal fees from TEVA, AstraZeneca, Boehringer Ingelheim, GSK, Sanofi, Mylan. VC reports personal fees from ALK, Allergy Therapeutics, LETI, Thermofisher, Merck, Astrazeneca, GSK. TC reports grants and personal fees from Stallergenes. PD reports personal fees from ALK‐Abello, Stallergenes‐Greer, Astra Zeneca, GlaxoSmithKline, Mylan, Sanofi. SD reports personal fees and non‐financial support from ALK Abello, personal fees from Adiga, Biomay, Allergopharma, Anergis, Allergy Therapeutics. TH reports personal fees from GSK, Mundipharma, Orion Pharma. SH reports other from ALK‐Abelló, other from ALK‐Abelló. EH reports personal fees from Sanofi, Novartis, GSK, AstraZeneca, Circassia, Nestlè Purina. JCI reports personal fees from Faes Farma, Laboratorios Casasco Argentina, Abbott de Ecuador, EuroFarma Argentina. MJ reports personal fees from ALK‐Abello, Allergopharma, Stallergenes, Anergis, Allergy Therapeutics, Circassia, Leti, Biomay, HAL, during the conduct of the study; personal fees from Astra‐Zeneka, GSK, Novartis, Teva, Vectura, UCB, Takeda, Roche, Janssen, Medimmune, Chiesi,. LK reports grants and personal fees from Allergopharma, MEDA/Mylan, LETI Pharma, Sanofi, grants from Stallergenes, Quintiles, ASIT biotech, grants from ALK Abelló, Lofarma, AstraZeneca, GSK, Inmunotk, personal fees from Allergy Therapeut., HAL Allergie, Cassella med; and Membership: AeDA, DGHNO, Deutsche Akademie für Allergologie und klinische Immunologie, HNO‐BV, GPA, EAACI. PK reports personal fees from Adamed, Berlin Chemie Menarini, Boehringer Ingelheim, AstraZeneca, Lekam, Novartis, Polpharma, GSK, Polpharma, Sanofi, teva. VK reports other from GSK, non‐financial support from Mylan, AstraZeneca, Dimuna, Norameda. SL reports personal fees from DBV, Sanofi Aventis, Allergopharma, ALK, Nutricia, Bencard. EM reports personal fees from Sanofi, Novartis, AstraZeneca and Chiesi. JM reports personal fees and other from SANOFI‐GENZYME & REGENERON, NOVARTIS, ALLAKOS, MITSUBISHI‐TANABE, MENARINI, UCB, ASTRAZENECA, GSK, MSD, grants and personal fees from MYLAN‐MEDA Pharma, URIACH Group. MO reports personal fees from Hycor Diagnostics, Thermo Fisher Phadia. YO reports personal fees from Torii Pharmaceutical Co., Ltd., Shionogi Pharmaceutical Co.,Ltd. OP received research grants from Inmunotek S.L., Novartis and MINECO and has received fees for giving scientific lectures or participation in Advisory Boards from: Allergy Therapeutics, Amgen, AstraZeneca, Diater, GlaxoSmithKline, S.A, Inmunotek S.L, Novartis, Sanofi‐Genzyme and Stallergenes. NGP reports personal fees from Novartis, Nutricia, HAL, MENARINI/FAES FARMA, SANOFI, MYLAN/MEDA, BIOMAY, AstraZeneca, GSK, MSD, ASIT BIOTECH, Boehringer Ingelheim, grants from Gerolymatos International SA, Capricare. OP reports grants and personal fees from ALK‐Abelló, Allergopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, Lofarma, ASIT Biotech Tools S.A., Laboratorios LETI/LETI Pharma, Anergis S.A., Glaxo Smith Kline, grants from Biomay, Circassia, Pohl‐Boskamp, Inmunotek S.L., personal fees from MEDA Pharma/MYLAN, Mobile Chamber Experts (a GA2LEN Partner), Indoor Biotechnologies, Astellas Pharma Global, EUFOREA, ROXALL Medizin, Novartis, Sanofi‐Aventis and Sanofi‐Genzyme, Med Update Europe GmbH, streamedup! GmbH, John Wiley and Sons, AS. DPreports grants and personal fees from GlaxoSmithKline, personal fees from Menarini, Pliva, Belupo, AbbVie, Novartis, MSD, Chiesi, Revenio, personal fees and non‐financial support from Boehringer Ingelheim, non‐financial support from Philips. MR is on the Advisory board‐ A. Menarini ‐ Speaker ‐ Astra Zeneca, Novartis, Sanofi, Mylan. FSRreports speaker and advisory fees from AstraZeneca, Novartis, Sanofi, GSK, Teva and Lusomedicamenta. GR reports payment to his Institution from Allergo Pharma. BSreports personal fees from Allergopharma, during the conduct of the study; grants from National Health Programm, grant, personal fees from Polpharma, ASTRA, personal fees from Mylan, Adamed, patient ombudsman, national Centre for Research and Development, Polish Allergology Society. JS reports grants and personal fees from Sanofi, personal fees from GSK, Novartis, Astra Zeneca, Mundipharma, Faes Farma. GS reports personal fees from ALK, and leds on the BSACI Rhinitis Guidelines and lead for EUFOREA on Allergic Rhinitis. PSG reports personal fees from Allergopharma, ALK, grants from Bencard, grants and personal fees from Stallergenes. JS reports personal fees from Mylan, F2F events. ATB reports grants and personal fees from Teva, AstraZeneca, GSK Sanofi, Mundipharma, personal fees from Bial, Novartis. MJTreports grants from European Commission, SEAIC, ISCIII, personal fees from Diater laboratory, Leti laboratory, Aimmune Therapeutics. MW reports personal fees from ALK‐Abello, Allergopharma, AstraZeneca, Bencard, Genzyme, GlaxoSmithKline, HAL Allergy, LETI, Meda Pharma, Novartis, Sanofi, Stallergenes, Teva. DW reports other from Optinose, ALK, Sanofi; past Co‐Chair of the Joint Task Force on Practice Parameters of the AAAAI and ACAAI. Second author of a recently published practice parameter on Rhinitis. MW reports other from Aralez (Medexus), Pediapharm, Pfizer, Astra Zeneca, GSK, Alk. MZ reports personal fees from Takeda. TZ reports and Organizational affiliations: Commitee member: WHO‐Initiative “Allergic Rhinitis and Its Impact on Asthma” (ARIA). Member of the Board: German Society for Allergy and Clinical Immunology (DGAKI). Head: European Centre for Allergy Research Foundation (ECARF). Secretary General: Global Allergy and Asthma European Network (GA2LEN). Member: Committee on Allergy Diagnosis and Molecular Allergology, World Allergy Organization (WAO). FIGURE 1Countries with Pocket Guide membersFIGURE 2Proposed Flow of Precision Medicine approach in allergic diseases. *examples of exceptions: Thunderstorm‐induced asthma, patient with moderate rhinitis and severe asthma during pollen seasonFIGURE 3Treatment algorithm using visual analogue scale (VAS) for adolescents and adults AIT, allergen immunotherapy; VAS, visual analogue scale.FIGURE 4Algorithm for AIT in asthma

Exosomes are extracellular vesicles that are involved in intracellular communication and different biological processes. Recently, the importance of microRNAs (miRNAs) in exosomes has been considered as biomarkers in asthma diagnosis. This study aimed to determine the expression of selective miRNAs from plasma-derived exosomes in moderate and severe asthmatic patients compared with healthy controls. Forty-six subjects including 22 patients with severe and mild to moderate allergic asthma and 24 healthy controls have entered this study. MiRNAs were extracted from the plasma exosomes and selective miRNAs (miR-21, miR-16, miR-Let7, miR-148a, miR-155, miR-125, miR-150, miR-146a, miR-223, miR-126) expressions levels were determined; using quantitative polymerase chain reaction (qPCR). In this study, we found a significant up-regulation of miR-223 and miR-21 in moderate asthmatic patients compared to the healthy controls (p=0.002, p=0.006). MiR-223 and miR-21 had the probability of 83% and 76% diagnosis estimation in moderate asthmatic patients respectively. Therefore, they could be used as biomarkers in these patients.  No expression of miR-125, miR-126, and miR-155 was found in plasma exosomes by qPCR in this study. The other miRNAs had no significant expression between different groups. Based on our findings,miR-223 and miR-21 may be considered biomarkers or used for targeted immunotherapies in asthma.

The skin prick test (SPT) could be applied as a useful in vivo method for the detection of sensitization in epidemiological and diagnostic studies if the wheal size is ideally evaluated. We focused on SPT wheal size to identify sensitization pattern to common inhalant and food allergens. In this cross-sectional study, SPT results were obtained from a total of 972 allergic patients. Common allergen extracts for SPT were selected according to the type of allergic diseases, and the geographical pattern. SPT with food allergens was performed for patients with atopic dermatitis (AD) and chronic urticaria (CU). A total of 461 male (47.4%) and 511 female (52.6%) participated in this study (median age: 31 years). The majority of individuals were affected with allergic rhinitis (AR) (n = 624) and asthma (n = 224); while 129 and 67 patients suffered from AD and CU, respectively. The most common aeroallergens were Russian thistle (52.1%) and lamb's quarter (50.7%) with the largest wheal diameter. The wheal size of lamb's quarter was significantly different between patients with asthma and AR (P<.001). In addition, a significant difference was detected in wheal diameter in response to the Russian thistle between patients with AR and AD (P = .001). Shrimp (23.6%) and Peanut (22.5%) caused the most common food sensitization in patients with AD and CU. Having in mind the most common weed pollens including the Russian thistle and lamb's quarter, preventive strategies, such as, removing unwanted weeds or preventing them from growing, avoidance, and specific immunotherapy may be crucial for better disease control., (© 2020 Wiley Periodicals LLC.)

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.

Background: The medical profession has always been an inspiration for human societies throughout its diverse history. This position and historical authority in the field of ethics has had a different and higher status, in such a way that many of the norms of general ethics and professional ethics, especially principles, such as trust, confidentiality and respect for human dignity, have been developed by medical professionals. Developing guidelines of general and professional ethics is one of the inherent duties of the Medical Council of the Islamic Republic of Iran (IRIMC) as a professional organization. In this regard, the Supreme Council of IRIMC has approved the "Code of Ethics for Medical Professionals" and, in accordance with its legal authority, has annexed it to the disciplinary regulations of IRIMC., Methods: A draft document, the result of extensive literature review, was discussed in 27 expert panel meetings and after receiving and endorsing the stakeholders' point of view, was approved by the IRIMC Supreme Council., Results: The first edition of "Code of Ethics for Medical Professionals, Medical Council of Islamic Republic of Iran" was developed on July 6, 2017 by the Supreme Council of IRIMC. The guideline was set to take effect one year after its enactment. The first edition was revised and completed and final edition was adopted on August 9, 2018 by IRIMC in 13 chapters and 140 articles (original full text is available in the Supplementary file 1)., Conclusion: According to the approved decision by the Supreme Council of IRIMC on May 10, 2018, the final edition takes effect as of October 7, 2018., (© 2020 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

In light of various supports of prodigious figures in the field of immunology and allergy, the subject area has been faced a great leap during the last century. The current state of the discipline owes an abundant appreciation for the scholars motivated in escalating the true nature of the science, who left no stone unturned in improving the general common sense and understanding of the human knowledge in general, and immunology and allergy in particular. Professor Reza Farid Hosseini is among the dignitaries who invested his life and energy on weaving the tapestry of the immunology and allergy. He delivered a great deal of influence on the field by his ethical devotion to science and was a significant contributor in the realms of the human immune system. His presence drastically rehabilitated the place of the Immunology in Iran, and the current paper seeks to review the personal and academic life of Professor Reza Farid Hosseini in honor and appreciation for his in-depth involvement in the field. The paper summarizes Professor Farid's childhood, school, and higher education, compilations, and translation of books, his contribution to the research both inside and outside of Iran, and scientific activities of Dr. Farid Hosseini.

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The advances in science and technology in recent decades, especially in medical sciences, have raised new ethical challenges. Hence, professional organizations in the field of medical science are trying to develop regulations in the field of medical ethics to help medical science professionals in making the best decisions in different circumstances and moral dilemmas. The organizations also try to monitor their performance using those regulations. On the other hand, due to the specialization of medical science as well as the complexity of communication between these disciplines, there is a growing need for regulations to answer questions and resolve the challenges of each discipline. Certainly, scientific societies, due to benefit from relevant specialists, are the best reference for the development of specialized guidelines, one of which is the Iranian Society of Asthma and Allergy (ISAA). The aim of the current study was to develop codes of ethics for ISAA members, using a qualitative study. Generally, the ISAA codes of professional ethics consists of general and specific sections. In order to compile the general section, the upstream medical documents, including the patients' rights charter in Iran, the research ethics guidelines approved by the Ministry of Health and Medical Education (MOHME), ethical codes from the international societies of asthma and allergy, the general codes of professional ethics of the Iran Medical Council and the Islamic jurisprudential rules and the statute law of the country were used. To develop specific sections, we interviewed the experts in the field of Asthma and Allergy about the ethical challenges they had ever faced with. The ISAA codes of professional ethics developed in five chapters, entitled "Ethical Guidelines for the Mangers and Director of the Society, General Guidelines, Specific Guidelines, Ethical Guidelines for Research and Education, and Procedure for Supervision on the Professional Behavior of the ISAA Members", and approved by the board of directors of ISAA.

Asthma is a complex disease with diverse clinical manifestations ranging from mild to severe. Despite existing guidelines for asthma recognition and treatment, still a proportion of patients stay uncontrolled. Combinational therapy which comprises inhaled corticosteroids (ICS) and a long acting B2 adrenreceptor agonist (LABA) has been suggested to control asthma. In this study T-bet expression was attested in CD4 T cells treated with Fluticasone Furoate (FF), Vilanterol (V) and FF/V combination in severe asthmatic patients compared to patients with moderate asthma and healthy controls using Immunocytochemistry (ICC). First, CD4 T cells were isolated from PBMCs of 12 patients and controls using CD4 T cell isolation kit. Subsequently, isolated CD4 T cells were cultured with FF, V and FF/V for 1 h. To accomplish ICC, cells were incubated with anti-T-bet antibody, and then stained with HRP-bound secondary antibody. T-bet expression was evaluated using light microscopy. Statistical analyses were performed using R 3.5.2 software and visualized by ggplot2 3.1.0 package. Significant increasing in T-bet expression was seen in CD4 T cells from patients with moderate asthma treated with FF and FF/V. Suggesting conclusion would be distinct mechanisms responsible for severe asthma and moderate asthma in the patients and the needs for novel therapies. Further molecular studies in different asthma phenotypes would be instructive for asthma treatment., (Copyright © 2020. Published by Elsevier Ltd.)

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&#95;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.

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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.

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.

Purpose: Mendelian susceptibility to mycobacterial disease (MSMD) is a rare primary immunodeficiency, triggered by non-tuberculous mycobacteria or Bacillus Calmette-Guérin (BCG) vaccines and characterized by severe diseases. All known genetic etiologies are inborn errors of IFN-γ-mediated immunity. Here, we report the molecular, cellular, and clinical features of patients from 15 Iranian families with disseminated disease without vaccination (2 patients) or following live BCG vaccination (14 patients)., Methods: We used whole blood samples from 16 patients and 12 age-matched healthy controls. To measure IL-12 and IFN-γ, samples were activated by BCG plus recombinant human IFN-γ or recombinant human IL-12. Immunological assessments and genetic analysis were also done for the patients., Results: Eight patients affected as a result of parental first-cousin marriages. Seven patients originated from multiplex kindred with positive history of death because of tuberculosis or finding the MSMD-related gene mutations. Two patients died due to mycobacterial disease at the ages of 8 months and 3.7 years. The remaining patients were alive at the last follow-up and were aged between 2 and 13 years. Patients suffered from infections including chronic mucocutaneous candidiasis (n = 10), salmonellosis (n = 2), and Leishmania (responsible for visceral form) (n = 2). Thirteen patients presented with autosomal recessive (AR) IL-12Rβ1 deficiency, meaning their cells produced low levels of IFN-γ. Bi-allelic IL12RB1 mutations were detected in nine of patients. Three patients with AR IL-12p40 deficiency (bi-allelic IL12B mutations) produced low levels of both IL-12 and IFN-γ. Overall, we found five mutations in the IL12RB1 gene and three mutations in the IL12B gene. Except one mutation in exon 5 (c.510C>A) of IL12B, all others were previously reported to be loss-of-function mutations., Conclusions: We found low levels of IFN-γ production and failure to respond to IL12 in 13 Iranian MSMD patients. Due to complicated clinical manifestations in affected children, early cellular and molecular diagnostics is crucial in susceptible patients.

Background: The actual prevalence of paediatric asthma as a worldwide chronic disease has been surveyed in developed countries. However, no sufficient survey has been conducted in most of the eastern developing countries. Herein, we took measures to evaluate the prevalence of paediatric asthma in Iran., Methods: In this national cross-sectional study, the prevalence of asthma symptoms was estimated throughout the country using a randomized multistage stratified cluster sampling method in 16 410 and 16 850 individuals aged 6-7 and 13-14 years, respectively. A validated questionnaire including core questions of the International Study of Asthma and Allergies in Childhood (ISAAC) was applied between November 2015 and February 2016., Results: The total prevalence of asthma was 10.9% (n = 3624) (95% confidence interval [CI]: 10.6%-11.2%) which was significantly higher among 13- to 14-year olds compared to a younger age group (12.4% vs. 9.4%, P < 0.001), males versus females (12.1% vs. 9.8%, P < 0.001) and residents of urban compared to rural areas (P = 0.003). The prevalence of severe asthma was 3.9%, being significantly more prevalent in higher age groups and male individuals (P < 0.001). A significant relationship was found between asthma and passive smoking in both 6- to 7- and 13- to 14-year olds (P < 0.001)., Conclusions: The prevalence of asthma and severe asthma in the paediatric population of Iran was similar to other developing countries. It is recommended to pay special attention to urban regions, male individuals and higher age groups for better controlling of asthma. Nevertheless, further national surveys are necessary to determine the trend of paediatric asthma in Iran., (© 2018 John Wiley & Sons Ltd.)

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., Competing Interests: Conflict of interest The authors declare that there is no conflict of interests.

T-cell receptor excision circles (TRECs) and κ-deleting recombination excision circles (KRECs) are recently used for detection of T or B cell lymphopenia in neonates based on region-specific cutoff levels. Here, we report cutoffs for TREC and KREC copies useful for newborn screening and/or diagnosis of primary immunodeficiency diseases (PID) in Iran. DNA was extracted from a single 3.2 mm punch of dried blood spots collected from 2160 anonymized newborns referred to two major referral health centres between 2014 and 2016. For refinement of the cutoffs, 51 patients with a definite diagnosis of severe combined immunodeficiency, X-linked agammaglobulinaemia and combined immunodeficiency, including ataxia telangiectasia, human phosphoglucomutase 3 and Janus kinase-3 deficiency, as well as 47 healthy controls were included. Samples from patients with an X-linked hyper-IgM-syndrome, Wiskott-Aldrich syndrome and DNA ligase 4 deficiency were considered as disease controls. Triplex-quantitative real-time PCR was used. Cutoffs were calculated as TRECs < 11 and KRECs < 6 copies with an ACTB > 700 copies with sensitivity of 100% for TREC and 97% for KREC. Among thirty anonymized newborn samples (1.5%) with abnormal results for TREC and/or KREC, only twenty-one available cases were retested and shown to be in the normal range except for three samples (0.15%). All of the patients with a definitive diagnosis were correctly identified based on our established TREC/KREC copy numbers. Determining cutoffs for TREC/KREC is essential for correctly identifying children with PID in newborn screening. Early diagnosis of PID patients enables appropriate measures and therapies like stem cell transplantation., (© 2018 The Foundation for the Scandinavian Journal of Immunology.)

Background and Objective: Asthma and chronic obstructive pulmonary disease (COPD) could be considered as a major health problem in industrialized and developing countries. This study was designed to analyze the trends of mortality from asthma and COPD at national and subnational levels in Iran based on National Death Registry, from 2001 to 2015., Materials and Methods: We used Death Registration System (DRS) as the basic source of data. Death Registration System data were available from 1995 to 2010 in Iran's Ministry of Health. Although, Tehran and Isfahan, 2 most populated cities in Iran, had independent death registry systems in their cemeteries, by combining their data we achieved more comprehensive and representative data on death among Iranian people. We addressed incompleteness and misclassification of death registry system using demographic and statistical methods. We also employed spatio-temporal and Gaussian process regression to extrapolate and interpolate mortality rates for the missing data., Results: Age-standardized asthma mortality rate was 7.2 (5.6-9.2) in females and 8.8 (6.9-11.1) in males at the national level in 2015. Age-standardized COPD mortality rates in females and males, respectively, were 8.46 (6.6-10.9) and 12.38 (9.8-15.6) during the studied years. A reduction in age-standardized asthma mortality was observed during the period of study. In addition, the trend of COPD mortality was increasing., Conclusions: It seems that mortality rate attributable to COPD has risen during the past 15 years in Iran. It could have increased because of increased exposure of people to related risk factors such as air pollution which is a common problem in larger cities and border provinces., (© 2018 John Wiley & Sons Ltd.)

Iron Deficiency Anemia (IDA) is a universal health problem and a risk factor for the development of cancer. IDA changes the microenvironment of the human body by affecting both the biological and immunological systems. It increases DNA damage and genomic instability by different mechanisms. IDA is one of the leading causes of the imbalance between different antioxidant enzymes as well as enzymes involved in DNA damage and DNA repair systems of the body. It can affect the biogenesis/expression of microRNAs. IDA interrupts the oxidative phosphorylation energy metabolism and intestinal Cytochrome-P450 systems. It also disturbs multicellular signaling pathways involved in cell survival and helps in tumor angiogenesis. Moreover, IDA is also responsible for the functional deterioration of innate and adaptive immune systems that lead to immunological dysfunctions against invading pathogens. Genomic instability and immunological dysfunctions are the hallmarks of cancer development. In this review, we will review the evidence linking IDA to increased cancer risk.

Background: The worldwide increase in the prevalence of asthma has made it a major public-health concern. We aimed to identify the prevalence of asthma and asthma symptoms in adults living in urban and rural areas of Iran as a populated country with about 80 millions of residents., Methods: This cross-sectional study was conducted to estimate the prevalence of asthma in adults between 20 and 44 years old in all provinces of Iran. Data were collected by personal interview via a standardized questionnaire [European Community Respiratory Health Survey (ECRHS)] between November 2015 and February 2016., Results: A total of 24 344 individuals were enrolled. The prevalence of asthma was 8.9% [95% confidence interval (CI): 8.5-9.3]. The most common asthma symptoms were wheezing (14.2%, n = 3465), nocturnal cough (13.3%, n = 3234) and chest tightness (11.3%, n = 2760). Additionally, the prevalence of current asthma (taking asthma medications or asthma attack) was estimated to be 4.7% (n = 1155). Asthma was significantly more prevalent in males compared to females (P = .002), while no significant relationship was detected between gender and asthma after adjusted analysis with other variables. The prevalence of asthma was significantly higher in older participants (P < .001) and individuals with low educational level (P < .001). Interestingly, there was no significant relationship between asthma and area of residency (P = .8)., Conclusions: The prevalence of asthma in Iran was similar to other Asian and European countries. However, repeated national surveys are required to determine the trend of asthma prevalence in Iran in comparison to other countries., (© 2017 John Wiley & Sons Ltd.)

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 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<0.001)., Conclusion: Regarding the presence of 20 allergens in a RIDA allergy panel and according to our findings, this immunoblotting test with high sensitivity could be used as a fast and cost-efficient screening test. However, ImmunoCAP is recommended when the accurate level of specific IgE is required. ImmunoCAP findings are particularly helpful for immunotherapy and the elimination diet., Competing Interests: Conflict of Interest: There is no conflict of interest to be declared.

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., Competing Interests: Conflict of Interests The authors declare that there is no conflict of interests.

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.

Introduction: Despite reports of response to steroid inhaler in some clinically suspected asthma patients with negative methacholine challenge test (CSA/MCT-), treatment in these patients has not been prospectively studied., Objective: We studied the role of a 12 week high dose inhaled fluticasone trial in CSA/MCT- patients., Methods: After a 2 week run-in period, CSA/MCT-patients were treated with 12 weeks of Fluticasone propionate 1000 µg/day. The Asthma Control Test (ACT), numeric cough score (NCS) and bronchodilator use were compared with their pretreatment values., Results: Thirty-four of 42 CSA/MCT-patients completed the study. Mean pretreatment ACT score (pACT) was significantly increased after treatment (14.7 ± 3.37 to 20.9 ± 3.1, P < 0.001). Posttreatment values of daytime (1.0 ± 1.0) and night-time (0.6 ± 0.9) NCS decreased compared to their pretreatment values (2.8 ± 1.1 and 1.9 ± 1.3, respectively; P < 0.001). ACT score change (ΔACT) were significantly greater in those with pACT < 15 than in those ≥15 (P < 0.001) . Fifteen of 21 patients with ΔACT > 5 did not need to use bronchodilator for their symptom relief. Wheeze disappeared in all six patients with ΔACT > 5 after the trial. Six months after the study, steroid inhaler continued to be used by 72.2% of patients., Conclusion: A significant portion of CSA/MCT- (especially those with pretreatment ACT score <15) respond to high dose fluticasone inhaler in terms of symptoms relief, disappearance of wheeze and need to bronchodilator use. ΔACT could not be predicted with any individual symptoms or signs before MCT, % FEV1 decline or symptoms during MCT and exhaled nitric oxide., (© 2015 John Wiley & Sons Ltd.)

Asthma is a complex, heterogeneous and chronic airway inflammatory disease with different clinical phenotypes caused by diverse triggers and pathophysiological mechanisms. Asthma heritability has been established in many genetic studies but it is evident that only genetic elements are not responsible for the development of asthma. Increasing rate of asthma incidence during past decades has implicated the role of epigenetics in development of asthma. Environmental factors perform as initiator signals through epigenetic mechanisms. Three epigenetic mechanisms have been identified, including DNA methylation, histone modifications, and small noncoding RNAs. These mechanisms regulate the immune responses and inflammatory genes expression in asthma and allergy. This review explains the role of epigenetic modifications in controlling Th2 response and IgE production in asthma and also briefly overviews the role of environmental factors such as pollutions, allergens, prenatal exposures and diet in developing asthma. Recognizing environmental risk factors and their effects on epigenetic mechanisms would be of great interest for prognostic and preventive aspect in treatment of asthma.

Background: To evaluate quality of life (QoL) and psychological score in adults with allergic rhinitis (AR) and to assess the possible risk factors., Materials and Methods: A total of 110 adult patients with a define diagnosis of AR, who were referred to an outpatient clinic of allergy and immunology, were included in this study. The modified Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was applied for the evaluation of QoL in these patients. The psychological score was also assessed, using the Esprint-15 questionnaire., Results: In a total of 110 patients (68 women, 42 men) with the mean±SEM age of 31.92±1.03 years, nasal congestion was the most common symptom (89.1%). Fifty-one (51%) out of 110 AR patients were found to have olfactory dysfunction (OD; hyposmia, 38%; anosmia, 13%). The relationship between nasal congestion and psychological score was significant (P= 0.005). OD had a significant relationship with QoL, as well as the psychological score (P= 0.001 and P= 0.003, respectively). Furthermore, psychological score had a significant relationship with reduction in QoL and sleep impairment (r, +0.654 and r, +0.591, respectively; P< 0.001). Statistical analysis showed that 54.5% of patients had a high psychological score, which was more common in females, although gender differences were not significant., Conclusion: Considering the increasing prevalence of AR and the significant relationship of OD and sleep impairment with QoL and psychological score, early diagnosis and treatment of AR may be important in improving QoL.

Background: Unconfirmed beta-lactam allergy is a significant public health problem because of the limitations it imposes in drug selection. In this study, we aimed to evaluate patients referred for beta-lactam allergy to determine the frequency of confirmed beta-lactam allergy and identify some risk factors., Methods: In a prospective cohort study, all referred patients to Immunology, Asthma and Allergy Research Institute in Tehran University of Medical Sciences (between 2007 - 2009) who suspected to have beta-lactam allergy were entered into this study based on having the inclusion criteria. Follow-up was performed 6 - 8 years after the final diagnosis. Diagnosis of beta-lactam allergy relies on thorough history and specific IgE measurements (ImmunoCAP), skin prick testing (SPT), intradermal testing (IDT), patch testing, and oral drug challenge test., Results: Fifty-one patients with mean age of 24.5 (±18.5) years were enrolled in this study. Based on workups, beta-lactam allergy was confirmed in 16 (31.4%) patients, suspicious in 22 (43.1%) patients and ruled out in 13 (25.5%) patients.  During the follow-up, 3 patients with suspicious drug allergy consumed the culprit drug with no reaction so allergy was finally ruled out in 16 (31.4%) patients. Age, sex, atopy and family history of drug allergies were not significantly different between the patients with confirmed or ruled-out diagnosis of penicillin and amoxicillin allergy., Conclusion: At least up to one-third of patients with a history of beta-lactam allergy are proven to be safe using the drug. Also, a clear protocol consists of serum sIgE assay and SPT can be helpful to the physicians in the health care system.

Asthma is a chronic respiratory disease characterized by airway inflammation, bronchoconstriction, airway hyperresponsiveness and recurring attacks of impaired breathing. Vasoactive intestinal peptide (VIP) has been proposed as a novel anti-asthma drug due to its effects on airway smooth muscle relaxation, bronchodilation and vasodilation along with its immunomodulatory and anti-inflammatory properties. In the current study, we investigated the therapeutic effects of VIP when conjugated with α-alumina nanoparticle (α-AN) to prevent enzymatic degradation of VIP in the respiratory tract. VIP was conjugated with α-AN. Balb/c mice were sensitized and challenges with ovalbumin (OVA) or PBS and were divided in four groups; VIP-treated, α-AN-treated, α-AN-VIP-treated and beclomethasone-treated as a positive control group. Specific and total IgE level, airway hyperresponsiveness (AHR), bronchial cytokine expression and lung histology were measured. α-AN-VIP significantly reduced the number of eosinophils (Eos), serum IgE level, Th2 cytokines and AHR. These effects of α-AN-VIP were more pronounced than that seen with beclomethasone or VIP alone (P<0.05). The current data indicate that α-AN-VIP can be considered as an effective nano-drug for the treatment of asthma., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In this study, we aimed to conduct a meta-analysis on the results of eligible studies to estimate the prevalence of asthma, COPD, and Chronic bronchitis in Iran. International and Iranian databases including PubMed, Scopus, Web of Science, Iranmedex, and scientific information database (SID) were searched for population-based studies that had reported the prevalence of asthma and COPD from 1990 to 2015. We conducted the meta-analysis using metaprop application of Stata statistical software. I-Squared was used for calculating heterogeneity among the studies. To determine causes of heterogeneity, subgroup analysis and meta-regression method were used. Based on the results of random effect method, the overall prevalence of asthma ever was 4.56% (3.76%-5.36%) among men while it was 4.17% (3.42%-4.91%) among women. Pooled prevalence of current asthma was 7.95% while confidence interval changed from 5.85% to 10.06% (men 5.83% (2.75%-8.92%), women 9.13% (3.35%-14.94%)). Also based on the results of random effect model pooled prevalence of chronic bronchitis of five studies was 5.57%. It seems that the total crude prevalence of current asthma in Iran is less than many other countries such as Kuwait, Lebanon, Thailand, Japan, Australia and Germany and is higher than some other countries such as Oman, Pakistan, South Korea, India, China, Taiwan, Indonesia, Spain, Russia, and Greece. On the other hand, Iran is in middle situation in terms of the prevalence current asthma. Our results can fill the information and knowledge gaps about the status of the prevalence of respiratory diseases in Iran.

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.

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.

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.

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.

Background: Asthma is a chronic inflammatory airway disease caused or worsened by environmental factors in genetically vulnerable people. The study of national and sub-national burden of asthma aims to provide a quantitative method and valid estimates for the prevalence, incidence, and economic burden of asthma disease in Iran from 1990 to 2013 and this papers explains measures, data sources, methods, and challenges that we will use in the study., Methods: In order to conduct this study, we will use all available unpublished data sources, including claim databases and data collected by the food and drug organization (FDO). Moreover, we will devise and run a systematic review of all studies and literature published about asthma epidemiology in Iran, which includes all cross-sectional, cohort and case-control studies with asthma epidemiology focus that are population based. In this study, we will use two statistical models, including spatio-temporal and multilevel autoregressive models to estimate mean and uncertainty intervals for the parameters under study by gender, age, year, and province. All programs will be written in R statistical packages (version 3.0.1)., Conclusion: This study helps to obtain information concerning the variation among regions and provinces, and in general among sub-national divisions. Our study can be contribute to better allocation of resources, since it helps policymakers to recognize inequalities between regions and provinces and consequently help them to allocate resources more efficiently.

Background: Serum inflammatory mediators and white blood cells (WBC) counts in the blood of sensitized and lead exposed guinea pigs were evaluated., Methods: Guinea pigs were randomly allocated into control (C), sensitized (S) and sensitized groups exposed to three lead concentrations (0.1, 0.2 and 0.4 M) during (DS) and after sensitization (PS), (n = 6 for each group). Animals were sensitized by intra-peritoneal injection and aerosol inhalation of ovalbumin (OA). Serum total protein, PLA2, IgE, histamine, total and differential WBC counts of blood were evaluated., Results: Serum PLA2, total protein, IgE, histamine, total and differential WBC counts in all three sensitized groups were significantly increased, but the percentage of lymphocyte was decreased compared to control group (p < 0.05 to p < 0.001). Serum total protein and total WBC number in all animals exposed to lead as well as the eosinophil and histamine in animals exposed to highest lead concentration and IgE in sensitized groups exposed to lead after sensitization were significantly higher, but the lymphocyte in animals exposed to two higher lead concentrations was lower than non exposed sensitized group (p < 0.05 to p < 0.001). The changes in all parameters in lead exposed animals after sensitization were higher than those during sensitization which was statistically significant for total WBC count in the animals exposed to low lead concentration (p < 0.05)., Conclusion: Inhaled lead can increase serum total protein, PLA2, IgE and histamine levels, total and most differential WBC counts in sensitized animal which was more pronounced in animals exposed to lead after compared to those during sensitization.