Newborn screening using TREC/KREC assay for severe T and B cell lymphopenia in Iran.

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 centers 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. This article is protected by copyright. All rights reserved.

Mannan-binding lectin serum levels in 593 healthy Iranian children and adults.

Mannan-binding lectin (MBL) is a vital protein of innate immune system and has two critical functions: complement activation through the lectin pathway and opsonization. MBL deficiency has been classified as the most common inherited immunodeficiency known in humans (about 30% of the population), and is associated with predisposition to infections and high risk of some autoimmune diseases. The purpose of this study was to determine the profile of MBL serum level in Iranian healthy population in association with sex and age groups for the first time. We studied the serum concentration of MBL in 593 Iranian healthy cases: 340 males and 235 females in 4 different age groups by using enzyme-linked immunosorbent assay. The mean serum levels of MBL were 3.854 ± 2.77 µg/ml at the age of less than 6 months, 4.147 ± 3.54 µg/ml at 6 months to 2 years of age, 4.410 ± 3.09 µg/ml at 2-6 years and 2.207 ± 1.73 µg/ml in adults. There was significant differences in the mean concentration of MBL among different age groups of children and also between children and adults (p<0.05). No association was observed between sex and MBL concentrations. MBL serum levels of Iranian population seem to be different from some of other populations which may be explained by genetic variations. The MBL values in this study can be used as a normal reference range for future studies in Iranian population.

Common causes of anaphylaxis in children: the first report of anaphylaxis registry in iran.

BACKGROUND: : Anaphylaxis is an acute, systemic, and potentially fatal allergic reaction. Many things can cause anaphylaxis potentially but some agents are more common like some foods (milk, egg, soy, wheat, peanut, tree nut, shellfish, and fish), insect stings, medications, latex, and food-dependent exercise-induced anaphylaxis. The goal of this study is to show the common causes of anaphylaxis among the children with anaphylaxis history who were referred to the Immunology, Asthma and Allergy Research Institute (IAARI) during a 4-year period (2005-2009). METHODS AND MATERIALS: : During those 4 years, we registered all children (<14 years old) with a history of anaphylactic reaction. To prove the cause of anaphylaxis, we performed skin prick tests with suspected agents according to their history and measured specific IgE against them by the ImmunoCAP test. Recognition of common allergens was based on having a positive history for 1 allergen and positive skin prick test or specific IgE for that at the same time, or having positive results from both tests when the allergen was unclear. Idiopathic anaphylaxis was a reaction when any known allergen and positive tests were not obtained. RESULTS: : One hundred ninety-three nonfatal anaphylactic attacks among 63 children were recognized. In total, the most current cause of anaphylaxis in children was food (89.7%). Milk (49.3%) and wheat (26.1%) were the most common. Other foods were egg (8.7%), nuts (2.8%), and spices (2.8%). Six children (8.7%) were sensitive to multiple food allergens like milk, egg, and wheat. Five (7.1%) of 63 patients had anaphylactic attack because of stinging. Wasp was the trigger in 3 (4.3%) of them and honeybee was the cause in 1 (1.4%). The last one was because of unknown hymenoptera. There were 2 idiopathic cases of all 63 patients. CONCLUSIONS: : Food allergens, especially milk and wheat, are the most common cause of anaphylaxis in children. Because anaphylaxis can be fatal, it is advisable to recognize its causes in different communities to prevent recurrent attacks.

Clinical and laboratory findings in Iranian patients with leukocyte adhesion deficiency (study of 15 cases).

Leukocyte adhesion deficiency type I (LAD I) is a rare, inherited, autosomal recessive, immunodeficiency disease caused by the combined loss of expression on the surface of leukocytes of the leukocyte integrins. We describe the clinical and laboratory findings for 15 patients with LAD I. The range of patients' ages was from 10 month to 14 years (median 4 years) and 93.3% of their parents had consanguineous marriages. The most commonly occurred manifestations were: recurrent infections (93.3%), poor wound healing (86%), oral ulcers (86%), and skin abscesses (80%). The most specific laboratory findings were defect in CD18 in all of 15 patients. The most common symptoms in these patients are poor wound healing and oral ulcer, so, the clinical physicians should pay special attention to these symptoms. Furthermore, because of considerable rate of consanguineous marriages in parents of LAD patients, we suggested more genetic studies on this disease and genetic consultation for these families.