Clinical and Mutation Description of the First Iranian Cohort of Infantile Inflammatory Bowel Disease: The Iranian Primary Immunodeficiency Registry (IPIDR).

We describe a cohort of 25 Iranian patients with infantile inflammatory bowel disease (IBD), 14 (56%) of whom had monogenic defects. After proper screening, patients were referred for whole exome sequencing (WES). Four patients had missense mutations in the IL10 RA, and one had a large deletion in the IL10 RB. Four patients had mutations in genes implicated in host:microbiome homeostasis, including TTC7A deficiency, and two patients with novel mutations in the TTC37 and NOX1. We found a novel homozygous mutation in the SRP54 in a deceased patient and the heterozygous variant in his sibling with a milder phenotype. Three patients had combined immunodeficiency: one with ZAP-70 deficiency (T+B+NK-), and two with atypical SCID due to mutations in RAG1 and LIG4. One patient had a G6PC3 mutation without neutropenia. Eleven of the 14 patients with monogenic defects were results of consanguinity and only 4 of them were alive to this date.

Bronchoalveolar galactomannan in invasive pulmonary aspergillosis: a prospective study in pediatric patients.

BACKGROUND: Elevations in the number of immunocompromised patients in the past decade has lead to progressive increase in the incidence of Invasive Pulmonary Aspergillosis (IPA) among children; however, early diagnosis remains a challenge. Detection of galactomannan (GM) in the bronchoalveolar lavage (BAL) fluid appears to possess higher sensitivity and specificity than serum in immunocompromised adult patients but, it rarely has been investigated in pediatric patients. METHODS: We performed a prospective case-control study to evaluate the efficacy of BAL GM in immunocompromised pediatric patients. Cases were subjects fulfilling the host factor criteria as defined by the EORTC/MSG and met established definitions for proven or probable IPA. Control group was patients with possible IPA in whom diagnoses other than IPA were confirmed and patients without risk factors of IPA who underwent bronchoscopy for other diagnostic purpose. Galactomannan testing was performed on BAL fluid samples using platelia Aspergillus seroassay. RESULTS: Sixteen cases of IPA (4 proven, 12 probable) and 54 controls (6 possible IPA and 48 no IPA) were documented according to EORTC/MSG definitions. The sensitivity and positive predictive values of BAL GM using an OD index of ≥0.5 were 87.5% and 93.33% respectively. We found seven cases of IPA with negative serum GM while their BAL GM was positive. CONCLUSION: We found high diagnostic value of BAL GM in immunocompromised pediatric patients with IPA. The lower OD index is necessary in children to avoid missing the cases of IPA in children.

Primary immunodeficiency disorders in Iran: update and new insights from the third report of the national registry.

BACKGROUND: Primary immunodeficiency disorders (PID) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections and increased susceptibility to malignancies, lymphoproliferative and autoimmune conditions. National registries of PID disorders provide epidemiological data and increase the awareness of medical personnel as well as health care providers. METHODS: This study presents the demographic data and clinical manifestations of Iranian PID patients who were diagnosed from March 2006 till the March of 2013 and were registered in Iranian PID Registry (IPIDR) after its second report of 2006. RESULTS: A total number of 731 new PID patients (455 male and 276 female) from 14 medical centers were enrolled in the current study. Predominantly antibody deficiencies were the most common subcategory of PID (32.3 %) and were followed by combined immunodeficiencies (22.3 %), congenital defects of phagocyte number, function, or both (17.4 %), well-defined syndromes with immunodeficiency (17.2 %), autoinflammatory disorders (5.2 %), diseases of immune dysregulation (2.6 %), defects in innate immunity (1.6 %), and complement deficiencies (1.4 %). Severe combined immunodeficiency was the most common disorder (21.1 %). Other prevalent disorders were common variable immunodeficiency (14.9 %), hyper IgE syndrome (7.7 %), and selective IgA deficiency (7.5 %). CONCLUSIONS: Registration of Iranian PID patients increased the awareness of medical community of Iran and developed diagnostic and therapeutic techniques across more parts of the country. Further efforts must be taken by increasing the coverage of IPIDR via electronically registration and gradual referral system in order to provide better estimation of PID in Iran and reduce the number of undiagnosed cases.

Skin Prick Test Reactivity to Common Aero and Food Allergens among Children with Allergy.

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

Inflammatory Markers in the Serum and Bronchoalveolar Lavage in Children with Non-Cystic Fibrosis Bronchiectasis.

Background: It is known that inflammatory responses occur in the airways of patients with non-cystic fibrosis bronchiectasis during respiratory exacerbations but the role of these cytokines is not clear in this condition. Herein we evaluated the levels of interleukin-1ß (IL-1ß), IL-8 and tumor necrosis factor α (TNF-α) in the serum and bronchoalveolar lavage among children with non-cystic fibrosis bronchiectasis. Materials and Methods: This cross-sectional study was performed on all children with non-cystic fibrosis bronchiectasis who were admitted with respiratory exacerbation in the pediatric pulmonology ward of Masih Daneshvari Hospital, Tehran-Iran. All patients underwent fiberoptic bronchoscopy and spirometry before and after the bronchoscopy. IL-1ß, IL-8, and TNF-α levels were measured in the serum and bronchoalveolar lavage. Results: Patients included 10 (59%) female and 7 (41%) male subjects with mean age of 13.8 years (range, 5-18). Mean values for forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were below the normal range before and after bronchoscopy. Mean value for FVC (from 55% to 63%, P= 0.01) and FEV1 (from 60% to 64%, P= 0.26) increased after bronchoscopy compared to before that. IL-1ß and IL-8 levels were increased and TNF-α level was decreased in the serum and bronchoalveolar lavage but no significant correlation was found between spirometry and these cytokines levels. Conclusion: Changes in inflammatory cytokines levels in serum and bronchoalveolar lavage during respiratory exacerbation in patients with noncystic fibrosis bronchiectasis have no significant correlation with spirometry and cannot be used in clinical practice.

Chest CT Manifestations in Children with CVID: A 10-Year Report.

BACKGROUND: This study aimed at evaluating HRCT pulmonary manifestations in children with Common Variable Immunodeficiency (CVID) hospitalized in the Pediatric Ward of Masih Daneshvari Hospital during a 10-year period. MATERIALS AND METHODS: This retrospective study evaluated 25 children hospitalized with the diagnosis of CVID in the Pediatric Ward of Masih Daneshvari Hospital from 2001 to 2011 and their pulmonary HRCT scans were evaluated. RESULTS: The most common pulmonary HRCT findings were lymphadenopathy (66.7%), bronchiectasis (50%), air trapping (33.3%) and peribronchial wall thickening (33.3%). The highest percentage of CT-scan findings was detected in patients aged 13-17 yrs. CONCLUSION: Most of the pulmonary changes due to CVID are preventable or treatable. Also, it is possible to prevent irreversible complications of disease if it is diagnosed early. Therefore, HRCT is strongly recommended as an accurate and effective method for monitoring and fast recognition of pulmonary manifestations of the disease especially bronchiectasis which is a very common finding indicative of poor prognosis.

IL-12Rß1 deficiency in two of fifty children with severe tuberculosis from Iran, Morocco, and Turkey.

BACKGROUND AND OBJECTIVES: In the last decade, autosomal recessive IL-12Rß1 deficiency has been diagnosed in four children with severe tuberculosis from three unrelated families from Morocco, Spain, and Turkey, providing proof-of-principle that tuberculosis in otherwise healthy children may result from single-gene inborn errors of immunity. We aimed to estimate the fraction of children developing severe tuberculosis due to IL-12Rß1 deficiency in areas endemic for tuberculosis and where parental consanguinity is common. METHODS AND PRINCIPAL FINDINGS: We searched for IL12RB1 mutations in a series of 50 children from Iran, Morocco, and Turkey. All children had established severe pulmonary and/or disseminated tuberculosis requiring hospitalization and were otherwise normally resistant to weakly virulent BCG vaccines and environmental mycobacteria. In one child from Iran and another from Morocco, homozygosity for loss-of-function IL12RB1 alleles was documented, resulting in complete IL-12Rß1 deficiency. Despite the small sample studied, our findings suggest that IL-12Rß1 deficiency is not a very rare cause of pediatric tuberculosis in these countries, where it should be considered in selected children with severe disease. SIGNIFICANCE: This finding may have important medical implications, as recombinant IFN-γ is an effective treatment for mycobacterial infections in IL-12Rß1-deficient patients. It also provides additional support for the view that severe tuberculosis in childhood may result from a collection of single-gene inborn errors of immunity.