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Purpose: Major histocompatibility complex class II (MHC-II) deficiency is a rare inborn error of immunity (IEI). Impaired antigen presentation to CD4+ T-cells results in combined immunodeficiency. Patients typically present with severe respiratory and gastrointestinal tract infections at early ages. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy. Methods: We describe the clinical, immunologic, and genetic features of eighteen unrelated Iranian patients with MHC-II deficiency. Results: Consanguinity was present in all affected families. The median age at the initial presentation was 5.5 months (range seven days to 18 years). The main symptoms included failure to thrive, persistent diarrhea, and pneumonia. Autoimmune and neurologic features were documented in 30% of the patients, respectively. Thirteen patients carried RFXANK gene mutations, two carried RFX5 gene mutations, and three carried a RFXAP gene mutation. Six patients shared the same RFXANK founder mutation (c.162delG); limited to the Iranian population and dated to approximately 1,296 years ago. Four of the patients underwent HSCT; three of them are alive. On the other hand, nine of the fourteen patients who did not undergo HSCT had a poor prognosis and died. Conclusion: MHC-II deficiency is not rare in Iran, with a high rate of consanguinity. It should be considered in the differential diagnosis of combined immunodeficiency (CID) at any age. With the limited access to HSCT and its variable results in MHC-II deficiency, implementing genetic counseling and family planning for the affected families are mandatory. We better determined the c.162delG RFXANKheterozygous mutation frequency in the Iranian population.

Background Diabetic ketoacidosis (DKA) is a serious complication of type 1 diabetes. A few studies have reported that COVID-19 is associated with the development of new-onset diabetes. Here, we present an infected child with new onset diabetes leading to DKA. Case presentation A 10-year-old patient with respiratory distress admitted to the Emergency Department of our center. The patient's COVID-19 Polymerase Chain Reaction (PCR) test was positive and also biochemical analyses confirmed that he had DKA. Despite standard initial treatments, ketoacidosis remained resistant; hence we prescribed oral bicarbonate (40 cc every 8 h) to treat the patient's refractory acidosis. Due to the patient's improvement, he was discharged after 10 days (7 days in the PICU), receiving outpatient enoxaparin (for a week) and ongoing subcutaneous insulin. Conclusion We report an interesting case of a child with COVID-19 infection precipitating presentation with new onset diabetes. Due to refractory acidosis, starting oral bicarbonate treatment after 2 days improved acidosis and tachypnea in the patient. The patient's medical team suggest close biochemical monitoring, prescribing enoxaparin for high level of D-dimer, and ordering oral bicarbonate acidosis persists.

Background: Gastroesophageal reflux disease (GERD) is one of common esophageal diseases in adolescents. Recent evidence has shown that dietary patterns might be associated with GERD risk. The aim of this study was to assess the association between a Mediterranean style diet (MedDiet) and GERD in a large sample of adolescents living in central Iran.Methods: This cross-sectional study conducted on 5141 adolescents aged between 13-14 years. Dietary intake assessed by using a food frequency method. The GERD diagnosed using a six-item questionnaire, which askes about its symptoms including heartburn, sense of reflux, poor sleep, medication use, nausea and epigastric pain. A binary logistic regression used to evaluate the relationship between the MedDiet score and GERD and its associated symptoms.Results: The analyses revealed that after adjustment for all possible confounding variables, the adolescents in the highest adherence to the MedDiet score had lower odds of GERD [odds ratio (OR)= 0.53; 95% CI 0.35-0.80, Ptrend = 0.005)], sense of reflux (OR= 0.45; 95 % CI 0.26-0.77, Ptrend = 0.01) and poor sleep (OR= 0.54; 95% CI 0.31-0.96, Ptrend = 0.02) compared with those in the lowest adherence. This association remained significant after adjustment for confounding factors including of age, sex, watching TV and computer and BMI. No significant link found between MedDiet and other GERD symptoms.Conclusion: The present study reported an inverse association between adherence to a Mediterranean style diet and GERD among Iranian adolescents. Adherence to MedDiet may be an important strategy in preventing GERD in adolescents.

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.

Dairy products may be linked to an increased risk of asthma, although there is little scientific evidence to back this up. The goal of this study was to look at the link between dairy consumption and asthma symptoms. This cross-sectional study was conducted on children and adolescents aged 6-8 and 13-14 living in central Iran. Dietary food consumption was assessed using a multiple-choice questionnaire. Logistic regression was used to obtain odds ratios for the association between milk, other dairy products, and total dairy consumption with asthma symptoms. In total, 7667 participants (3414 boys and 4253 girls) were included in the current study. Milk intake and total dairy consumption were not associated with the likelihood of wheezing, asthma confirmed by a doctor, current asthma, and asthma medication use. However, the analysis revealed that those who eat other dairy products on most days or every day might have a reduced likelihood of wheezing compared to those who do not eat or rarely eat other dairy products (OR: 0.65, 95% CI 0.44-0.94, Pterend=0.18). After adjusting for age, sex (OR: 0.58, 95% CI 0.39-0.84, Pterend=0.03), and additionally adjusting for watching TV and computer use (OR=0.58, 0.40-0.85, Pterend=0.02), and BMI (OR: 0.58, 95% CI 0.40-0.85, Pterend=0.02), individuals in the highest category of other dairy consumption had significantly lower odds of wheezing compared with those with the lowest intakes. In conclusion, the consumption of dairy products other than milk, including cheese and yogurt, might reduce the likelihood of wheezing in children and adolescents.

Protein kinase C is a family of serine/threonine kinases that play a key role in the adaptive immune cell signaling, as well as regulation of growth, apoptosis, and differentiation of a variety of cell types. Patients homozygous for a null mutation of the Protein Kinase C DeltaThe data were collected by direct interview and examining the patient's clinical record. Whole-exome sequencing was performed to detect the underlying genetic mutation in the patient. We also conducted electronic searches for ALPS-like reported patients in PubMed, Web of Science, and Scopus databases.In this study, we reported a 13-year-old boy who presented with autoimmunity, lymphoproliferation, recurrent pneumonia, cardiomyopathy, and dermatological manifestations. An elevation of double-negative T cells, CD8PRKCD should be considered in the context of ALPS clinical manifestations with prominent dermatological involvements.

Asthma, as the most common chronic disease in children, encompasses substantial health and socioeconomic burden worldwide. This study aimed to evaluate the prevalence, severity, and management of asthma in adolescents aged 13-14 years. This cross-sectional study, which was part of the Global Asthma Network (GAN) 2020 survey, was conducted in early 2020 in Yazd, Iran. A total of 48 schools in Yazd city were selected by cluster sampling. In this study, 5141 students, including 3069 (59.7%) females and 2072 (40.3%) males participated. Prevalence of ever and current wheezing was 19% and 9% respectively. The former was significantly higher in males than females (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.

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.

Phenobarbital is still one of the most commonly used medical treatments for different types of seizures. It has numerous different side-effects. Antiepileptic hypersensitivity syndrome (AHS) is a rare and potentially life-threatening adverse reaction to aromatic anticonvulsants such as phenobarbital. Its characteristic features are fever, rash, and lymphadenopathy with different severity of hematologic abnormalities. This case report presents a 26-month-old girl that developed fever, disseminated maculopapular rash, petechiae and thrombocytopenia two weeks after the initiation of phenobarbital prescribed for febrile seizure prophylaxis. The patient was admitted in our center with the impression of hypersensitivity syndrome, so phenobarbital was discontinued and her treatment was resumed with methylprednisolone and intravenous immunoglobulin. After a few days, all symptoms improved and the platelet count was normalized. Thrombocytopenia is a rare complication of hypersensitivity syndrome to phenobarbital in children. Paying attention to this point can prevent the life-threatening adverse effects of this highly consumed medicine.

Defects in interleukin-10 (IL10) and interleukin-10 receptors (IL10R) are closely related to very early onset (infantile) inflammatory bowel disease (VEO-IBD). In the present study, we report a novel homozygous null mutation within interleukin-10 receptor B (IL10RB) gene in a child presenting with severe VEO-IBD. In accordance with previous reports, our patient manifested with chronic diarrhea, failure to thrive, intermittent fever and multiple anal ulcers associated with Candidiasis. Homozygous null mutation within IL10RB gene (c.92C > T, p.S31P) affecting the extracellular domain of protein was discovered in this patient. In conclusion, the diagnosis of IL-10R gene mutations should always be considered as a possible cause of refractory diarrhea and failure to thrive. Mutation analysis could help detect the genetic defects associated with these clinical manifestations and to determine the most appropriate treatment option for patients affected by this disease.

Background. Primary immunodeficiency diseases (PIDs) are life-threatening disorders, which manifest commonly with gastrointestinal (GI) signs, mainly as chronic diarrhea. Objective. To investigate and compare infectious etiology of chronic diarrhea in different PIDs. Patients and methods. Assessing clinical features, obtaining immunological profiles, as well as characterizing infectious etiology of diarrhea were performed in 38 PID patients with chronic diarrhea. Stool samples and/or biopsy specimens were checked using culture, microscopic examination, RT-PCR, and PCR, as appropriate. The patients were diagnosed to have common variable immunodeficiency (CVID), severe combined immunodeficiency (SCID), X-linked agammaglobulinemia (XLA), and hyper-IgM (HIgM) syndrome. Results. In 32 patients we identified 41 infectious agents including 16 parasitic (39.0, the most common Giardia lamblia), 11 bacterial (26.8, the most common salmonella spp), 8 viral (19.5, the most frequent group A rotavirus), and 6 fungal organisms (14.7, the most common Candida albicans). From 6 of the patients, no infectious agent was isolated. In CVID bacteria and parasites, in SCID bacteria and viruses, in XLA parasites, and in individuals with HIgM syndrome parasites were the leading causes of chronic diarrhea. Infection with giardia and cryptosporidium were more frequent in XLA and HIgM, respectively. Conclusion. The current study suggests considering both usual and unusual pathogens in laboratory investigation and in the empiric treatment of chronic diarrhea. Opportunistic pathogens should be taken into account when no other pathogen is identified, especially in patients on long-term treatment or prophylaxis with antifungals/antibiotics and in those from geographical locations that favor pathogenicity of these organisms. © 2019, EDRA S.p.A. All rights reserved.

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.

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.

Common variable immunodeficiency (CVID) is a heterogeneous group of disorders with varied immunologic phenotypes and clinical manifestations. Patients with CVID are mainly characterized by decreased serum immunoglobulin levels, and increased susceptibility to recurrent bacterial infections, autoimmune disorders, and malignancies. Here we present a CVID patient who has developed a clinical polyclonal lymphocytic infiltration phenotype associated with severe and irreversible pancytopenia with unknown etiology. Progressive unilateral loss of vision and cytomegalovirus retinitis indicated the cause of patient's pancytopenia.

Central venous pressure (CVP) measurement is a reliable method for evaluating intravascular volume status and cardiac function, but it is an invasive method that results in some complications such as arterial puncture, pneumothorax, and development of infection. The current study was performed to compare CVP measurements between central and peripheral catheters in infants and children with congenital heart disease referred for right-sided heart catheterization. The CVP and peripheral venous pressure (PVP) in 45 patients were measured simultaneously. The mean difference between CVPs measured from the central and peripheral catheters was 8 +/- 4 cm H(2)O. The linear regression equation showed that CVP = 0.32 PVP + 3.8 (r = 0.67; p0.005). There was no difference in CVP measurements depending on the intravenous cannula and chest diameters, arm diameter, arm length, body surface area, patient's age (or =10 years and10 years), and type of congenital heart disease (cyanotic or noncyanotic). In conclusion, although CVP measured from a peripheral intravenous catheter in infants and children with congenital heart disease is not as accurate as the measurement in adults, the aforementioned linear regression equation based on measurement of PVP gives a reliable estimate of CVP.

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.

Rheumatoid arthritis is a systemic, chronic inflammatory autoimmune disease affecting many tissues but principally attacking the joints. Auto antibodies such as rheumatoid factor and anti-cyclic Citrullinated peptide antibodies have important diagnostic value. This cross-sectional analytical study was performed at a single medical institution in central Iran (Shahid Sadoughi Hospital, Yazd, Iran) in order to compare the diagnostic value of anti-cyclic citrullinated peptide antibodies and rheumatoid factor in patients with rheumatoid arthritis. Serum levels of anti-cyclic citrullinated peptide antibodies were determined by enzyme-linked immunosorbent assay, and levels of rheumatoid factor were determined by turbidimetry on a latex-enhanced agglutination assay in 266 patients with rheumatoid arthritis and 134 patients with non-rheumatoid arthritis rheumatic diseases. Among the 266 patients with rheumatoid arthritis, 188 patients (70.7%) were tested positive for anti-cyclic citrullinated peptide antibodies, and 123 patients (46.2%) were tested positive for rheumatoid factor. The sensitivity, specificity, positive predictive value and negative predictive value of anti-cyclic citrullinated peptide antibodies for diagnosing rheumatoid arthritis were 70.76%, 85.07%, 90%, and 59% respectively. Those for rheumatoid factor were 46.26%, 90.29%, 90%, and 45% respectively. The anti-cyclic Citrullinated peptide antibodies measurement is a useful test for diagnosing rheumatoid arthritis. Due to its high positive predictive value and negative predictive value, it is an important diagnostic test and gives accurate diagnosis of the disease. However, this does not mean that anti-cyclic citrullinated peptide antibodies can replace rheumatoid factor in the diagnosis of rheumatoid arthritis, because not all rheumatoid arthritis patients have anti-cyclic Citrullinated peptide antibodies. The two tests therefore appear to be complementary.

Background Allergic rhinitis (AR) is an inflammatory disorder of the upper airway. T-helper (Th)2 cytokines seems to have major roles behind the scene of unpleasant symptoms resulted from AR. Expression of interleukin (IL)-4 and its receptor could be affected by single nucleotide polymorphisms (SNPs). This study assessed the effect of 4 genetic variants within genes of IL-4 and IL-4R in AR. Methods Allele frequencies of one IL-4R variant (rs1801275) and three SNPs of IL-4 (rs2243248, rs2243250, and rs2070874) were investigated in 98 patients with AR, compared to a group of controls, using PCR sequence-specific-primers (PCR-SSP) method. Results Homozygosity for the C allele of rs2243250 in IL-4 was significantly overrepresented in the patient group. CC genotype in rs2070874 significantly was correlated with AR. GG/CC/CC and TT/TT/TT (rs2243248, rs2243250, and rs2070874) haplotypes in the IL-4 gene had a significant negative correlation with AR. Conclusion SNPs in IL-4 are associated with AR and could change the clinical picture of the disease in patients.

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

Although autoimmunity phenotype is surprisingly common in patients with different types of primary antibody deficiency, it is much less frequent in X-linked agammaglobulinemia (XLA). Herein, we report on a 15-month-old boy with XLA who also suffered from Kawasaki disease. The current case presentation is the first report of an association between Kawasaki disease and XLA. XLA could be considered as a special opportunity to understand autoimmunity in the near absence of immunoglobulins.

RATIONALE - Interleukin-4 (IL-4) has pivotal role in promotion of T helper2 responses. ll-4 is also an important regulator of adaptive immune responses. This study is aimed at investigating of association of polymorphisms in IL-4 and IL-4-receptor genes with susceptibility to CIU. METHODS - A matched case-control study was conducted on 89 patients with CIU and 138 healthy controls. Autologous serum skin test (ASST) was performed according to international standards. Total IgE levels, thyroid peroxidase antibodies (TPO) and anti thyroglobulin antibodies (ATG) were investigated using spectrophotometry and enzyme-linked immunosorbant-assay, respectively. Single nucleotide polymorphisms at following positions were genotyped using polymerase chain reaction: IL-4-1098T>G (rs243248), -590C>T (rs2243250), -33C>T (rs2070874), and IL-4-receptor+1902A>G (rs1801275). Estimated frequencies were compared between patients and controls. RESULTS - ASSTwas positive in 39 (43.8%) and abnormal TPO and ATG were found in 12 (13.4%) and 6 (6.7%) of patients which were significantly higher than controls (pT (OR 2.39, 95%CI (1.41 to 4.05), p T (OR 4.5, 95%CI (1.9 to 10.82)) and -33C>T (OR 3.46, 95%CI (1.88 to 6.43)), were significantly higher in CIU patients (p

Atopic dermatitis (AD) is a chronic skin disorder of unknown origin that usually manifests for the first time in early infancy. Different types of genetic predisposition and environmental factors seem to be associated with the disease.This study was performed to evaluate the frequency of alleles, genotypes, and haplotypes of interleukin (IL) 6 single-nucleotide polymorphisms (SNPs) at positions -174 and nt565 in 89 Iranian children with AD and 139 healthy controls.The G allele was significantly more frequent at position -174 in IL6 in atopic patients than in the healthy controls (P.001; OR, 2.82). Genotype GG was found at the same position in 71% of the patients; this frequency was significantly higher than the frequency of 30% recorded in the controls (P.001; OR, 5.60). The GG haplotype of IL6 (-174, nt565) was significantly more frequent in the atopic patients than in the healthy controls (P.001; OR, 2.99).A significant increase in the frequency of the G allele and GG genotype at position -174 of IL6 was found in patients with AD, thus suggesting that production of this cytokine is greater in atopic patients.