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Oral immunotherapy (OIT) is a novel approach to desensitization and tolerance induction in food allergy patients. This study aimed to design and implement a new wheat OIT protocol, evaluate its efficacy in tolerance induction, and assess specific immunoglobulin-E (IgE) and regulatory T cell changes. From 2015 to 2017, 26 patients with confirmed IgE-mediated hypersensitivity to wheat were treated via oral immunotherapy (OIT). Patients with prior anaphylactic episodes underwent OIT using the rush method. Specific IgE concentrations and the number of regulatory T cells (CD4+ CD25+ FOXP3+ T cells) were measured using Allergy Screen immunoblot assay and flow cytometry, respectively. This study was registered in the Iranian Registry of Clinical Trials (IRCT20181220042066N1). The results revealed success rates of 100% and 93.3% for desensitization and tolerance. Specific IgE was significantly reduced after 12 months of OIT. No significant change in regulatory T cell numbers was observed. In view of the promising findings of this study, the proposed OIT protocol could be viewed as an effective and valuable method to induce tolerance and desensitization in wheat allergic patients.

Introduction and Objectives Considering that no studies have been done on a comprehensive review of Serum sickness-like reactions patients (SSLRs) at a referral center in Iran so far, this study aimed to determine the clinical and laboratory characteristics of children with SSRL in Tehran Children’s Medical Center. Patients The present study was a registry-based study in which the data of 94 SSLRs patients registered in a two-year period were investigated. Confirmation of fever, rash, urticaria, arthralgia / arthritis and history of antibiotic consumption up to three weeks before were the criteria for the diagnosis. Results Fifty-one (54 %) patients were male with mean age of 56 ± 30 months and there was no significant difference in the age of the two genders. The mean onset of symptoms before hospitalization were 3.8 ± 2.7 days (1–14 days); this mean was significantly higher in males than in females (4.6 ± 2.9 versus 2.9 ± 1.7 days, P-value = 0.003). Among antibiotics, Co-amoxiclav and Cefixime antibiotics had the most frequency by 31 % and 33 %, respectively as the most important incidence factor of SSLRs. The mean duration of consumption of culprit medications in the incidence of SSLRs was 5.6 ± 2.9 days with a range of 1–15 days. Conclusions This study showed that among the antibiotics, Co-amoxiclav and Cefixime are more prevalent and a review of prescribing these two antibiotics for the treatment of the children’s infections is essential if this finding is confirmed by other Iranian scholars.

Background Hyper-IgE syndromes (HIES) are distinct diseases characterized by recurrent cutaneous and lung infections, eczema, and elevated serum IgE level. Methods In this study, clinical manifestations, immunologic findings, and genetic studies of all patients with HIES in the Iranian national registry database were evaluated. Results A total of 129 HIES patients with a median age of 14.0 (9.0-24.0) years were followed up for a total of 307.8 patient-years. Genetic studies showed heterozygous STAT3 mutations in 19 patients and homozygous DOCK8 mutation in 16 patients. The mean of National Institutes of Health score in STAT3-deficient patients was higher than in patients with DOCK8 mutation (P = 0.001). It was shown that the presence of pneumatocele and hematologic complication were significantly frequent in STAT3-deficient cases compared to patients with DOCK8 deficiency (P = 0.001 and P = 0.002, respectively). Moreover, the median IgE serum levels were higher in patients with STAT3 gene mutation than in patients with DOCK8 gene mutation (P = 0.02). The eosinophils' count was enhanced in patients with DOCK8 deficiency than in patients with STAT3 gene defects (P = 0.02). Conclusion Specific molecular study of STAT3 and DOCK8 mutations in patients with HIES clinical phenotype could help the physician to definitively characterize the disease. Since HIES showed the highest rate of unsolved combined immunodeficiency, investigation of other genetic and environmental factors could also help in understanding the mechanism of remaining patients as well as providing strategy into therapeutic modalities.

Autosomal polyendocrinopathy syndrome type 1(APS1) is a scarce polyendocrinopathy with autosomal recessive inheritance results from defects in the human autoimmune regulatory (AIRE) gene. In addition to three major manifestations of APS1 including mucocutaneous candidiasis, hypoparathyroidism, and Addison’s disease, ophthalmic problems such as keratoconjunctivitis, dry eye, iridocyclitis, and cataract can be seen in these patients. In this article, we introduced two siblings presented with nail dystrophia, severe photophobia, and keratitis since early childhood which genetic examination revealed single nucleotide T>C translocation in their 2nd exon and heterozygous deletion mutation in their 12th exon.

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 Combined immunodeficiencies (CIDs) are diseases of defective adaptive immunity with diverse clinical phenotypes. Although CIDs are more prevalent in the Middle East than Western countries, the resources for genetic diagnosis are limited. Objectives This study aims to characterize the categories of patients with CIDs in Iran clinically and genetically. Methods Clinical and laboratory data were obtained from 696 patients with CIDs. Patients were subdivided into those with syndromic (344 patients) and nonsyndromic (352 patients) CIDs. Targeted DNA sequencing was performed on 243 (34.9%) patients. Results The overall diagnostic yield of the 243 sequenced patients was 77.8% (189 patients). The clinical diagnosis of hyper-IgE syndrome ( P P = .02), and absence of multiple affected family members ( P = .04) were significantly more frequent in the patients without a genetic diagnosis. An autosomal recessive disease was found in 62.9% of patients, reflecting the high rate of consanguinity in this cohort. Mutations impairing VDJ recombination and DNA repair were the most common underlying causes of CIDs. However, in patients with syndromic CIDs, autosomal recessive mutations in ataxia-telangiectasia mutated (ATM) , autosomal dominant mutations in signal transducer and activator of transcription 3 (STAT3) , and microdeletions in 22q11.21 were the most commonly affected genomic loci. Patients with syndromic CIDs had a significantly lower 5-year survival rate rather than those with nonsyndromic CIDs. Conclusions This study provides proof of principle for the application of targeted next-generation sequencing panels in countries with limited diagnostic resources. The effect of genetic diagnosis on clinical care requires continued improvements in therapeutic resources for these patients.

BACKGROUND Severe combined immunodeficiency (SCID) is a life-threatening pediatric disease. We report on the clinical evaluation, immunological assessment, molecular analysis, and outcomes of SCID patients in a tertiary referral center in Iran. METHODS From January 2006 to December 2015, we performed a prospective cohort study in which initial screening and advanced immunological tests were carried out on patients suspected of having SCID. Genetic analysis was also performed to confirm the diagnosis. RESULTS A total of 63 patients were diagnosed with SCID (43 male [68.3%]). The median age at onset and diagnosis and diagnostic delay were 40 and 110 and 60 days respectively. A total of 49 patients (77.8%) had a history of BCG vaccination, and of these, one-third experienced BCG-associated complications. The most common clinical manifestations were pneumonia, recurrent oral candidiasis, chronic diarrhea, and failure to thrive. Of the thirteen patients who underwent hematopoietic stem cell transplantation, 8 survived and 5 died before they could receive the transplant. Most patients (34.9%) were classified as having T-B-NK+ SCID and had a mutation in the RAG2 or RAG1 gene. CONCLUSIONS Autosomal recessive SCID is the most common type in Iranian patients. Providing high-quality training to physicians and patients' families to reduce the diagnostic delay should be prioritized. It is also important to raise awareness of live vaccination and to expand stem cell donor registries to speed up the transplantation process.

Background A clear picture of interaction of Th1/Th2 cytokines in pathogenesis of chronic spontaneous urticaria (CSU), remains elusive. Impaired IFN-γ production and decreased levels of IL-2 have been reported. The aim of this study was to evaluate the association of Th1 cytokines; IL-2, IL-12 and IFN-γ polymorphisms with CSU. Methods 90 patients with CSU and 140 age-sex matched subjects were included in this study. DNA samples were evaluated through PCR-SSP assay in order to detect single nucleotide polymorphisms of IL-12 (A/C −1188) or (rs3212227), IFN-γ (A/T UTR5644) or (rs2069717) and IL-2 (G/T −330 and G/T +166) or (rs2069762 and rs2069763). Results G allele at −330 at promoter region of IL-2 gene was overrepresented in CSU. Heterozygotes (GT) at this locus and heterozygotes at +166 of IL-2 gene (GT) were more prevalent in CSU group. Additionally, the haplotype GT for loci −330 and +166 of IL-2 gene was powerfully associated with CSU (OR (95%CI) = 57.29 (8.43–112.7)). Conclusions SNP at position −330 and +166 of IL-2 gene are differently expressed in CSU. The haplotype GT of IL-2 at −330 and +166 might confer vulnerability to a number of immunological disorders in Iranian region.

Asthma is a common respiratory disease with huge economic burden leading to activity limitations, morbidity, and mortality. In this study, we aim to investigate the prevalence of Oppositional Defiant Disorder (ODD), Attention Deficit Hyperactivity Disorder (ADHD) and Conduct Disorder (CD) among children with asthma. This case-control study was performed in a pediatric referral health care center (Children's Medical Center in Tehran University of Medical Sciences) in 2017.With random selection, the 80 children with asthma and 92 controls with age range of 5 to 11 years were enrolled in this study. In addition to the demographic information and family history of allergy, asthma symptoms, and control quality evaluated with a validated Childhood Asthma Control Test (C-ACT). The mode of measurement for ADHD, ODD and CD was based on Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) psychiatric scales from clinical interviews conducted by child psychiatrists. Totally, 42.5% and 25% in the case and control groups had ADHD respectively with significant difference (p=0.01). Also, 25% and 5.4% in the case and control groups had ODD respectively with significant difference (p=0.001). But conduct disorder was 10% and 10.9% in case and control groups respectively without significant difference (p=0.8). Children with asthma were associated with exhibiting ADHD and ODD but not CD. Therefore, appropriate evaluation and treatment are needed for asthmatic children with attention-deficit and ODD symptoms. Besides, further research is needed to determine the etiological approach towards ADHD, ODD and asthma.

Hyperimmunoglobulin E syndrome (HIGE) is considered as a phagocytic or a newly classified complex and heterogeneous primary immunodeficiency disease with symptoms such as increased levels of immunoglobulin E, eczema, and, recurrent lung and skin infections. In this paper, we have presented a rare case of this syndrome. A 9-year-old Iranian girl presented with a history of pruritic maculopapular rash who was eventually diagnosed as a case of HIGE. In her recent admission, she had dysphonia, stridor and huge cauliflower cutaneous lesions on her neck, finger and vocal cords, which did not respond to intravenous antibiotics, and ultimately required surgical removal.

Fractional exhaled nitric oxide (FeNO) is a noninvasive marker of inflammation, used for monitoring asthma. The aim of this study was to compare FeNO, asthma control test (ACT), and lung function test (spirometry) in children aged 8-15 years. This observational, cross-sectional study was performed on76 asthmatic children (age, 8-15 years), who were referred to the Department of Immunology and Allergy, Children's Medical Center, Tehran, Iran during 2012-2013. Patients were matched for sex and age. The recruited patients were selected via consecutive sampling. FeNO was measured with a portable electrochemical analyzer and forced spirometry was performed according to the American Thoracic Society (ATS) guidelines. The ACT questionnaire was used and completed for all the patients. The mean FeNO was 28.5±29.1 ppb, and the mean ACT score was 19.8±3.6. FeNO was significantly correlated with forced expiratory volume (FEV1) (r, 0.232; p=0.049) or 25-75% maximum expiratory flow (MEF 25-75) (r, -0.304; p=0.009). FeNO showed no significant correlation with ACT score or FEV1/forced vital capacity (FVC) (p>0.05). Additionally, there was no significant correlation between FeNO and changes in FEV1 and MEF 25-75% before and after the administration of bronchodilators (p>0.05). To improve asthma control, childhood ACT, FeNO, and spirometric tests can be used as complementary tools in clinical practice to detect children with poorly controlled asthma.

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 Chronic respiratory diseases such as asthma and allergic rhinitis (AR) are a major public health problem in developing countries including those in the Middle East. However, to date, there is a paucity of information related to physician-diagnosed AR in this region. The Allergies in Middle East Survey was undertaken to help clarify and broaden the understanding of physician-diagnosed AR across Egypt, Iran, Lebanon, Saudi Arabia, and the United Arab Emirates. The survey explores the frequency of physician-diagnosed AR, prevalence and types of associated symptoms, the impact on quality of life (QOL), current treatment practices, and therapy expectations. Methods In total, 7411 households in five countries (Egypt, Lebanon, Saudi Arabia, Iran and the United Arab Emirates) were screened to identify individuals that were ≥4 years old with a physician diagnosis of AR and either symptoms and/or treatment in the past 12 months. A total of 501 respondents from the five countries completed the survey. Standardized questionnaires were used to make comparisons across the regions; however, the data collection procedures were tailored for each country. The sample was probability based to ensure valid statistical inference to the population. Results Ten percent of the Middle East population surveyed had a physician diagnosis of AR, with 65% of respondents stating that their allergies were intermittent in nature. An otolaryngologist or allergist diagnosed the majority of the individuals surveyed. Runny nose, nasal and throat itching, postnasal drip, and nasal congestion or stuffed up nose were the most common and bothersome symptoms of AR. The majority of survey participants (58% of the overall survey population) with AR reported that the condition had an impact on their daily private and professional life. Seventy-two percent of adults reported that their AR symptoms limited their work/school activities and 35% reported that their AR interfered with and caused them to miss work or school within the past 12 months. One factor, in addition to the outward AR symptoms, that could have contributed to these function impairments may have been sleep disturbances. Although a secondary symptom to AR, sleep disturbances (difficulty getting to sleep, waking up during the night or lack of a good night's sleep) were shown in this survey to be extremely troubling in ∼15% of AR sufferers. In the past year >90% of patients reported taking a medication of any type for their AR, with nearly a 4:1 ratio of patients taking a prescription medication versus an over-the-counter (OTC) medication in the past 4 weeks. Over 75% of survey respondents reported taking an intranasal corticosteroid (INCS) in the last 4 weeks and the satisfaction rate of INCS medications was similar to that reported for OTC medications. The most common reasons cited for dissatisfaction with INCS medications were inadequate effectiveness, bothersome side effects (e.g., unpleasant taste and retrograde drainage into the pharynx), decreased effectiveness with chronic use, and failure to provide 24-hour relief. Conclusion These data show that AR is common in the Middle East region as elsewhere in the world. Many patients with AR in Middle East region suffer from their symptoms (e.g., runny nose, nasal itching, nasal congestion, postnasal drip, and other symptoms) on all or most days during the times of the year that their allergies are worst. These symptoms have been shown to reduce QOL and performance at work/school to a significant degree. Additionally, the survey data underscore a considerable treatment gap with current therapies for AR and that many AR patients still have not found adequate effectiveness with currently available medications. Thus, through identification of disease impact on the Middle East population and highlighting treatment gaps, clinicians in the Middle East may better understand and treat AR, leading to improvements in overall patient satisfaction and QOL.

Atopic dermatitis is an inflammatory skin disease in which both genetic and environmental factors interact to determine the susceptibility and severity of the disease.The aim of this study was to determine the association between atopic dermatitis and IL-10 and TGF-β1 gene polymorphisms.The allele and genotype frequencies of genes encoding for IL-10 and TGF-β1 were investigated in 89 patients with atopic dermatitis in comparison with 138 in the control group using the PCR-SSP method.A significant increase was found in the frequency of the TGF-β1 codon 10/C allele among patients (p0.001, OR=6.77), whereas a significant decrease was observed in the frequency of the T allele at the same position (p0.001, OR=0.14). The frequency of the TGF-β1 codon 25/G allele in the control group was significantly higher than among patients (p0.001, OR=0.08). A significant positive correlation was seen between CC (p0.001, OR=15.10) and CG (p0.001) genotypes and AD at codons 10 and 25, respectively. The most frequent haplotypes among patients was TGF-β1 CG which was significantly higher than in the control subjects (50% in patients vs. 39.9% in controls, p=0.042). A significant increase was found in the frequency of TGF-β CC (36% in patients vs. 7.6% in controls, p0.001) and TC (14% in patients vs. 0% in controls, p0.001) haplotypes among patients compared to controls. By contrast, the TGF-β1 TG haplotype was significantly lower in patients than controls (0% in patients vs. 52.5% in controls, p0.001). There were no significant differences in the frequency of alleles, genotypes and haplotypes of the IL-10 gene.We found a strong association between the polymorphisms of the TGF-β1 gene at codon 10 and codon 25 positions and atopic dermatitis.

This study was performed to evaluate association of gene polymorphisms among proinflammatory cytokines and susceptibility to chronic idiopathic urticaria (CIU).Ninety patients with prolonged urticaria more than 6 weeks were included as case group. Single nucleotide polymorphisms (SNPs) of IL-6 (G/C -174, G/A nt565) and TNF-α (G/A -308, G/A -238) were evaluated, using polymerase chain reaction (PCR); and the results were compared to the control group.G allele was significantly higher in the patients at locus of -238 of promoter of TNF-α gene (p0.001). Frequency of following genotypes were significantly lower in patients with CIU, compared to controls: AG at -308 and GA at -238 of TNF-α gene (p0.05 and p0.001, respectively), CG at -174 and GG at +565 of IL-6 gene (p0.05). Additionally, following genotypes were more common among patients with CIU: GG at -308 and -238 of TNF-α gene (p0.05 and p0.001, respectively), GG at -174 and GA at +565 of IL-6 gene (p0.05).Pro-inflammatory cytokine gene polymorphisms can affect susceptibility to CIU. TNF-α promoter polymorphisms as well as IL-6 gene polymorphisms are associated with CIU.

Background Interleukin-1 (IL-1) seems to have an important role in early reactions towards microbes, while its genetic variability could affect this role in atopic patients who have a distressed immunity towards dermatological infections. Methods Eighty-nine patients with atopic dermatitis (AD), who were referred to a main referral paediatric hospital, were enrolled in this study. Single nucleotide polymorphisms (SNP) of the following IL-1 cluster genes were assessed in this group of patients: IL-1α −889, IL-1β −511, IL-1β +3962, IL-1R Pst-I 1970, and IL-1RA Mspa-I 11100. The results were compared with a group of 140 healthy subjects from the same region. Results Fourteen percent of the controls had TT homozygous genotype in IL-1R at position Pst-I 1970, while only 2% of the patients with AD had this genotype ( p = 0.005, OR: 0.14, 95%CI: 0.02–0.64). The CC homozygous genotype was the most common genotype in IL-1α position −889 and IL-1β at position +3962 in both groups of patients with AD and the controls, while the TC heterozygous genotype was the most common genotype in IL-1β at position −511 and IL-1R at position Pst-I 1970, with no significant difference between the two groups. Conclusions This study showed a significant negative association in the IL-1R Mspa-I 11100 TT homozygous genotype in the patients with AD.

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.

There is a growing concern regarding continuous risk of emerging a new influenza pandemic. It is highlighted the need for novel vaccination techniques that quickly and effectively employed to respond to such threats. Although, DNA vaccine is a simple and effective approach to induce antigen specific immune responses, their potency requires further improvement. DNA vaccine encoding conserved antigen of influenza virus could provide protection in various animal models. Therefore, we constructed a plasmid vector encoding M2e-HSP70c sequences, pcDNA/MHc, as a candidate for universal influenza vaccine. The expression of newly constructed vectors was verified by transient transfection of mammalian cells (HEK293T cell line) and western blot analysis using commercial antibodies. Mice were injected subcutaneously (s.c.) by the help of electroporation (IEP) in the footpad area and boosted without IEP with 100 μg of constructed vector. Furthermore, the potency of this construct to provoke humoral immune responses and its protectivity against lethal dose of viral challenge were evaluated. Based on our study, the fusion construct was immunogenic in mice and was able to confer both protection against lethal challenge of H1N1 virus and reduce viral load in lung homogenates of the infected mice.

IgA deficiency (IGAD) is the most common primary antibody deficiency. Although many affected individuals have no apparent symptom, selected patients suffer from recurrent mucosal infections, allergies, and autoimmune diseases. We aimed to investigate the clinical features in relation to immune function of Iranian patients with symptomatic IGAD. Thirty-seven patients (21 male and 16 female), aged 4–32 years, were evaluated in this study. Patients were followed for a total of 131 patient years with a mean follow-up of 3.5 years per patient. The most prevalent presentations were recurrent infections occurring in 27 subjects, followed by allergy in eight cases and autoimmunity in two patients. However, during the follow-up period, 35 patients developed infections in respiratory and gastrointestinal tracts, necessitating medical care. Apart from infections, allergy was the most frequent complaint (31 cases); the major features were asthma, atopic dermatitis, and allergic rhinoconjunctivitis. Autoimmune diseases were documented in ten cases; thyroiditis was the most common. In 31 patients who received unconjugated pneumococcal polyvalent vaccine, antibody response against polysaccharide antigen was measured before and 28 days after vaccination. One fourth of vaccinated patients were hyporesponsive to vaccine; four of these patients developed bronchiectasis. The patients with IGAD were classified into two groups: group 1 (14 cases) consisted of patients with IGAD and other associated immune defects, such as immunoglobulin G (IgG) subclass deficiency and defective specific antibody production. Group 2 (23 cases) had isolated IGAD without other immunological abnormalities. There was a significantly increased number of lower respiratory tract infections in group 1 compared with group 2 (P = 0.006). Moreover, four patients of group 1 had bronchiectasis whereas none of the patients in group 2 developed this complication (P = 0.015). Subclassification of IGAD regarding the existence of associated immune defects is useful in terms of morbidity and planning for medical care. IgA-deficient patients with concomitant immune defects such as defects in specific antibody production have higher rates of recurrent infections and bronchiectasis, which necessitates more effective monitoring.

Common variable immunodeficiency (CVID) is a heterogeneous group of disorders, characterized by decreased serum immunoglobulin levels, and increased susceptibility to recurrent bacterial infections, malignancies, and autoimmune disorders. In this report, 2 siblings with CVID who developed Hodgkin lymphoma are presented: a 16-year-old girl at stage IIB and her 12-year-old brother at stage IIIB of Hodgkin lymphoma. Their father and 1 uncle were also affected by the same cancer with no immunodeficiency state. The presence of lymphoma should be considered in the patients with CVID, especially in those with family history of malignancies.

PROBLEM:Primary Immunodeficiency Disorders (PiD) are a heterogeneous group of genetic disorders, with different modes of inheritance. This study was accomplished in order to determine the frequency of consanguineous marriages in the families of patients with PiD. METHOD:In this study, the records 515 Iranian PiD patients were reviewed during a 25-year period. RESULTS:The mean proportion of consanguineous marriages was 65.6% among PiD patients, while the overall rate was 38.6% in the country. The rate of consanguinity was 77.8% in cellular immunodeficiencies, 75.8% in combined immunodeficiencies, 72.5% in defects of phagocytic function, 58.6% in other immunodefiiencies, 54.1% in predominantly antibody deficiencies, and 50% in complement deficiencies. Moreover all patients with immunodeficiency associated with other diseases had consanguineous parents. Such marriages were most common in the parents of patients with Chediak-Higashi syndrome, severe combined immunodeficiencies, primary CD4 deficiency, ataxia-telangiectasia, selective IgG class deficiencies, chronic granulomatous disease, and Schwachman syndrome. CONCLUSIONS:It is important to inform the general population about the dangers of consanguinity, which is very common in some areas such as Iran. Premarital examination to avoid genetic diseases could be suggested, especially in a community where the rate of consanguineous marriage is high.

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency characterized by reduced levels of all major immunoglobuline classes and recurrent c infections. The risk of non-Hodgkin's lymphoma (NHL) among patients with CVID was found to be increased in different studies. Mucosa-associated lymphoid tissue (MALT) lymphomas are a recently recognized sub-set of low-grade B-cell NHL composed of marginal zone-related cells. MALT lymphomas appear in the lymphoid tissues as a result of chronic inflammatory or autoimmune stimulation. This study briefly reviews previously published cases and reports a patient suffering from CVID with a history of chronic diarrhea and recurrent sinopulmonary infections. Despite treatment with intravenous immunoglobulin, chronic cough and wheezing progressed. Open lung biopsy showed a MALT lymphoma. Although a rare complication, pulmonary low grade B-cell lymphoma is a diagnosis that must be kept in mind in CVID patients with chronic pulmonary symptoms unresponsive to conventional therapies.

Inherited neutropenia is characterized by a decrease in the absolute number of circulating neutrophils and an increased susceptibility to infections. The current study was performed to determine the clinical and laboratory findings of Iranian patients with inherited neutropenias. Records of 26 patients (14 male, 12 female) with inherited neutropenia were reviewed in this study. The patients had been referred to Children's Medical Center, a referral center for immunodeficiency disorders in Iran, during a 22-year period (1981-2003). Primary immunodeficiency disorders of these patients were as follows: cyclic neutropenia (8 patients), Shwachman-Diamond syndrome (7 patients), Kostmann syndrome (6 patients), and Chediak-Higashi syndrome (5 patients). The mean absolute neutrophil count of patients was 398.2 +/- 259.3 cells/mm (range 74-1,152/mm) at the first visit. Twenty-one patients showed severe, four moderate, and one mild neutropenia. Sixteen of these patients had leukopenia, seven anemia, two thrombocytopenia, and one monocytosis. The most common presenting complaints in these patients were oral ulcer, otitis, pneumonia, diarrhea, cutaneous abscess, and oral candidiasis. The patients first manifested symptoms of infection suggesting neutropenia at a median age of 7.5 months (range 1 month to 10 years). During follow-up, respiratory infections developed in 24 cases, oral manifestations in 20 patients. The most common infections, in descending order of frequency, were otitis media, abscesses, pneumonia, oral ulcers, acute diarrhea, cutaneous infections, oral candidiasis, and periodontitis. Less frequent infections were sinusitis, cystitis, conjunctivitis, meningitis, and osteomyelitis. Nonspecific symptoms (hepatomegaly and splenomegaly) were also detected in 10 patients and 1 patient, respectively. Three patients died of recurrent infections. The infectious manifestations both at presentation and during follow-up in inherited neutropenia were similar. Although inherited neutropenias are rare, recurrent infections always deserves further evaluation for detecting such disorders.

Primary immunodeficiency disorders (PID) are a group of hereditary disorders characterized by an increased susceptibility to severe and recurrent infections, autoimmunity, lymphoproliferative disorders, and malignancy.To evaluate the demographic and clinical data of PID patients diagnosed in a referral pediatric hospital.All PID cases with a confirmed diagnosis, according to the criteria of International Union of Immunological Societies, who were referred to the Children's Medical Center in Tehran, Iran, between March 2006 and March 2013 were enrolled in this retrospective cohort study.Three-hundred and seven PID patients were investigated. Predominantly antibody deficiencies were the most common group of PID observed in 118 cases (38.4%), followed by the well-defined syndromes with immunodeficiency in 52 (16.9%), congenital defects of phagocyte in 45 (14.7%), combined immunodeficiencies in 36 (11.7%), autoinflammatory disorders in 34 (11.4%), immune dysregulation in 11 (3.6%), complement deficiencies in 7 (2.3%), and defects in innate immunity in 3 (1%). Selective IgA deficiency was the most prevalent disorder which affected 46 individuals (14.9%). The median diagnostic delay was 15 months.Increased awareness and availability of diagnostic tests could result in the better recognition of more undiagnosed PID cases and a decrease in diagnostic delay.

Common variable immune deficiency (CVID) is the most frequent form of symptomatic primary immunodeficiency disease, characterized by hypogammaglobulinemia, recurrent infections and increased predisposition to autoimmunity and malignancies. The aim of this study was to reconsider important points of previously performed studies on Iranian CVID patients diagnosed and followed from 1984 to 2013.Diagnosis was made using approved criteria including reductions of serum levels of immunoglobulins and exclusion of well-known single gene defects in individuals with an age4 years and evidence of specific antibody deficiency.Detailed information on demographic data, survival rates, clinical phenotypes, immunologic and genetic data and treatment of 173 patients are provided. The early onset presentation (74.5%) and rate of consanguineous marriage (61.2%) were considerably higher in our cohort. Our study revealed clinically related correlations regarding consanguinity, the population of naïve CD4(+) T cells and switched-memory B cells, cytokine levels and special genetic factors (including HLA and AID genes).Despite current efforts, more comprehensive studies are needed, especially for classification and investigation of the genetic background and prognostic factors for patients with CVID in order to better managment and followup of patinets.

Zinc deficiency, which is common in patients with cystic fibrosis (CF), can lead to several complications that may increase the number of hospital admissions in this group of patients. As supplementary zinc can prevent such complications, this study was performed to evaluate the effect of supplementary zinc on body mass index (BMI), forced expiratory volume in one second (FEV1) and number of hospitalizations in CF patients. In this study, 30 children with CF, who were referred to the Digestive Diseases Clinic of the Children's Medical Center in Tehran, were enrolled. Supplementary zinc of 2 mg/kg per day was administered to all patients. Serum level of zinc, alkaline phosphatase, and albumin as well as BMI, FEV1, and number of hospitalizations were compared before and after zinc administration. Height (p0.001), weight (p0.001) and BMI (p=0.001) were significantly increased after zinc, while the number of hospitalizations was significantly decreased (p=0.023). In contrast to patients with normal pulmonary function tests who received supplement therapy, BMI was not increased in those with abnormal pulmonary function after supplementary zinc. Supplementary zinc can increase BMI in CF patients, mostly in those with normal pulmonary function. While supplementary zinc may decrease the number of hospitalizations, other factors can also influence the hospitalization number.

This cross-sectional study was designed to estimate the frequency of asthma in patients with atopic dermatitis (AD), and its related factors.The study population consisted of 236 patients with AD who were referred to Children Medical Center in 1997-2002 and their diagnosis was based on HanifinRajka criteria. Severity of AD was categorized based on Severity Scoring of Atopic Dermatitis (SCORAD) index. Asthma was diagnosed with medical history and clinical examination (three or more episodes of wheezing and/or dyspnea and/or cough after 1 year old). The patients were divided in two groups according to having or not having asthma.The mean age of patients with AD was 38.67+/-2.68 month and the mean age at onset of asthma was 20+/-2.5 month. The frequency of asthma in AD patients was 27.5%. The mean of SCORAD in nonasthmatic patients was 52.27 +/- 2.52 and in asthmatic patients was 56.2+/- 4.2 (P= 0.4). The mean of duration of breastfeeding in asthmatic patients was 12.2+/-1.6 month and in non-asthmatic patients was 11.16+/-6.3 month (P = 0.87). There was no significant difference between asthmatic patients and others in serum IgE levels (P = 0.65) and blood eosinophil count. (P = 0.49).These results confirmed that development of asthma in patients with AD is more than normal population and AD can be a significant predisposing factor to developing asthma but the causative factors are not clear.

Tumor necrosis factor-alpha (TNF-α) could be considered as potential biomarkers in atopic dermatitis (AD), while its level could be influenced by cytokine single gene polymorphisms (SNP). This study was performed in 89 pediatric patients with AD and 137 controls to assess polymorphisms of the TNF-α gene at positions -308 and -238, using the polymerase chain reaction and the sequence-specific primers method. The highest positive allelic association that made the patients susceptible to AD was seen for TNF-α -238/G ( p

Common variable immunodeficiency (CVID) is a highly heterogeneous disease with an unpredictable pattern. CVID appears to have an immunologic and clinical phenotype similar to some hereditary humoral immunodeficiencies, including X-linked lymphoproliferative disease (XLP).The differential diagnosis of CVID and XLP is clinically of importance, because the two diseases have markedly different prognoses and treatment. The recent identification of the XLP gene, known asSH2D1A, has permitted a definitive diagnosis of XLP. In this report, we describe a male patient with XLP who initially received a diagnosis of CVID and developed a fatal course. Using genetic analysis, we confirmed that the patient harbored theSH2D1A gene mutation.The results support the notion that the possibility of aSH2D1A gene mutation should be considered in hypogammaglobulinemic male patients before a diagnosis of CVID is made. Int J Hematol.

Despite preliminary evidence, the role of probiotic and synbiotic in treatment of the atopic dermatitis has shown varying results. We aimed to evaluate whether synbiotic supplementation decrease severity of atopic dermatitis (AD) in childhood. In a randomized double blind-placebo controlled trial, we evaluated the synbiotic supplementation efficiency on the treatment of atopic dermatitis. Infants aged 1-36 months with moderate to severe atopic dermatitis were randomized (n=41) and received either synbiotic (probiotic plus prebiotic) (n=20) or placebo (n=21) daily as a powder for two months. Emollient (Eucerin) and topical corticosteroid (Hydrocortisone) were permitted. Children were scored for severity of atopic dermatitis (SCORAD). Also allergen Skin Prick Tests (SPT), IgE blood level and eosinophil count were measured at first visit. Patients' SCORAD were reevaluated at the end of intervention. We followed 36 out of 41 subjects for two months (drop out rate = 9%). In the whole group, the mean Total SCORAD (at base line 40.93) decreased by 56% (p=0.00). The mean Objective SCORAD (at base line 31.29) decreased by 53% (p=0.00). There was no significant difference in the mean decrease of total SCORAD between placebo (22.3) and synbiotic groups (24.2). There was also no difference between two intervention groups in the mean decrease of total SCORAD regarding to different demographic, clinical and para clinical subgroups. This study could not confirm synbiotic as an effective treatment for childhood atopic dermatitis and further studies are needed. These findings challenge the role of synbiotics in the treatment of childhood atopic dermatitis.

UNLABELLED Patients with CVID are at greater risk of developing lung complications than patients with XLA because of delayed diagnosis and possible immune dysregulation. Early diagnosis and appropriate treatment reduces the incidence of pulmonary infections in both groups of patients. However, CVID patients are prone to progressive lung disease despite optimal immunoglobulin therapy. BACKGROUND AND OBJECTIVE Pulmonary disease is the most common complication in patients with common variable immunodeficiency (CVID) or X-linked agammaglobulinaemia (XLA). Pulmonary disease may progress despite immunoglobulin replacement therapy. In this study pulmonary complications were compared in patients with CVID or XLA. METHODS Pulmonary complications were evaluated in 115 patients (76 with CVID and 39 with XLA) by reviewing hospital records of chest infections, pulmonary function tests and high-resolution CT scans. RESULTS Thirty-two patients with XLA (82%) presented with 59 episodes of pneumonia before diagnosis, whereas 15 patients (38.4%) experienced pneumonia after immunoglobulin replacement therapy (1.67 vs 0.45 episodes per patient per year). Among the CVID patients, 196 episodes of pneumonia were documented in 59 patients (77.6%) before diagnosis, while 36 patients (47.3%) experienced pneumonia after therapy (1.11 vs 0.58 episodes of pneumonia per patient per year). Forty-seven (41%) patients (38 with CVID and 9 with XLA) developed chronic lung disease. The CVID patients developed more complications, including bronchiectasis and lymphoid interstitial pneumonitis, than the XLA patients. CONCLUSIONS Patients with CVID had a greater likelihood of developing lung disease, possibly due to delayed diagnosis and immune dysregulation, as compared with XLA patients. Early diagnosis of patients with primary antibody deficiencies and adequate i.v. immunoglobulin replacement therapy substantially reduces the number of pulmonary infections. However, CVID patients are prone to progression of lung disease despite optimal immunoglobulin therapy because of the nature of the disease. This important issue should be addressed in further studies.

Severe Combined Immunodeficiency (SCID) consists of a heterogeneous group of genetic disorders characterized by an arrest in T lymphocyte development which is variably associated with an abnormal differentiation of B and NK cells. In order to depict the clinical state of Iranian patients with SCID, records of forty patients were reviewed. Patients were classified based on the flow cytometry data in two groups of B- and B+. In thirty two families (80%) parents were consanguine and in 17 families (50%) there were affected members other than proband. We showed that autosomal forms of SCID might be more frequent due to higher rate of consanguineous marriages. Alongside several infective complications, complicated Bacillus Calmette-Guerin (BCG) vaccination was documented in 18 cases (45%) following the routine vaccination at birth. BCG immunization is still a part of standard vaccination for newborns in developing countries; whereas in communities with a better health condition it could be held for a few months and performed for kids whose immune system sounds intact. We discuss where consanguine mating is common, a test of screening should be run timely. A complete blood count of cord blood could reveal lymphocytopenia at birth; this helps early diagnosis. Genetic consultation would help the families with affected members preventing new SCID offspring.

Objective:One hundred and nine patients with primary antibody deficiencies were selected in order to determine the frequency of ENT complications.Method:Demographic information and ENT medical histories were collected for each patient. Duration of study for each patient was divided into two periods of before diagnosis and after diagnosis and the initiation of treatment.Results:Eighty-two of 109 patients (75.2 per cent) experienced ENT infections during the course of the disease (63: otitis media, 75: sinusitis and nine: mastoiditis). At the time of diagnosis, 52 (47.7 per cent) out of 109 patients presented with an ENT symptom. The frequencies of episodes were 27 for sinusitis and 25 for otitis media (one complicated with mastoiditis). After immunoglobulin replacement therapy the incidence of otitis media was reduced from 1.75 before treatment to 0.39 after treatment per patient per year (p = 0.008). The incidence of sinusitis also significantly decreased from 2.38 to 0.78 (p value = 0.011).Conclusion:ENT infections are common medical problems in primary antibody deficiency patients. Persistent and recurrent ENT infections should be suspected as originating from a possible underlying immunodeficiency.

In the management and evaluation of asthma, simple instruments for measurements of peak expiratory flow rate (PEFR) are necessary. The aim of this study was to determine normal PEFR of the healthy children in Babol, Iran. This study was randomly done on 1050 students (primary and secondary schools) in Babol. Mini-Wright peak flow meter was used for measurement of PEFR. The range of age, weight and height were defined. Information was statistically analyzed by SPSS, T- Test and R2 and due to formula with regression. Mean age of 1050 students (525 male and 525 female) who participated in this study was 10.26 years. The mean of PEFR was 262.35±71.97 L/Min. Obtained PEFR with all anthropometrics variants indicate a high correlation. Correlation between PEFR and height was more significant and between PEFR and weight was lower, and according to importance of height and age, formulas suggested for prediction of PEFR in females {(age×4/8)+ (height×0/6)-25)} and in males ({(age×1/7)+ (height×2/1)-208)}. The results of this study can determine normal PEFR and it can be useful for treatment and monitoring of children with asthma who live in this region.

Primary antibody deficiencies are the most frequent primary immunodeficiency disorders. Bronchiectasis as a feature of these disorders may be developed due to some factors such alpha-1- antitrypsin deficiency. In order to determine the prevalence of two common alpha-1-antitrypsin deficiency alleles (PI*Z and PI*S) in Iranian patients with antibody deficiency, this study was performed. The prevalence of PI*M, PI*S, and PI*Z allele combinations was determined in 40 patients with primary antibody deficiency (with and without bronchiectasis) and compared with 60 healthy control subjects. Phenotyping was performed by isoelectric focusing. The phenotype frequencies among patients were as follow: M in 92.5%, S in 2.5% and Z in 5%. There was not any significant difference in distribution of alleles or phenotypes between patients and control subjects. Moreover, no significant difference was found between patients with and without bronchiectasis. We did not find evidence to support an association between alpha-1-antitrypsin phenotypes and primary antibody deficiencies in a small, controlled study. Larger studies will be required to clarify the relationship between alpha-1-antitrypsin genotype and susceptibility to bronchiectasis in patients with antibody deficiency.

The primary immunodeficiency (PI) disorders are abnormalities in development and maturation of the immune system. Individuals with PI disease may experience frequent infections, which limit their abilities to exhibit physical and psychological well-being secondary to their illness. In this survey we compared health-related quality of life of primary immune deficient patients with healthy children. The case-control study was designed for patients with PI disease who were referred to Children Medical Center in 2004-2005. Demographic information was taken and Pediatric Quality Of Life (PEDQOL) questionnaire were filled for 50 PI patients and 100 healthy children. The mean age in PI patients was 12.62+/- 3.65 (range from 8 to 18) years and in the control group was 11.04+/- 3.3 years. In PI patients 68% were male and 32% female .Most patients with PI disease had a diagnosis of common variable immunodeficiency (54%) or X-linked agammaglobulinemia (24%). Patients with PI disease had great limitations in physical functioning and psychological well-being (p0.001 and p0.001 respectively) compared with children without a chronic health condition. Patients had lower PEDQOL scores in all age groups compared with normal sample (p0.001). Long duration of disease significantly correlated with low psychological score. (r =-3.23. P= 0.03) Children with PI disease experience poorer health related quality of life than healthy children, indicating more attention should be paid to early diagnosis and treatment of PI disease, as well as more attention to their social limitation. PI patients may need psychological consultation for better coping with their illness.

There are few reports about congenital indifference to pain or Hereditary and Sensory Autonomic Neuropathy (HSAN). Several investigations for pathophysiology of this syndrome have been performed and different classifications about it. In this report we present a case of HSAN type II with general absence of pain and self amputations and leprosy–like damage of extremities which was suspected to be phagocytic immunodeficiency due to past history of repeated ulcer and abscess formation.

Ataxia-telangiectasia is a multisystem disorder characterized by progressive neurologic impairment, variable immunodeficiency, impaired organ maturation, x-ray hypersensitivity, oculocutaneous telangiectasia, and a predisposition to malignancy. To evaluate clinical and immunologic features of Iranian patients with ataxia-telangiectasia, the records of 104 patients with ataxia-telangiectasia (54 male, 50 female) with the age range of 1.6-23.5 years were reviewed. The Iranian Primary Immunodeficiency Registry was used as the data source. Progressive ataxia was seen in all the patients. Other symptoms were eye movement disorders (n = 84), slurred speech (n = 70), mental retardation (n = 10), and ocular (n = 87) and cutaneous (n = 73) telangiectasia. Three patients developed leukemia and lymphoma, and 17 patients had family history of malignancy. Positive correlation was seen between clinical immunologic symptoms and immunoglobulin deficiencies (P = 0.004). The predominant infections were sinopulmonary and acute and recurrent infections (78 cases). Infections included pneumonia (56 patients), otitis media (34 patients), and sinusitis (50 patients). Average serum alpha-fetoprotein level was 149 +/- 137 ng/dL. The incidence of ataxia-telangiectasia in Iran is high, possibly due to familial marriages. Treatment should be focused on supportive management to prolong survival.

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.

In order to determine the clinical and laboratory findings of Iranian patients with presumed hyper-immunoglobulin E syndrome (HIES), the medical records of 22 patients from 21 unrelated families, who had been registered in the Iranian Primary Immunodeficiency Registry, were observed. The median age of patients at the time of first symptom and at the time of diagnosis was 1 month and 52.5 months, respectively, with a median diagnosis delay of 70 months. 13 families had consanguineous marriages. IgE level was higher than 2000 IU/ml in all patients, ranging from >2000 to 80,000 IU/ml. The most commonly occurring manifestations were: eczema and dermatitis, pneumonia, upper respiratory tract infections, cutaneous abscesses, diarrhoea, deep abscesses, and otitis media. Other less frequent manifestations were: mucocutaneous candidiasis, sinusitis, cutaneous ulcers, Molluscum contagiosum, herpetic keratitis, onychomycosis, conjunctivitis, septic arthritis, and meningitis. Five patients were complicated by bronchiectasis due to recurrent pneumonia and 5 patients died because of severe infections and malignancy. The HIES is a multisystem disorder that affects especially cutaneous, respiratory, skeletal and the immune system. Although HIES is a rare condition, the recurrent infections should always raise a suspicion, which deserves further evaluation for detecting the syndrome.

Primary immunodeficiency disorders (PID) are a heterogeneous group of diseases, characterized by an increased susceptibility to infections. A total of 930 patients (573 males and 357 females) are registered in Iranian PID Registry (IPIDR) during three decades. Predominantly antibody deficiencies were the most common (38.4%), followed by congenital defects of phagocyte number and/or function (28.3%), other well-defined immunodeficiency syndromes (17.7%), combined T- and B-cell immunodeficiencies (11.0%), complement deficiencies (2.4%), and diseases of immune dysregulation (2.3%). Common variable immunodeficiency was the most frequent disorder (20.8%), followed by chronic granulomatous disease, ataxia-telangiectasia, btk deficiency, selective IgA deficiency, and T-B-severe combined immunodeficiency. The frequency of other PID disorders was less than 50 in number (

Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder, which presents with hypogammaglobulinemia and recurrent bacterial infections. Patients with CVID have frequent and severe episodes of pneumonia. The standard intravenous immunoglobulins (IVIG) therapy has led to the reduction of pulmonary infections in these patients. The aim of this study was to evaluate the effectiveness of IVIG treatment in reducing the incidence of pneumonia in patients with CVID.Twenty six Iranian patients with CVID whose diseases had been diagnosed at the Children Medical Center and had received regular IVIG for at least 9 months were selected. The numbers of episodes of pneumonia and hospital admissions were documented before and during treatment with IVIG.Of 26 patients with CVID, 80.5% had experienced pneumonia at least once before receiving immunoglobulin and 88.5% required hospital admission. After starting treatment with IVIG (mean treatment period, 41.5 +/- 35.4 months), the annual incidence of pneumonia significantly decreased from 80.5% to 34.6% (p=0.0017), and the rate of hospitalization from 88.5% to 46% (p=0.0025) . The incidence of pneumonia requiring treatment or hospitalization fell from 3.4 to 0.7 per year (p0.0005).Regular IVIG therapy can significantly reduce the incidence of pneumonia and hospital admission due to infections in patients with CVID.

Neutropenia may occur in some of the primary immunodeficiency disorders. We reviewed the records of 56 neutropenic patients. The most common disorders were Shwachman-Diamond syndrome, cyclic neutropenia, Kostmann disease, Chediak-Higashi syndrome, hyper IgM syndromes, severe combined immunodeficiency, hyper IgE syndrome, and common variable immunodeficiency.

In order to determine the clinical and laboratory features of X-linked agammaglobulinemia, the records of 33 male patients with XLA were reviewed during 22 years (1980-2002) in the Iranian referral center of primary immunodeficiency disorders. The patients' ages ranged from 20 to 360 months (median 113 months). The median age at the onset of the disease was 8 months and the median age of diagnosis was 48 months, with a median diagnosis delay of 33 months. Almost all of the patients presented common infectious diseases, which were: pneumonia, otitis, diarrhea, sinusitis, and arthritis. During the course of illness, infections in the respiratory tract, gastrointestinal tract, central nervous system, and musculoskeletal system were seen in 93.9%, 75.8%, 33.3%, and 21.2% of XLA patients, respectively. The most common complications of these patients were chronic infections in 75.8% of them, including: chronic otitis media, chronic sinusitis, chronic diarrhea, and bronchiectasis.

Background: Chronic granulomatous disease (CGD) represents a group of inherited disorders of the phagocytic system, involving recurrent infections at different sites, especially the respiratory system. The present study was accomplished in order to determine the clinical spectrum of Iranian patients with CGD. Methods: Forty-one patients (29 males and 12 females) with CGD, who had already been referred to two immunodeficiency referral centers in Iran, were reviewed during a 22-year period (1980–2002). Results: These patients belonged to 34 families, and 56% of them were consanguineous. The median age at the time of study was 12 years (3 months to 22 years). The median age at onset of symptoms was 4 months (1 month to 12 years), and the median diagnostic age was 5.5 years (2 months to 20 years), with a diagnostic delay of 3 years on average. The most common presenting complaint in our CGD patients was lymphadenopathy (seen in 11 patients, 26.8%). The most common manifestations of CGD (in descending order) were lymphadenopathy (75.6%), pulmonary infections (65.9%) and skin involvement (63.4%) during their illness, followed by gastrointestinal (56.1%), skeletal (29.3%), upper respiratory tract (26.8%) and central nervous system (2.4%) involvement. Conclusions: Early diagnosis of the disease is crucial. In view of the possibility of timely treatment, i.e. prophylactic treatment of infection, CGD should be excluded in any patient with unexplained infections or granulomas.

Agammaglobulinemia is characterized by failure of B-cell differentiation (hypogammaglobulinemia) and increased susceptibility to bacterial infections. The present study was set up in order to evaluate the effectiveness of intravenous immunoglobulin (IVIG) treatment on the incidence of pneumonia in patients with agammaglobulinemia. We carried out chart reviews of 23 patients with agammaglobulinemia (mean age 11.5+/-5.4 years), who had been observed in a 22-year period (July 1981-January 2003) in Iran's referral center for primary immunodeficiency disorders. Nineteen of these 23 (82.5%) had been infected with pneumonia at least once before receiving the immunoglobulin treatment and 11 of them had experienced multiple episodes. During treatment with gamma-globulin - over a mean period of 6.8+/-4.1 years (range: 0.8-15.3 years) - the incidence of pneumonia requiring treatment or hospitalization decreased from 0.82 to 0.12 per patient per year (P=0.006). During IVIG replacement, hospitalization due to pneumonia decreased from 0.58 to 0.05 per patient per year (P=0.08) and the immunoglobulin G level (mean+/-S.D.) changed from 66.2+/-63.9 (range: 0-210 mg dl(-1)) to 552.4+/-199.1 (range: 136-942 mg dl(-1)) (P

Epidemiological studies have shown wide geographical and racial variation in the prevalence and patterns of immunodeficiency disorders. To determine the frequency of primary immunodeficiencies (PID) in Iran, the Iranian Primary Immunodeficiency Registry (IPIDR) was organized in 1999. We extracted the patient's data, by using a uniform questionnaire from their hospital records. The diagnosis of patients was based on WHO criteria. By now, 440 patients with PID, who were observed during a period of 20 years, have been registered in our registry. Among these patients, the following frequencies were found: predominantly antibody deficiency in 45.9% of patients (n = 202), phagocytic disorders in 29.09% (n = 128), T-cell disorders in 24.31% (n = 107), and complement deficiencies in 0.68% (n = 3). Common variable immunodeficiency was the most frequent disorder (n = 98), followed by chronic granulomatous disease (n = 86), ataxia telangiectasia (n = 48), x-linked agammaglobulinemia (n = 45), selective IgA deficiency (n = 42), combined immunodeficiency (n = 15), and severe combined immunodeficiency (n = 14). This study revealed that antibody deficiencies is the most frequently diagnosed primary immunodeficiency disorder in our patients, which is similar to that observed in other registries. A comparative study shows some differences between our results and other registries.

Asthma is one of the most common acute and chronic conditions in children, and the pediatricians are expected to provide an important role for asthma care in this age group, however there is no published information describing the different aspects of their practices about children asthma in Iran. This study was done to characterize the knowledge of the Iranian pediatricians about the diagnosis, treatment and education of asthma in children. Validated questionnaires were completed by 193 pediatricians from different parts of Iran during the International Congress of Pediatrics in Tehran. A total of 193 returned questionnaires (96.5%) were eligible for the survey and analysis. About 49% of the respondents were male and 18% were sub-specialists. Wheezing was the most common mentioned symptoms in taking asthma into consideration. About 40% of these physicians had no plan for doing spirometry in eligible children and 35.2% of them did not have familiarity with peak flowmeter. Also about 17.6% of them paid no regular visits to their asthmatic patients. Only 29% of the respondents indicated that they would prescribe inhaled corticosteroids for a 6-year-old child with moderate persistent asthma and 73.3% of them would prescribe inhaled bronchodilator (Salbutamol) for an acute asthmatic attack as the first drug, while 17.1% of them used epinephrine injection for this purpose. About 42.2% of the respondents did not consider any education or action plan for their patients and only 60.6% of them had access to standard guidelines and educational programs. The results show that there are numerous aspects of children asthma management in Iran which are not consistent with standardized guidelines and recommendations. This survey and the attained information suggest areas for interventions to improve the pediatricians' knowledge about asthma and the disease management.