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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.

Objectives: This study aims to investigate niacin sensitivity in schizophrenia patients compared to healthy people and examine the accuracy of niacin skin flush test in diagnosing schizophrenia. Methods: This diagnostic study was conducted in 2018 in Zanjan, Iran. Three niacin concentrations (0.001 M, 0.01 M, and 0.1 M) was first applied topically to the skin of 36 schizophrenia patients and 33 healthy controls. Flush responses were evaluated at 10 and 15 min after application. Sensitivity, specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) of the test were measured for each niacin concentration and evaluation time. Results: At 10 min, the highest test accuracy was reported when 0.001 M niacin solution was used (Sensitivity=94%, specificity=50%, PPV= 51%, and NPV= 94%). At 15 min, the highest test accuracy was observed at 0.01 concentration (Sensitivity=52%, specificity=92%, PPV=79%, and NPV=77%). Conclusion: Flush responses to niacin is more impaired in patients with schizophrenia. Therefore, niacin can be considered as a biological marker of schizophrenia and can be used for its diagnosis.

Introduction: Researchers have been investigating the major pathogens involved in septic shock caused by lipopolysaccharide in recent years. Moreover, they have been concerned about the use of appropriate drugs to intervene with the main pathogenesis of the disease. This study aimed to investigate the effect of L-Glutamine as an HSP70 inducer in reducing pre-inflammatory cytokines and effective intermediaries in septic shock, including nitric oxide production and CD40 expression in mice treated with lipopolysaccharide (LPS). Materials & Methods: In total, 25 Swiss Albino mice were randomly divided into three groups of A (control group, n=5), (received LPS with a dose of 0.75 mg/animal intraperitoneally [IP], (n=10), and (received L-glutamine with a dose of 50 mg/kg IP 30 minutes after the injection of LPS [three doses every 24 h], (n=10). Subsequently, one day after the final dose of drug induction, the number of cytokines, such as IFN-γ, IL-4, IL-10, HSP70, CD40, and nitric oxide, were evaluated in this study. Ethics code: IR.TABRIZU.REC.1398.003 Findings: The data were analyzed in SPSS software (version 19) through a one-way analysis of variance and Scheffe test. According to the results, L-glutamine can significantly reduce the serum levels of pre-inflammatory cytokine, nitric oxide, and CD40 expression in the drug-treated group (group C), compared to the LPS- treated group (group B) (P

Background: Selective IgA deficiency (SIgAD), is known as the most common antibody deficiency. This study, investigated the respiratory disorders among these patients. Method: In this retrospective descriptive study, the data of patients with SIgAD in “Iranian Primary Immunodeficiency Registry” were extracted. Then, demographic characteristics, frequency and type of respiratory disorders, in addition to immunologic findings were gathered and analyzed by SPSS software. Results: One hundred and twenty three patients with SIgAD (78 males/45 females), with the mean age of 18± 9.6 years old were investigated. Respiratory complications (recurrent cold, chronic cough and pneumonia), were the first presentation in 45% of the patients, and respiratory system involvement was detected among 66 patients (54.1%). The prevalence of pneumonia, otitis media and sinusitis, were 33.3%, 12.5% and 20.7%; respectively; which were significantly reduced after the diagnosis (PV

Background: Headache and particularly migraine headaches are considered as a debilitating disease worldwide that can adversely affect the quality of life of children and adults. Various factors can play a critical role in the development of migraine headache attacks. The food allergens are considered as important factors. This study aimed to determine the frequency of food allergy in children with migraine headaches. Methods: Forty patients aged Results: The present study showed 32.5% of our participants had a food allergy. No significant association was detected between sex (p=58) and age (p=0.14) with food allergy. However, the frequency of food allergy was significantly higher in patients aged ≥12 years old (44.4%) than those aged Conclusion: Our findings revealed that about one-third of children with a migraine headache had a food allergy. This frequency was significantly higher in children with migraines than that of the general population based on the results of previous studies. It is recommended that these patients receive a skin allergy test while preparing a strong history of food allergies or when the frequency of migraine attacks does not decrease significantly despite proper prophylaxis.

Background & Objective: Food allergy is an important and increasing problem in children. The aim of this study was to investigate the type and prevalence of food reactions in child care centers of Zanjan city (northwest, Iran). Materials & Methods: This cross-sectional study was performed in 40 kindergartens from Zanjan city. A questionnaire containing information about the occurrence of food reaction, offending food, type of reaction, feeding and birth history, and atopy in the children and their families, was prepared and completed by the parents. Then, the data were gathered and analyzed by SPSS software. Results: In this study 801 children between the ages of 6 months to 5 years were recruited. Two hundred and one reactions (25.1%) were reported. Skin reactions including; urticaria (47.3%) and dermatitis (8%) were registered as the most common problems. Cow's milk (32.3%) was the most offending food. There was significant correlation between age, duration of breast feeding, personal and family history of atopy, and food reactions; however, we did not find any correlation between birth body weight, gender, time of complementary feeding and food reaction. Conclusion: This study showed a high prevalence of food reaction in our region. Therefore, along with confirmatory diagnostic tests, family education for prevention and treatment of children is recommended.

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.

Background & Objective:Allergies are manifested with a variety of signs and symptoms. In this study, the frequencies of asthma symptoms, allergic rhinitis, eczema, and related factors among 6- to 7-year-old schoolchildren were investigated. Materials & Methods:This cross-sectional study was carried out among schoolchildren of 35 elementary schools of Zanjan by using the International Study of Asthma and Allergies in Childhood (ISSAC) questionnaire consisting of the following: asthma symptoms, allergic rhinitis, atopic dermatitis, sex, weight, height, feeding, paracetamol and antibiotic use, maternal education, physical activity, exposure to pets or farm animals, heavy traffic exposure, and parental tobacco use. Data were gathered and analyzed by SPSS software. Results:In this study, 800 children (383 girls and 417 boys) were recruited. The prevalence of wheezing was 28.5% (95% confidence interval [CI] [27, 36]), rhinitis 20% (95% CI [19, 27]), and dermatitis 16.8% (95% CI [13.1, 17.5]). However, the rates of physician-diagnosed asthma, allergic rhinitis, and eczema were 1%, 8.9%, and 4.1%, respectively. The prevalence rates of asthma symptoms and atopic dermatitis were significantly higher in girls than in boys (P=0.01 andPP=0.01). Conclusion:The frequencies of wheezing, rhinitis, and dermatitis among 6- to 7-year-old children were high. Thus, symptoms and history should be considered for the accurate diagnosis and management of children.&nbsp

Type 1 diabetes is a chronic autoimmune disease of beta cells in the islets of Langerhans, which are responsible for making insulin. Even with insulin therapy, inflammatory complications will develop in the long term. The present study examines changes in serum levels of interleukin (IL)-6, IL-17, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, C-peptide, Insulin as well as fasting blood sugar (FBS) in control, diabetic and diabetic treated with curcumin groups. Thirty inbred C57BL /6 mice were randomly divided into three groups of 10 mice: group A consisted of healthy mice receiving citrate buffer, group B included a group of diabetic mice, and group C was a group of diabetic mice treated with curcumin. The cytokine levels were measured in the supernatant of stimulated splenocytes using enzyme -linked immunosorbent assay (ELISA). Radioimmunoassay was used to measure insulin and c-peptide levels. The FBS was measured by an automatic glucometer device. The levels of IL-6, IL-17, and IFN-γ, as well as FBS, was significantly decreased in the treated group with curcumin compared to the diabetic group mice (p

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.

Introduction: Toxic Epidermal Necrolysis (TEN) is a severe disease with high mortality, which can occur following the administration of some drugs such as antibiotics, anticonvulsants and non-steroidal anti-inflammatory drugs (NSAIDs). The condition is rare in children; therefore, providing a therapeutic experience and methods of care can be very helpful in similar cases. Case Presentation: A 32-month-old girl (2.8 years) was admitted at Mousavi Hospital of Zanjan (Iran) presenting weakness, illness, scattered macular lesions on the trunk and extremities, and several blisters on the trunk. He had a history of upper respiratory tract infection and had been administered a diclofenac suppository for fever. All the clinical manifestations appeared after diclofenac administration. The lesions rapidly progressed to extensive cutaneous necrosis with the involvement of more than 70% of the body surface. He was treated with high-dose intravenous immunoglobulin (IVIG), corticosteroid, and conservative management. Fortunately, the child was discharged in good general condition approximately one month after the onset of the illness. Conclusions: Diclofenac can cause TEN in children, even in single doses and in suppositories. The most important prognostic factors include supportive therapy, contact isolation, hand hygiene, and administration of high dose IVIG for at least three days.

Background & Objective:Asthma is the most common inflammatory disorder of respiratory system.The aim of this study was to investigate the prevalence of asthma and association of asthma with anxiety among 13-14 year-old students in Zanjan. Materials & Methods:In this cross sectional study 1500 students were randomly selected by cluster random sampling ; ISSAC questionnaire was filled by face to face interview and patients with asthma were recognized and their anxiety status was also measured using Zung questionnaire. Results:A total of 225 students (15%) had symptoms of mild to moderate asthma. The frequency of anxiety among students with and without asthma was 38.7% and 26.7% respectively. There was a significant correlation between asthma with anxiety (P=0.0001). The odds ratio for anxiety in asthmatic group was 1.73, CI95% (1.16- 2.58). Conclusion:These results showed higher prevalence of asthma and anxiety inadolescents and significant correlation between asthma and anxiety. Keywords:Adolescents,Anxiety,Asthma

Background Constipation is one of the most common disorders in children. The purpose of this study was to compare paraffin and polyethylene glycol (PEG) in the treatment of children with chronic constipation. Materials and Methods This study is a double-blind randomized trial. Total 160 children aged 2-12 years old with chronic constipation attending the pediatric clinic of Mousavi Hospital in Zanjan (Iran) were examined by the same pediatric gastroenterologist. They randomly received PEG solution (1cc/kg/day divided in two doses) or paraffin at the same dose. Patients were assessed regularly once a week up to one month and then monthly until 6 months. Data were analyzed by SPSS version 16 software. Results From children enrolled in the study, 43.1% were boys with mean age 5.27±1.3 years. The male to female ratio in Paraffin and PEG groups was similar (35/45 vs. 34/46; respectively, P-value= 1.27). The mean age of the participants in paraffin group and PEG group were 5.28±1.4 and 5.24±1.9 years, respectively. The good and intermediate response to PEG in comparison to paraffin were 11.3% and 38.8% vs. 23.8% and 35%; respectively (P=0.111). In children lower than 3 years old, the improvement after receiving paraffin was significantly higher (P=0.048). The frequency of adverse effects was similar and didn’t differ significantly between the two groups. Conclusion There was no significant difference between two groups (PEG and Paraffin groups) in terms of gender and adverse effects of drugs. However paraffin had better therapeutic effect among children less than 3 years of age.

Background Intravenous immunoglobulins (IVIg) are the major treatment in inborn errors of immunity (IEI) disorders; However, IVIg infusions show some adverse effects. We aimed to assess the adverse reactions of IVIg infusions. Methods Data of IVIg infusions in IEI patients were collected from 2011 to 2021. Totally, 363 IEI patients received IVIg regularly in Iran entered the study. The adverse reactions are classified regarding their severity and chronicity. Results 22,667 IVIg infusions were performed in the study. 157 patients (43.2%) and 1349 (5.9%) infusions were associated with at least one type of adverse reaction. The highest rates of adverse reactions were seen in severe combined immunodeficiency. Myalgia, chills, headache, fever, and hypotension were the most frequent adverse effects of IVIg. Conclusion The reactions affect almost half of the patients mainly in the first infusions which necessitate the close observation of IEI patients receiving IVIg.

BackgroundThere are differences in the age at menarche in different countries and it seems that in recent decades gradually the age of puberty is declining. The aim of the present study was to determine the age at menarche and its related factors in school girls in Zanjan city, Iran.Materials and MethodsThis cross-sectional study was conducted on 1,500 healthy school girls between 6-17 years old who were selected on the basis of a multistage probability sampling. Age at menarche, birth weight, family size, Body Mass Index (BMI), fast food consumption, and physical activity, were recorded. Data were analyzed using SPSS version 16.0.ResultsOut of 1,500 students, 273 girls (18.2%) had experienced menarche with a mean age of 12.6±1.6 (95% confidence interval [C]: 12.4-12.8), and a median age of 13 years. The prevalence of early menarche, was 10.3%, (95% CI: 6.6%-14.1%). A significant association between menarche and BMI, frequency of fast food consumption and birth rank was observed; however, we didn’t find a significant association between physical activity (P>0.05) and birth weight (P>0.05) with menarche. ConclusionThe mean age of menarche in our study was 12.6±1.6 years old, similar to other studies in Iran, and it was significantly associated with higher BMI.

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.

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.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.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 %).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.

Aim: Comparing cord blood levels of total Creatine kinase (CK) and Creatine kinase MB isoenzyme (CK-MB) in newborns delivered by vaginal delivery and cesarean section. Study Design: Descriptive prospective study. Place and Duration of Study: All neonates delivered from September to October 2012 at the obstetric ward of Mousavi hospital. (Zanjan, Iran). Methodology: Total cord blood CK (CK) and MB isoenzyme (CK-MB) was measured immediately after delivery. Rout of delivery and APGAR (Appearance, Pulse, Grimace, Activity, and Respiration) Score were also assessed and all data were analyzed by using SPSS 16.0 software. Results: One hundred and seventy six newborns were recruited (57.4% male and 42.6% female). We found significant association between serum CK-MB level and rout of delivery. There was no significant association between serum levels of total Ck and