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Introduction: There has been substantial increase in food allergies in recent decades. The management of severe food allergy often includes strict avoidance and medical therapies. However, oral immunotherapy (OIT) is a promising treatment option for these patients, which is still being investigated. Methods: The study recruited children from 2 years onward with a history of wheat anaphylaxis who had been referred to the Mofid Children Hospital. Wheat allergy was confirmed by a double-blind placebo-controlled food challenge. OIT was started to reach 5.28 g of wheat protein supplied in 60 g of bread. Besides immunologic measurements, a second and third oral food challenge (OFC) was performed after 3 months and 1 year of maintenance therapy to evaluate the long-term efficacy of wheat OIT (WOIT). Results: Seventeen patients completed the 3-month maintenance phase; 8 of them demonstrated negative OFCs. All of the 9 with positive OFCs were asked to continue the daily consumption of 60 g of bread for another year. Three patients with positive OFCs were followed for 1 more year and were asked to continue eating 60 g of bread every other day. The serum level of wheat sIgE was significantly increased at the end of the buildup phase (p = 0.026) and dramatically dropped at the end of the maintenance phase (p = 0.022). Conclusion: To conclude, WOIT is an effective and safe modality of treatment if it is administered under strict supervision.

Background: There are three broad types of food allergies, including IgE-mediated reactions, non-IgE-mediated reactions, and mixed reactions. The onset of IgE-mediated food allergies is usually rapid and can sometimes lead to serious illness. Non-IgE-mediated and mixed types of food allergies can cause significant morbidity as a result of chronic disease. Objectives: This study aimed to compare various types of food allergies and discuss the basis of their different presentations. Methods: This study was conducted on children aged 2 - 12 years old with signs or symptoms of food allergy in the allergy clinics of Azad University Hospitals, Tehran, Iran, from January 2019 to January 2020. Food allergy was evaluated in these patients by careful history, physical exam, skin prick test, and atopy patch test. Results: A positive family history of atopy was detected in the first-degree relatives of 82 (63%) patients. All the children were exclusively breastfed at the beginning. A total of 61 patients had positive skin prick test (SPT), and 68 patients had positive atopy patch test (APT) results. Among food allergens, a significant correlation was detected between positive atopic patch test results and hypersensitivity reactions to cow’s milk (P value = 0.001), beef (0.002), and tomato (0.04). There was the same significant correlation between positive skin prick test results, allergens, and wheat (P value = 0.01). Conclusions: Although skin prick and atopy patch tests may help identify the culprit foods, oral food challenges are the mainstay of the diagnosis.

Background: Asthma is one of the most common chronic diseases triggered by viral respiratory infections leading to severe exacerbations. This study was performed to compare asthma with other underlying systemic disorders in coronavirus patients of 2019 (COVID-19) to evaluate any significant difference between these two groups in terms of ICU admission. Method: The study was a retrospective study using hospital records of patients’ from Intensive Care Units of Azad University hospitals in Tehran. Adult patients admitted to intensive care unit (ICU) due to COVID19 infection for a period of one year from March 2020 to February 2021, were enrolled in this cross-sectional study and their anonymized information was collected from an electronic system. Results: This study evaluated a total of 160 COVID-19 patients, aged 29 to 92 years old (mean age: 63.03±15.67 years). 90 (56.3%) patients were males and 70 (43.7%) were females. Comparing the mortality rate of COVID-19 patients with underlying systemic disorders to those with asthma showed that there was no significant difference between them. However, the rate of ICU admission in COVID-19 patients with diabetes and hypertension were significant compared with asthma (P =0.03). Conclusion: Asthma does not increase the risk of ICU admission in case of COVID-19 infection. Among the ICU admitted patients due to COVID-19 infection, the presence of asthma is not necessarily associated with a significant increase in poor outcomes.

BACKGROUND: The inborn errors of immunity (IEIs) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections besides other complications including autoimmune and inflammatory diseases. In this study, we aim to evaluate clinical, immunological, and molecular data of monogenic IEI patients with and without autoimmune manifestations. METHODS: We have retrospectively screened cases of monogenic IEI in the Iranian PID registry for the occurrence of autoimmunity and immune dysregulation. A questionnaire was filled for all qualified patients with monogenic defects to evaluate demographic, laboratory, clinical, and molecular data. RESULTS: A total of 461 monogenic IEI patients (290 male and 171 female) with a median (IQR) age of 11.0 (6.0-20.0) years were enrolled in this study. Overall, 331 patients (72.1) were born to consanguineous parents. At the time of the study, 330 individuals (75.7) were alive and 106 (24.3) were deceased. Autoimmunity was reported in 92 (20.0) patients with a median (IQR) age at autoimmune diagnosis of 4.0 (2.0-7.0) years. Sixteen patients (3.5) showed autoimmune complications (mostly autoimmune cytopenia) as the first presentation of the disease. Most of the patients with autoimmunity were diagnosed clinically with common variable immunodeficiency (42.4). The frequency of sinusitis and splenomegaly was significantly higher in patients with autoimmunity than patients without autoimmunity. In patients with autoimmunity, the most common pathogenic variants were identified in LRBA (in 21 patients, 23.0), ATM (in 13 patients, 14.0), and BTK (in 9 patients, 10.0) genes. In the evaluation of autoimmunity by different genes, 4 of 4 IL10RB (100), 3 of 3 AIRE (100), 21 of 30 LRBA (70.0) mutated genes had the highest prevalence of autoimmunity. CONCLUSIONS: Autoimmune phenomena are common features among patients with monogenic IEI and are associated with a more complicated course of the disease. Therefore, when encountering autoimmune disorders especially in the setting of dysgammaglobulinemia, it would be appropriate to conduct next generation sequencing (due to phenocopies of IEI genes) to discover responsible genes for the immune dysregulation at an early stage of the disease.

Background: IL-17 producing T cells are a distinct subset of CD4+ T cells, which are recognized to have an essential role in protection against certain fungi and extracellular pathogens. Objectives: This study aims to evaluate the number of IL-17 producing T cells as a predictor of primary immunodeficiency disorders in patients with Candida infections and low numbers of IL-17 producing T cells. Methods: Seven newly diagnosed patients with documented Candida infections aged between 4 and 35 years were included in this study. Before establishing the diagnosis of chronic mucocutaneous candidiasis, a thorough immunodeficiency workup, including complete blood count, serum Ig levels and antibody responses, flow-cytometry evaluation, and LTT, was completed for all the patients, and other immunodeficiency disorders, including combined and phagocytic deficiencies, were ruled out. Then, IL-17 producing T cells were detected using antiCD3 and anti-IL-17 antibodies through flow-cytometry evaluation. Results: The IL-17 producing T cells significantly decreased in the peripheral blood of patients with PID and candida infections. A P-value of less than 0.05 was considered statistically significant. Conclusions: To conclude, in cases of recurrent candida infections, initial assessment of IL-17 producing T cells may act as a predictor of an underlying primary immunodeficiency. In patients with low counts of IL-17 producing T cells, selecting a targeted panel of genetic tests may become more helpful in the detection of certain immunodeficiency disorders than performing whole-exome sequence analysis.

Background: Eosinophilic gastrointestinal disorders or diseases (EGIDs) may result from an abnormal immune-mediated response to food antigens. Activated eosinophils release various mediators with inflammatory properties which may result in tissue and subsequently organ damage. The cytokine milieu of these patients has revealed increased levels of pro-inflammatory cytokines, including interleukin (IL)-17. This study aims to evaluate the potential role of this cytokine in the pathogenesis of EGID.Materials and Methods: This prospective study was conducted at the Allergy Outpatient Clinic, Mofid Children Hospital, Tehran, Iran from January 2016 to January 2017. In this study, Serum IL-17 was determined in all the patients referred to the Allergy Clinic with a pathologic diagnosis of EGID. Results: The median (minimum and maximum) serum IL-17 level in patients with EGID, gastroesophageal reflux disorder (GERD), and healthy controls were 4.32 (0.00-6.383), 2.82 (0.00-3.231), and 3.6 (0.00-7.165) pg/mL, respectively. The results of the non-parametric analysis revealed no significant difference between the three groups regarding IL-17 (P=0.16). However, by classifying EGID in two separate groups with the involvement of upper (eosinophilic esophagitis and eosinophilic gastritis) and lower (eosinophilic enteritis, eosinophilic colitis) gastrointestinal (GI) tracts, a significant difference in serum IL-17 level became evident (P=0.004). Conclusion: We found a significant relationship between IL-17 and upper GI involvement in EGID.

Asthma and anaphylaxis are two atypical presentations of hyper‐IgE syndrome (HIES). Early diagnosis and management of HIES can improve quality of life of patients through minimizing orthodontic problems and other complications related to this disorder.

Introduction: Immunodeficient children are at a high risk of disseminated Bacillus Calmette-Guérin [BCG] infection. We assessed the literature on clinical manifestations of BCGosis in children with specific primary immunodeficiencies. Material and methods: We conducted a systematic review of clinical practice articles by searching Medline, PubMed, Embase, Scopus, Web of Science and Google Scholar from their inception to date. Results: Thirty-seven articles were included regarding BCG vaccination and its dissemination in children with primary immunodeficiencies. Articles on dissemination after intravesicular BCG were excluded from the study. Conclusions: Since disseminated BCG vaccination may be the first manifestation of a primary immunodeficiency disease, a comprehensive search for immunological defects in children developing these problems after BCG vaccination seems rational.

Leukocyte adhesion deficiency type-1 (LAD-1) is a rare primary immunodeficiency that is characterised by compromised neutrophil adhesion and transmigration to infection or inflammation sites. In this article, the authors report the cases of five patients with LAD-1 deficiency. The aim of this study is the demonstration of the wide variety of manifestations in these patients with a review of the literature. Patients were both male and female, with their ages ranging from 1 month to 10 years old. Omphalitis was the most common presentation in this series, followed by pneumonia and gingivitis. Impaired wound healing and cellulitis were other common findings in these patients. Two of the patients did not show delayed separation of the umbilical cord. The findings indicate that LAD-1 remains a life-threatening condition with omphalitis, oral, skin, respiratory tract, and ear infections as the most common complications. Early identification of these patients is essential in ensuring a definitive diagnosis and early implementation of haematopoietic stem cell transplantation.

Recent data has suggested a definitive role for inflammatory processes in the pathophysiology of epilepsy. In this study we hypothesized that food allergies, as chronic inflammatory processes, underlie the pathophysiology of refractory idiopathic epilepsy and investigated whether food elimination diets may assist in managing refractory epilepsy. The study was conducted on 34 patients up to 16 years of age with refractory convulsions who attended the Allergy Outpatient Clinic, Mofid Children Hospital between 2015 and 2016 with youngest and oldest participants at ages of 3 months and 16 years old, respectively. The participants were categorized into three groups according to the results of skin prick test and serum specific IgE measurements. Elimination diets were instituted for the patients with non IgE-mediated and mixed food allergies. The study was conducted for a period of 12 weeks. The participants were assessed for at least 50% reduction in number of seizures following the intervention. There was a significant reduction in number of seizures (p

Combined immune deficiencies (CIDs) are a heterogeneous group of inherited immune disorders characterized by impaired development, function, or both of T lymphocytes, with variable B cell defects. Among CIDs, a group of disorders is associated with syndromic features. The term CID syndromes apply to disorders in which other clinical features are present in addition to immunodeficiency. CID with associated or syndromic features comprises nine major categories including congenital thrombocytopenia, DNA repair defects, immunoosseous dysplasias (IODs), thymic defects with additional congenital anomalies, hyper-immunoglobulin E syndromes, dyskeratosis congenital, defects of vitamin B12 and folate metabolism, anhidrotic epidermodysplasia with ID and others. Most patients belonging to this group of primary immunodeficiency disorders manifest severe infections caused by opportunistic organisms, chronic diarrhea, failure to thrive, and recurrent and chronic respiratory infections. These patients present with less severe complications in the first year of life than severe CID patients, as evidence of immunodeficiency may be initially absent, whereas other clinical complications are present. Because syndromic CID can present initially with nonimmunologic manifestation, the various medical specialists involved in these cases should be aware of the signs and symptoms of this PID category.

Combined immunodeficiencies (CIDs) are the result of defective development or function of T cells. As the most severe form of primary immunodeficiency disorders (PID), CIDs are characterized by a susceptibility to infection, particularly from opportunistic organisms, which leads to severe morbidity and mortality. A subpopulation of patients has additional syndromic features caused by the function of the affected gene beyond the immune system. In this chapter, we will focus on nonsyndromic CIDs.

Food protein-induced enterocolitis syndrome (FPIES), is a non-IgE mediated food allergy presenting in infants younger than 12 months. Diagnostic delay may occur due to overlapping clinical symptoms with several conditions. Here, we present two cases of FPIES, mistakenly diagnosed and treated as Bartter syndrome. This study aims to emphasize the several features of this syndrome that may mimic other diagnoses and sometimes leading to near-death events due to delay in the diagnosis and improper treatment. The first patient was a 30-month-old boy with multiple episodes of profuse vomiting and diarrhea within 1 hour after breastfeeding, beginning from the first month of life progressing to hypokalemia and metabolic alkalosis at the age of 5 months leading to the diagnosis of Bartter syndrome. The second patient had a history of unremitting diarrhea which had been started soon after his first breastfeeding followed by biliary vomiting on the 7th day of life. He was treated in another hospital for neonatal sepsis, however, without an appropriate response to treatment. To conclude, despite the current belief on the rarity of FPIES, it is a more prevalent disease than expected with various non-specific manifestations imitating other conditions which may result in diagnostic delay and sometimes fatalities. To shed light on the importance of the physicians’ awareness of this syndrome, these two cases are presented here as examples of FPIES imitating other disorders.

Background: Food allergy which usually develops in the first year of life is a risk factor for persistent asthma in young children. Cow’s milk has been demonstrated to be the most commonly identified food allergen in children. Considering the central role of non-IgE-mediated food allergies in the development of hidden gastroesophageal reflux and consequently asthma, we evaluated the effect of eliminating food allergens to better control asthma. Method: A total of eighty infants and children up to the age of 12 referred to the Asthma Clinic of Mofid Children Hospital for a period of one year were enrolled in this study. In those patients whose asthma remained uncontrolled (Childhood Asthma Control Test ≤19) despite a 2-week period of treatment, we advocated a 2-week-diet based on eliminating cow’s milk in conjunction with asthma conventional therapy. For breast-fed infants, mothers were requested to eliminate these products from their daily intake regimens and for formula-fed infants, the elemental based formula was started. Results: Three of the patients were lost in follow-up and six of them were excluded from the study because of non-compliance. The Asthma Control Test score which was less than or equal to 19 in the entire study population, increased to 20 or more after we began a diet based on the elimination of cow’s milk in all but 13 participants. Conclusion: To conclude, the results were promising, demonstrating that a cow’s milk protein elimination diet is a prudent approach in the management of patients with recalcitrant asthma, and can be considered as the missing link in asthma treatment.

Asthma induced by ingestion of aspirin occurs when symptoms arise within 30 minutes to three hours after aspirin consumption. Previous data indicate that sensitivity to aspirin may be associated with poorly controlled asthma. This study aims to evaluate the frequency of aspirin sensitivity in patients with moderate to severe asthma receiving conventional asthma therapy. This clinical trial was conducted on 65 patients aged 18 to 65 years with moderate to severe asthma from February 2015 to February 2016 at the Allergy Department, Hazrat-e-Rasoul Hospital, Iran University of Medical Sciences, Tehran. To assess treatment responses in patients, forced expiratory volume in the first second (FEV1) and asthma control test (ACT) scores were measured at baseline and after 3 months. The results of the oral aspirin challenge revealed a prevalence of 35.38% for sensitivity to aspirin. Hypersensitivity reactions to aspirin were detected in 60.9% of the patients with moderate asthma and 39.1% of the patients with severe asthma. All patients with positive aspirin challenge tests suffered from rhinosinusitis and in 56.5% of cases, history of previous hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) was detected. No meaningful differences were found between those patients with aspirin sensitivity and those with aspirin tolerance neither in mean prebronchodilator FEV1 nor in ACT scores pre- and post-treatment. To conclude, aspirin sensitivity was not found to have an association with an unfavorable response to conventional treatment in patients with uncontrolled asthma.

Background: Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis. Methods: Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children’s Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data. Results: In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was LRBA, reported in 17 (63.0%) patients. Two patients (7.7%) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7%) developed one type of autoimmunity, and 16 patients (59.3%) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (n = 9, 90.0%) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (n = 6, 37.6%). In 13 patients (61.9%), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7%), gastrointestinal (48.1%), rheumatologic (25.9%), and dermatologic (22.2%) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity. Conclusion: In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity.

Background and aims Respiratory infections are expressed very soon in the life in humoral immunodeficiencies and often lead to chronic irreversible complications such as bronchiectasis and chronic airflow limitation. This study was conducted to evaluate the pulmonary complications of predominantly antibody immunodeficiencies to show the benefits of timely diagnosis and appropriate therapy. Patients and methods The information of 48 patients involved with a type of predominantly antibody immunodeficiencies, including sex, type of primary immunodeficiency, age at the onset of symptoms, age at diagnosis, recurrent infections, respiratory symptoms, and pulmonary radiological and functional abnormalities were recorded and analyzed. Results In 48 patients evaluated, the mean age at diagnosis was 25.63 years. The mean diagnostic delay was estimated to be 13.62 years. The most recurring clinical manifestations, sinusitis (69.6%), otitis (43.5%), and recurrent pneumonia were the cause of frequent admissions in 68.8% of these patients. Bronchiectasis was frequently found (58.3%) in these patients mostly involving the middle and lower lobes (48.8% and 41.5%, respectively). Conclusions Respiratory complications, infectious or non-infectious, determine the prognosis of the disease in patients with predominantly antibody immunodeficiencies. Timely diagnosis and appropriate management may improve life expectancy and the quality of life in these patients.

Background: The immunologic profile of chronic urticaria is not only important for diagnostic purposes, but also for therapeutic approaches. This study evaluated the serum levels of Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α) and Interferon-ϒ (IFN-ϒ) in patients with chronic urticaria to find a biomarker.Materials and Methods: Forty-one patients with chronic urticaria referring to the Allergy Outpatient Clinic of Rasoul Akram Hospital and 20 healthy control subjects were enrolled in the study. A questionnaire was filled and the disease activity score was determined in a one-week period for every patient. All patients underwent basic laboratory tests in addition to the Autologous Serum Skin Test. Their serum IL-6, TNF-α, and IFN-ϒ levels were also evaluated.Results: The patients were divided into two groups comprising of 20 and 21 participants according to the results of Autologous Serum Skin Tests. The serum IL-6 levels were elevated in the patients’ group (P=0.015). However, there was no significant difference between the patients with chronic urticaria and healthy controls in the serum levels of TNF-α (P=0.25), and IFN-ϒ (P=0.55), neither in the exact state nor by the Mann-Whitney U test.Conclusion: Serum IL-6 level was elevated in patients with chronic urticaria, but the serum levels of IFN-ϒ and TNF-α were not significantly elevated.

The number of inherited diseases and the spectrum of clinical manifestations of primary immunodeficiency disorders (PIDs) are ever-expanding. Molecular diagnosis using genomic approaches should be performed for all PID patients since it provides a resource to improve the management and to estimate the prognosis of patients with these rare immune disorders. The current update of Iranian PID registry (IPIDR) contains the clinical phenotype of newly registered patients during last 5 years (2013–2018) and the result of molecular diagnosis in patients enrolled for targeted and next-generation sequencing. Considering the newly diagnosed patients (n = 1395), the total number of registered PID patients reached 3056 (1852 male and 1204 female) from 31 medical centers. The predominantly antibody deficiency was the most common subcategory of PID (29.5%). The putative causative genetic defect was identified in 1014 patients (33.1%) and an autosomal recessive pattern was found in 79.3% of these patients. Among the genetically different categories of PID patients, the diagnostic rate was highest in defects in immune dysregulation and lowest in predominantly antibody deficiencies and mutations in the MEFV gene were the most frequent genetic disorder in our cohort. During a 20-year registration of Iranian PID patients, significant changes have been observed by increasing the awareness of the medical community, national PID network establishment, improving therapeutic facilities, and recently by inclusion of the molecular diagnosis. The current collective study of PID phenotypes and genotypes provides a major source for ethnic surveillance, newborn screening, and genetic consultation for prenatal and preimplantation genetic diagnosis.

Introduction Asthma exacerbations may occur due to a variety of triggers including respiratory viruses. The aim of this study was to determine the role of particular viral infections in asthma exacerbations in children. Materials and methods The study was performed at Dr. Daneshvari Hospital Pediatric Emergency Department, Shahid Beheshti University of Medical Sciences, Tehran, Iran between 2014 and 2015. A nasopharyngeal aspirate or swab was obtained from each patient during admission. All samples were maintained at 4 °C until submission to the virology laboratory and were tested for respiratory viruses by nucleic acid testing. Results A total of 60 patients with asthma exacerbations were recruited for this study. Of the 60 samples collected from the patients with acute asthma exacerbations, rhinovirus was detected in 12 patients (20%), respiratory syncytial virus in 5 (8%), adenovirus in 5 (8%), and influenza virus in 1 (1.6%). Respiratory pathogens were not detected in 37 (61%) samples. All the samples investigated showed single viral infection. Conclusions To conclude, the most common viruses detected were rhinovirus followed by respiratory syncytial virus (RSV) and adenovirus. RSV was more commonly associated with more severe attacks. Both the study design (e.g., time of sampling, age of the patients, etc.) and also the method used for viral detection influence the frequency of detection of the respiratory viruses.

Background: One of the most serious complications of BCG immunization is disseminated BCG infection, which is suggested to occur in immunized children with underlying primary immunodeficiencies. Objectives: This study aimed to assess the clinical manifestations and underlying primary immunodeficiencies associated with disseminated BCG infection. Methods: The study enrolled 47 patients suspected of disseminated BCG infection referring to Mofid Children Hospital and Masih Daneshvari Hospital for 12 years. The patients’ records were reviewed and patients were classified into three distinctive groups of definitive, probable, or possible disseminated BCG infection. Results: Twenty-five (53.2%) patients were male and twenty-two (46.8%) were female. The mean age at onset of clinical manifestations was 4.83 months. The first presentation of the disease occurred within one year of vaccination in 28 (60%) patients. Clinical manifestations included lymphadenopathies (61%), fever (38%), hepatosplenomegaly (36%), failure to thrive (23%), skin rash (14%), chronic cough (10%), ascites (6%), and clubbing (6%). The confirmed underlying primary immunodeficiency detected in these patients were Mendelian Susceptibility to Mycobacterial Disease (MSMD; 69.56%), Severe Combined Immunodeficiency (SCID; 26%) and Chronic Granulomatous Disease (CGD; 4.3%). Conclusions: Disseminated BCG infection may be a devastating complication and an important preliminary manifestation of underlying primary immunodeficiency. Because of the wide spectrum of mortality and morbidity, as well as the socioeconomic burden on the health system, it is worth to take a careful medical history before BCG immunization particularly in families with a history of consanguineous marriage and death due to unknown etiology.

Background Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiency disorders that is characterized by impaired early T lymphocyte differentiation and is variably associated with abnormal development of other lymphocyte lineages. SCID can be caused by mutations in more than 20 different genes. Molecular diagnosis in SCID patients contributes to genetic counseling, prenatal diagnosis, treatment modalities, and overall prognosis. In this cohort, the clinical, laboratory and genetic data related to Iranian SCID patients were comprehensively evaluated and efficiency of stepwise sequencing methods approach based on immunophenotype grouping was investigated Methods Clinical and laboratory data from 242 patients with SCID phenotype were evaluated. Molecular genetic analysis methods including Sanger sequencing, targeted gene panel and whole exome sequencing were performed on 62 patients. Results Mortality rate was 78.9% in the cohort with a median follow-up of four months. The majority of the patients had a phenotype of T-NK-B+ (34.3%) and the most severe clinical manifestation and highest mortality rate were observed in T-NK-B- SCID cases. Genetic mutations were confirmed in 50 patients (80.6%), of which defects in recombination-activating genes (RAG1 and RAG2) were found in 16 patients (32.0%). The lowest level of CD4+ and CD8+ cells were observed in patients with ADA deficiency (p = 0.026) and IL2RG deficiency (p = 0.019), respectively. Conclusion Current findings suggest that candidate gene approach based on patient's immunophenotype might accelerate molecular diagnosis of SCID patients. Candidate gene selection should be done according to the frequency of disease-causing genes in different populations. Targeted gene panel, WES and WGS methods can be used for the cases which are not diagnosed using this method.

Introduction: Wheat allergy can develop at any stage of life. The aim of this report was to demonstrate that skin testing and specific IgE have poor specificities and sensitivities for wheat allergy. Case Presentation: A 37-year-old female presented symptoms that were initiated immediately after consumption of bread and biscuits. She was well until two months prior to her recent admission. Her skin prick test, RIDA assay, and patch test for wheat showed negative results despite a history of two episodes of anaphylaxis. She underwent an oral food challenge, which confirmed wheat allergy. A desensitization procedure was recommended for her. At the end of the immunotherapy process, she had normal intake of wheat without any symptoms. Conclusions: Negative sIgE and SPT results do not rule out clinical food allergy. Oral food challenges are still the cornerstone of diagnosis of food allergy.

Background: Primary immunodeficiency disorders are a diverse group of rare genetic diseases that are often under-recognized. Therefore, significant morbidities and mortalities ensue due to diagnosis delay. This is an evaluation of clinical presentations and laboratory data of children referred to Mofid University Hospital during a 10-year period. The aim of this study is to provide epidemiologic data for early diagnosis and proper management of these patients. Methods: A total of 80 children referred to Mofid’s Children Hospital suspected to primary immunodeficiencies (PIDs) were evaluated clinically. The demographic, clinical, and laboratory data were collected in detail and were analyzed as a cross-sectional study. Missing data were completed in follow-up visits. Results: The prevalence of antibody deficiencies, phagocytic defects, and combined immunodeficiencies in 80 children with primary immunodeficiency syndromes were respectively 36.25%, 32.5%, and 31.25%. Common variable immunodeficiency (13.75%) and severe combined immunodeficiency (12.5%) had the highest prevalence among these disorders and the lowest prevalence were reported for cyclic neutropenia (5%), ataxia-telangiectasia (5%), and transient hypogammaglobulinemia of infancy (3.75%). The most common mode of inheritance detected was an autosomal recessive pattern. Pneumonia, otitis media, and diarrhea were the most common complications in the course of these disorders, which were seen respectively in 30%, 18.8%, and 15% of the patients. Conclusions: Issues regarding clinical presentation and management of primary immunodeficiencies continue to puzzle the clinical practitioner. Epidemiological data are needed to increase the awareness of the physicians regarding primary immunodeficiency disorders and to support the benefits of early diagnosis and treatment. Diagnosis delay is associated with increased morbidities and even mortalities.

BACKGROUND: Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses. OBJECTIVE: We intended to report most common monogenic PADs and to investigate how patients with PAD who were primarily diagnosed as suffering from agammaglobulinemia, hyper-IgM (HIgM) syndrome, and common variable immunodeficiency (CVID) have different clinical and immunological findings. METHODS: Stepwise next-generation sequencing and Sanger sequencing were performed for confirmation of the mutations in the patients clinically diagnosed as suffering from agammaglobulinemia, HIgM syndrome, and CVID. RESULTS: Among 550 registered patients, the predominant genetic defects associated with agammaglobulinemia (48 Bruton's tyrosine kinase BTK and 6 mu heavy chain deficiencies), HIgM syndrome (21 CD40 ligand and 7 activation-induced cytidine deaminase deficiencies), and CVID (17 lipopolysaccharides-responsive beige-like anchor deficiency and 12 atypical Immunodeficiency, Centromeric instability, and Facial dysmorphism syndromes) were identified. Clinical disease severity was significantly higher in patients with mu heavy chain and CD40 ligand mutations compared with patients with BTK (P = .003) and activation-induced cytidine deaminase (P = .009) mutations. Paralysis following live polio vaccination was considerably higher in patients with mu heavy chain deficiency compared with BTK deficiency (P < .001). We found a genotype-phenotype correlation among patients with BTK mutations regarding clinical manifestation of meningitis and chronic diarrhea. Surprisingly, we noticed that first presentations in most patients with Immunodeficiency, Centromeric instability, and Facial dysmorphism were respiratory complications (P = .008), whereas first presentations in patients with lipopolysaccharides-responsive beige-like anchor deficiency were nonrespiratory complications (P = .008). CONCLUSIONS: This study highlights similarities and differences in the clinical and genetic spectrum of the most common PAD-associated gene defects. This comprehensive comparison will facilitate clinical decision making, and improve prognosis and targeted treatment.

Background: Primary immunodeficiency disorders comprise a heterogeneous group of diseases in which there is a defect in the development or function of the immune system. Clinical presentation of these disorders is highly variable. The aim of this study was to determine the frequency and type of primary immunodeficiency disorders, diagnostic delay, common pathogenic microorganisms, and infectious complications in patients, admitted to Mofid Children’s hospital in the past decade (2004 - 2014). Methods: The data of patients with a diagnosis of primary immunodeficiency disorder, admitted to Mofid Children’s hospital from 2004 to 2014, were reviewed. The frequency, diagnostic delay, pathogenic microorganisms, and their sequelae were determined. Results: In 32 patients (20 males and 12 females) admitted to Mofid hospital in the past decade, chronic granulomatous disease was the most frequent primary immunodeficiency disorder (22%). Other immunodeficiency disorders in these patients included X-linked agammaglobulinemia, hyper IgM syndrome, common variable immunodeficiency, severe combined immunodeficiency, ataxia-telangiectasia syndrome, transient hypogammaglobulinemia of infancy, leukocyte adhesion deficiency, and Kostmann syndrome. The mean age at onset of these disorders was 15 months, and the mean delay in diagnosis was 20 months. Pneumonia was the most common infectious manifestation (53%), and Acinetobacter was the most common isolated microorganism. Conclusions: Diagnostic delay is a major concern in patients with primary immunodeficiency disorders. Ethnic and geographical differences may significantly influence the frequency and presentation of these disorders. Therefore, local epidemiological data are always necessary and useful in the management of primary immunodeficiency disorders.

Background Leptin is a pro-inflammatory cytokine produced by adipose tissue. Considering the association between obesity and asthma, the current study aimed at investigating if leptin was in the pathway of obesity-asthma relationship in children and if it played a distinctive role in children with asthma and obesity versus the ones with obesity but without asthma. Methods The current case-control study was conducted on 23 children with asthma and obesity and 13 children with obesity but without asthma (body mass index ≥ 95%) aged 6 to 15 years from October 2011 to October 2012 in Mofid Children’s Hospital, Tehran, Iran. Group 1 included 23 children with asthma and obesity with a mean BMI of 24.3 kg/m2, while group 2, included 13 cases with obesity but without asthma and a mean BMI of 26.6 kg/m2. Both groups were evaluated for their serum leptin, triglyceride, cholesterol, and IgE mean levels. The serum leptin levels were measured by the enzyme-linked immunosorbent assay (ELISA) technique. The results were analyzed with SPSS version 19. The Mann-Whitney test was employed to compare the results. Results The mean serum leptin level in the children with asthma and obesity was 2.19 ng/mL and in the ones with obesity but without asthma was 2.85 ng/mL (P = 0.006). The mean serum triglyceride and cholesterol levels in the group 1 were 175.4 mg/dL and 189 mg/dL, respectively, while in the group 2 were 175.4 mg/dL and 226.2 mg/dL, respectively. A significant difference was observed in serum leptin levels between the children in groups 1 and 2 (P = 0.006), but surprisingly the increased leptin was detected in the group 2 subjects. Conclusions The current study findings indicated that serum levels of leptin were significantly higher in the cases with obesity but without asthma. Therefore, other cytokines appeared to play a role in the children with asthma and obesity.

Background: Aeroallergens and food allergens are found to be relevant in atopic dermatitis. The atopy patch test (APT) can help to detect food allergies in children with atopic dermatitis. This study evaluates if the APT is a valuable tool in the diagnostic workup of children with food allergy-related atopic dermatitis. Methods: 42 children between 6 months and 12 years of age were selected at the Mofid Children Hospital. Atopic dermatitis was diagnosed, and the severity of the disease was determined. At the test visit, the patients underwent a skin prick test (SPT), APT, and serum IgE level measurement for cow's milk, egg yolk, egg white, wheat, and soy. Results: We found a sensitivity of 91.7%, a specificity of 72.7%, a positive predictive value (PPV) of 88%, a negative predictive value (NPV) of 80%, and an accuracy of 85.7% for APT performed for cow's milk. APT performed for egg yolk had a sensitivity and a NPV of 100%, while the same parameters obtained with egg white were 84.2 and 75%, respectively. The sensitivity, specificity, and NPV of the APT for wheat were 100, 75, and 100%, respectively. The sensitivity, PPV, and NPV of the APT for soy were 87.5, 70, and 87.5%, respectively. Conclusions: Our data demonstrate that the APT is a reliable diagnostic tool to evaluate suspected food allergy-related skin symptoms in childhood and infancy.

Hassanzad M, Farnia P, Darougar S, Velayati AA. A novel evaluation of genetic polymorphism in BCG adenitis. Turk J Pediatr 2019; 61: 466-470. Bacillus Calmette-Guerin (BCG) is a live attenuated vaccine which has been used to prevent tuberculosis, according to the World Health Organization (WHO) recommendation in parts of the world with an incidence of tuberculosis infection more than 1%. The incidence of BCG adverse reactions differs between regions with regional lymphadenitis as the most common presentation. The aim of this study was to detect the impact of polymorphisms causing BCG lymphadenitis in children receiving BCG vaccination at birth. Eight healthy infants with BCG adenitis from 4 to 12 months old were enrolled. All these patients underwent a thorough physical examination, abdominopelvic ultrasound evaluation to detect distant lymphadenopathies and immunodeficiency screening tests for any possible underlying immunodeficiency disorders. Then genotyping for known mutations was performed using restriction fragments length polymorphism (PCR-RFLP) assays. Sequencing was performed for IL-12 Rβ1, IFN-ϒ receptor 1, IL-10, TNF-α and P2X7. The mean age of onset of the adenitis was 6.5 months. TNF-857, IL-12Rβ1 705, IL-10 1082, and IFN-ϒ- 56 single nucleotide polymorphisms (SNPs) were common in the children studied. The most frequent polymorphism found in the patients with BCG adenitis except one, was the P2X7 -762 polymorphism. To conclude, these polymorphisms are more common in some ethnic populations but not others and make the genetic basis of immunity to BCG strains and the occurrence of post-BCG lymphadenitis in otherwise healthy children.

We report a 9-year old girl with an unusual presentation of granulomatosis with polyangiitis in association with Marfan phenotype. The patient presented with recurrent sinusitis, epistaxis, hearing loss and hyperplastic gingivitis, without any signs or symptoms of major organ involvement.

Introduction: Cystic fibrosis is a chronic disease with multiple organ involvement and chiefly results in chronic respiratory infections, pancreatic insufficiency and associated complications. The age at diagnosis, clinical presentation, rate of disease progression and prognosis is variable among patients. This study is designed to evaluate the behavior of disease to provide epidemiologic data for early recognition and proper management. Material and methods: The study was designed as an active surveillance of 192 patients diagnosed with cystic fibrosis in a tertiary lung disease centre between 2008 and 2015. The diagnosis of cystic fibrosis was established in all patients accordingly to conventional criteria, including two positive sweat chloride tests and clinical signs and symptoms. Demographic, clinical and laboratory data were obtained from these patients in each hospitalization and also every follow-up visit and carefully evaluated for complications of this chronic disease. Results: The majority of patients showed positive culture for Pseudomonas aeroginosa. Bronchiectasis was the most prevalent finding in chest CT scan. 44.3% of patients had been treated for allergic bronchopulmonary aspergillosis and all had sinus disease. Increased pulmonary artery pressure was observed in 40% of patients with cystic fibrosis. 33 patients died which consisted 17.1% of all the patients.The mean age of mortaliy was 18.15 year. Conclusions: The clinical outcome of cystic fibrosis is variable in different countries which may reflect environmental influences and the role of early diagnosis on long term outcomes. However, the role of early diagnosis in long-term outcomes of the disease can not be ignored.

Chronic granulomatous disease is a rare primary immunodeficiency disorder, which leads to increased susceptibility to recurrent infections and severe inflammatory manifestations. There have been reports regarding different aspects of genitourinary involvement in chronic granulomatous disease, some of which are hydronephrosis, granulomatous cystitis, and glomerulonephritis, but among these complications, amyloidosis is rather rare. We report a patient with chronic granulomatous disease that developed amyloidosis later in the course of the disease.

Wstęp: Mukowiscydoza jest wielonarządową chorobą przewlekłą, której głównymi następstwami są infekcje układu oddechowego, niewydolność trzustki i inne pokrewne powikłania. Wiek w czasie rozpoznania, przebieg kliniczny, tempo progresji i rokowanie są różne u różnych chorych. Celem prezentowanego badania była ocena przebiegu choroby i wpływu uwarunkowań epidemiologicznych na wczesne rozpoznanie i właściwe leczenie. Materiał i metody: Przeprowadzono aktywną ocenę prospektywną 192 chorych na mukowiscydozę, leczonych w ośrodku referencyjnym w latach 2008–2015. U wszystkich chorych rozpoznanie mukowiscydozy postawiono na podstawie obowiązujących kryteriów, w tym stwierdzenia dwóch dodatnich wyników potowego testu chlorkowego oraz obecności typowych objawów klinicznych. Dane demograficzne, kliniczne i laboratoryjne uzyskiwano od pacjentów podczas kolejnych hospitalizacji i wizyt kontrolnych. Dane te były szczegółowo oceniane pod kątem powikłań choroby podstawowej. Wyniki: U większości chorych stwierdzono dodatni wynik hodowli plwociny w kierunku Pseudomonas aeroginosa. Rozstrzenia oskrzeli były najczęściej występującym objawem w badaniu tomograficznym klatki piersiowej. W badanej grupie 44.3% chorych było leczonych z powodu alergicznej aspergilozy oskrzelowo-płucnej a u wszystkich chorych stwierdzono chorobę zatok przynosowych. Podwyższone ciśnienie w tętnicy płucnej stwierdzono u 40% chorych na mukowiscydozę. Zmarło 33 chorych, co stanowi 17.1% badanej grupy. Średni czas przeżycia wynosił 18.15 roku. Wnioski: Wyniki leczenia chorych na mukowiscydozę są różne w różnych krajach, co może odzwierciedlać wpływy środowiska, a także znaczenie wczesnego rozpoznania dla odległego rokowania. Znaczenie wczesnego rozpoznania dla odległych wyników leczenia nie powinno być lekceważone.

IL-17 is a major cytokine player in T cell mediated leukocyte associated inflammation. IL-17 is also recognized to participate in the pathophysiology of asthma.To determine the role of IL-17 in predicting severe asthma.We obtained serum samples from asthmatic children under the age of 5-year in three different groups of mild (n=33), moderate (n=28) and severe (n=32) persistent asthma. IL-17 serum concentrations and mRNA expression were determined by ELISA and real time PCR assays, respectively.Serum IL-17 concentrations were significantly higher in patients with severe asthma than the other two groups of children with mild and moderate disease (p=0.00). Mean serum IL-17 values were 142.04 pg/ml in mild group, 180.4 pg/ml in moderate group and 251.25 pg/ml in severe group. IL-17 mRNA levels were also significantly elevated in severe asthmatic patients compared to mild and moderate asthmatic children (p=0.00).Our data reveal an increase in the serum IL-17 concentration and IL-17 mRNA expression in children with severe asthma compared to those with mild and moderate forms of the disease.