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Background: Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disease caused by mutations in the ADA2 gene. DADA2 has a broad spectrum of clinical presentations. Apart from systemic manifestations, we can categorize most of the signs and symptoms of DADA2 into the three groups of vasculitis, hematologic abnormalities, and immunologic dysregulations. The most dominant vasculitis features are skin manifestations, mostly in the form of livedo racemosa/reticularis, and early onset ischemic or hemorrhagic strokes. Hypogammaglobulinemia that is found in many cases of DADA2 brings immunodeficiencies into the differential diagnosis. Cytopenia, pure red cell aplasia (PRCA), and bone marrow failure (BMF) are the hematologic abnormalities commonly found in DADA. Case presentation: We introduce eleven patients with DADA2 diagnosis, including two brothers and sisters, one set of twin sisters, and one father and his daughter and son. Ten patients (91%) had consanguineous parents. All the patients manifested livedo racemose/reticularis. Ten patients (91%) reported febrile episodes, and seven (64%) had experienced strokes. Only one patient had hypertension. Two of the patients (11%) presented decreased immunoglobulin levels. One of the patients presented with PRCA. Except for the PRCA patient with G321E mutation, all of our patients delivered G47R mutation, the most common mutation in DADA2 patients. Except for one patient who unfortunately passed away before the diagnosis was made and proper treatment was initiated, the other patients' symptoms are currently controlled; two of the patients presented with mild symptoms and are now being treated with colchicine, and the eight others responded well to anti-TNFs. The PRCA patient still suffers from hematologic abnormalities and is a candidate for a bone marrow transplant. Conclusions: Considering the manifestations and the differential diagnoses, DADA2 is not merely a rheumatologic disease, and introducing this disease to hematologists, neurologists, and immunologists is mandatory to initiate prompt and proper treatment. The efficacy of anti-TNFs in resolving the symptoms of DADA2 patients have been proven, but not for those with hematologic manifestations. Similarly, they were effective in controlling the symptoms of our cohort of patients, except for the one patient with cytopenia. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the maternal and umbilical cord blood antibody levels, after COVID vaccination during pregnancy. Method: The women who received the COVID‐19 vaccine (Sinopharm) during pregnancy were included. Maternal and cord blood samples were tested to detect the severe acute respiratory syndrome coronavirus 2 receptor binding domain (RBD) specific antibodies. In addition, obstetric information and side effects after vaccination were gathered. Result: A total of 23 women were included. Eleven pregnant women took two doses and 12 cases received a single dose of the vaccine. No IgM antibody was detected in any maternal blood or cord blood samples. The RBD‐specific Immunoglobulin G (IgG) antibody was positive in mothers receiving 2 doses of the vaccine and their infants. But the antibody titers were under the positive cut‐off threshold for the other 12 women who were vaccinated with a single dose. Women who received both doses of vaccine had significantly higher IgG levels than a single dose of Sinopharm (p =.025). The same result was demonstrated in infants born to these mothers (p =.019). Conclusion: There was a significant correlation between maternal and neonatal IgG concentrations. Although, receiving both doses of the BBIBP‐CorV vaccine (not 1 dose) during pregnancy is highly beneficial for increasing humoral immunity for the mother and fetus. [ABSTRACT FROM AUTHOR]

Neutropenia congenita grave (SCN) is a rare disease with a genetically and clinically heterogeneous nature, usually diagnosed in childhood, with an elevated risk of infections such as otitis, skin infections, pneumonia, deep abscesses, and septicemia. Patients with SCN also have an increased risk of leukemia, and mutations in the ELANE and the HAX1 genes have been observed in those patients. This study was conducted to genetically screen six Iranian families with SCN who have at least one affected person. In the first step, all exons and intron boundaries of ELANE and HAX1 genes were sequenced in probands. Cases with no pathogenic mutations were tested through whole-exome sequencing (WES). Analysis showed five different variants in ELANE (c.377 C>T), HAX1 (c.130_131 insA), HYOU1 (c.69 G>C and c.2744 G>A) and SHOC2 (c.4 A>G) genes in four families. We found that two out of six families had mutations in ELANE and HAX1 genes. Moreover, we found two novel mutations at the HYOU1 gene that had not previously been reported, as well as a pathogenic mutation at SHOC2 with multiple phenotypes, that will contribute to determining the genetic basis for SCN. Our study revealed that WES could help diagnose SCN, improve the classification of neutropenia, and rule out other immunodeficiencies such as autoimmune neutropenia, primary immunodeficiency diseases, and inherited bone marrow failure syndromes. [ABSTRACT FROM AUTHOR]

Context: Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 can involve multiple organs, especially the heart, in some children with prior COVID-19 infection. The World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) guidelines provide valuable case definitions for MIS-C, as utilized in this study. We aimed to identify and summarize the echocardiographic findings of MIS-C based on these case definitions. Evidence Acquisition: We performed a systematic search in PubMed, Embase, Scopus, and Cochrane databases. An additional source was also utilized to extend the identified records. The articles underwent a two-step screening process. Then, eligible articles were included in the qualitative synthesis. Results: We identified 33 eligible studies, recruitingl,392 patients with MIS-C. Male patients were the majority, with 791 (56.8%) cases. The mean age of the patients was 8.3 ± 5.9 years, while 28.5% of the children were identified with underlying conditions. The most common echocardiographic findings were left ventricular systolic dysfunction (34.91%), valvular regurgitation (29.08%), pericardial involvement (22.58%), and coronary abnormalities (18.0%). Conclusions: MIS-C is a rare complication of COVID-19 in children. Early cardiologic investigations, especially echocardiography, can reveal manifestations, including myocardial dysfunction, coronary abnormalities, valvularpathologies, and pericardial involvement. [ABSTRACT FROM AUTHOR]

A growing body of evidence from the United Kingdom (UK), Europe, and the United States of America (USA) suggests that a number of paediatric patients could present with Kawasaki-like symptoms such as fever, rash and shock with concomitant COVID-19 infection which has been referred to multisystem inflammatory syndrome in children (MIS-C). With respect to her history of contact with COVID-19, preceding upper respiratory tract symptoms, positive IgG for SARS-CoV-2 and negative blood culture; our patient's symptoms appear to be related to COVID-19. Hyperinflammatory shock related to COVID-19 in a patient presenting with multisystem inflammatory syndrome in children: First case from Iran. [Extracted from the article]

Griscelli syndrome (GS) is a rare autosomal recessive disease that affects hair, skin, and immune system. Here, we describe an 8.5-month-old infant with multiple admissions due to fever, petechial purpura, and several recurrent vomiting episodes with a presumptive diagnosis of recurrent sepsis. He was born from parents with consanguineous marriage. The initial examinations revealed huge splenomegaly and hepatomegaly without any source of infection. Laboratory tests revealed a hemophagocytic lymphohistiocytosis (HLH) like a picture with a high blood level of ferritin in all episodes, but the bone marrow test result was normal. Although he had normal hair and skin pigmentation on physical examination, the accumulation of melanosomes was found in his hair shafts on microscopic investigations. Eventually, a genetic test revealed a mutation in the RAB27A gene, which confirmed GS-II diagnosis. Our case is the first case of GS-II from Iran without any apparent clinical features of GS, such as hypopigmented skin and silvery-gray hair. Therefore, a genetic test, together with the microscopic examination of hair and skin, is necessary for the diagnosis and confirmation of GS-II. Since GS-II is an autosomal recessive disorder and consanguineous marriages are popular in Iran, premarital genetic counseling is recommended for this region. [ABSTRACT FROM AUTHOR]

There is strong evidence on the interaction of several genetic variations and environmental conditions in the etiology of asthma. Association of a disintegrin and metalloproteinase 33 (ADAM33) with asthma risk is not clear and shows diversity between nations and ethnicities. Several single nucleotide polymorphisms (SNP) of the ADAM33 gene are introduced and studied according to the disease onset and characteristics. The aim of our study is to determine the association of ADAM33 rs2280091 polymorphism and pediatric asthma in the Iranian population. A total of 63 asthma patients (aged 6-18) and 86 healthy controls were enrolled in our study. Asthma type, classification, and severity were defined. SNPs of the ADAM33 gene at rs2280091 (T1) were analyzed. Pulmonary function tests, total blood eosinophil count, and IgE count were also assessed. T1 genotype and allele frequencies were not associated with asthma risk in Iranian pediatric asthma. Atopic asthma subgroup and patients with normal eosinophil count showed association with ADAM33 rs2280091. Moreover, asthma patients with AG genotype showed lower pulmonary functions. [ABSTRACT FROM AUTHOR]

Objectives: Protein tyrosine phosphatase non-receptor type 22 gene (PTPN22) single-nucleotide polymorphisms (SNP) have been associated with a number of different autoimmune diseases. This study aimed to investigate the association of five polymorphisms of PTPN22 gene with susceptibility to ulcerative colitis (UC) in Iran. Materials and methods: A total of 67 patients diagnosed with UC (35 female and 32 male all under 18 years) and 93 healthy subjects were selected. The samples were genotyped for the, rs12760457, rs2476601, rs1310182, rs1217414, and rs33996649 in PTPN22 gene using real-time polymerase chain reaction (PCR) allelic discrimination TaqMan genotyping assays. Results: The frequencies of the rs1310182 A and G alleles, and also the AA and GG genotypes were significantly different between the patient and the control groups (p < 0.05). The carriage of G allele of rs1310182 was significantly associated with increased risk of UC (OR (95% CI) = 1.17 (0.70–1.98), p < 0.001). Moreover, the genotype GG of SNP rs1310182 was significantly associated with UC (OR (95% CI) = 2.32 (1.13–4.76), p < 0.01). No association was found between other PTPN22 gene SNPs among UC patients. Conclusion: PTPN22 gene polymorphism in rs1310182 could play a crucial role in susceptibility to UC. [ABSTRACT FROM AUTHOR]

Objectives: Ataxia-telangiectasia (A-T) is an autosomal recessive multisystem disorder characterised by cerebellar degeneration, telangiectasia, radiation sensitivity, immunodeficiency, oxidative stress and cancer susceptibility. Epidemiological research has shown that carriers of the heterozygous ataxia-telangiectasia mutated (ATM) gene mutation are radiosensitive to ionising irradiation and have a higher risk of cancers, type 2 diabetes and atherosclerosis. However, there is currently no fast and reliable laboratory-based method to detect heterozygous ATM carriers for family screening and planning purposes. This study therefore aimed to evaluate the ability of a modified G2-assay to identify heterozygous ATM carriers in the families of A-T patients. Methods: This study took place at the Tehran University of Medical Sciences, Tehran, Iran, between February and December 2017 and included 16 A-T patients, their parents (obligate heterozygotes) and 30 healthy controls. All of the subjects underwent individual radiosensitivity (IRS) assessment using a modified caffeine-treated G2-assay with G2-checkpoint abrogation. Results: The mean IRS of the obligate ATM heterozygotes was significantly higher than the healthy controls (55.13% ± 5.84% versus 39.03% ± 6.95%; P <0.001), but significantly lower than the A-T patients (55.13% ± 5.84% versus 87.39% ± 8.29%; P = 0.001). A receiver operating characteristic (ROC) curve analysis of the G2-assay values indicated high sensitivity and specificity, with an area under the ROC curve of 0.97 (95% confidence interval: 0.95–1.00). Conclusion: The modified G2-assay demonstrated adequate precision and relatively high sensitivity and specificity in detecting heterozygous ATM carriers. [ABSTRACT FROM AUTHOR]

The ATP8A2 protein is mainly located in the brain and takes part in the lipid flipping process. Mutations in the ATP8A2 gene and chromosomal translocations that interfere with the ATP8A2 gene product have been reported in association with global developmental delay and hypotonia. Here, we will report a threeyear- old male presented with major phenotypic features of dysequilibrium syndrome (DES), including severe hypotonia, global developmental delay, speech problem, and strabismus. Whole exome sequencing revealed a homozygous in-frame deletion in the ATP8A2 gene (c.1286_1288delAGA, p.Lys429del). This ATP8A2 variant has not been reported yet and seems to be linked to the phenotypic features of dysequilibrium syndrome. [ABSTRACT FROM AUTHOR]

Neutropenia is characterized by a decrease in circulating neutrophil counts and consequent infections. The present study was performed to describe the clinical and laboratory findings of patients with congenital neutropenia in northwestern Iran. Medical records of 31 patients with congenital neutropenia out of 280 neutropenic patients who had been referred to Tabriz Children's Hospital during a 3-year-period (2011- 2014), were reviewed. Thirty-one cases (17 female and 14 male), with a mean age of 46.21±37.92 months, were diagnosed to suffer from congenital neutropenia. The disorders associated with congenital neutropenia were combined immunodeficiency (8 cases), severe congenital neutropenia (6 cases), common variable immunodeficiency (4 cases), severe combined immunodeficiency (2 cases), and metabolic syndrome (1 case). The median age of the onset of disease was 13.16±12.48 months. The most common clinical manifestations during the course of illness were otitis media (13 cases), pneumonia (12 cases), recurrent aphthous stomatitis, lymphadenopathy, and gingivitis (11 cases). Four neutropenic patients died because of recurrent infections. Neutropenia may occur in the context of the primary immunodeficiency disorders. Unusual, persistent or severe infections always pose a speculation to search for an underlying immunodeficiency syndrome and neutropenia, so as to avoid further life-threatening complications as a result of any delay in diagnosis. [ABSTRACT FROM AUTHOR]

Chronic heart failure (CHF) is a complex clinical syndrome that represents the end stage of various cardiac diseases and is characterized by the inability of the heart to meet metabolic demands of the body. Many physiological systems are involved in this disease. In particular, the activation of the immune system has received considerable interest in the last decade. Evidence from both experimental and clinical trials indicates that inflammatory mediators are of importance in the pathogenesis and progression of chronic heart failure. Excessive pro-inflammatory cytokines induce contractile dysfunction, hypertrophy, and fibrosis and cell death in Cardiac myocyte. We examined the expression of IL-23 in PBMCs between CHF patients and healthy controls. In this report, we used real-time PCR assay to compare the relative expression of IL-23 in peripheral blood mononuclear cells (PBMC) from CHF patients with various heart diseases (n=42, EF<45%, range of New York Heart Association (NYHA) 1 to 4) and matched healthy control subjects (n=42).We also determined the IL-23 concentrations of cell culture supernatant of PBMCs with ELISA. A total of 42 patients with CHF, with 42 age and sex-matched control group subjects were enrolled in the present study. The culture supernatant levels of IL-23 in PBMC of CHF patients were significantly higher (133.95±108.99 pg/mL) than in the control group (83.43±76.2 pg/mL) (P<0.05). The gene expression of IL-23 was also markedly upregulated in PBMC from CHF patients in comparison with the control group, but it was not statically significant 80. These results demonstrate that in patients with CHF and especially those with severe CHF, expression of pro-inflammatory cytokines and levels of IL-23 cytokine is markedly increased in PBMC. These finding suggested that IL-23 may play an important role in the progression of CHF among these patients. [ABSTRACT FROM AUTHOR]

There are controversies on the association of childhood allergic diseases with inflammatory bowel diseases (IBD). The aim of this study was to examine the association between food allergy, cow's milk allergy (CMA), and asthma with pediatric IBD in Iranian population. This case-control study was conducted on 200 individuals less than 18-year-old (100 with IBD and 100 as control group). Medical records, clinical presentation, and laboratory and para-clinical findings related to food allergy, CMA, and asthma were reviewed for all participants in both groups and were recorded. Among 100 children with IBD, 40 had Crohn's disease, and 60 had ulcerative colitis. The frequency of food allergy, cow's milk allergy, and asthma in children with IBD was significantly higher than the control group (P<0.001). Asthma in children with Crohn's disease was significantly more prevalent than children with ulcerative colitis (P=0.008). Food allergy (OR: 22.1, 95% CI: 5.1-95.05, P<0.001), CMA (OR: 15, 95% CI: 3-67, P<0.001), and asthma (OR: 10, 95% CI: 3-37.05, P<0.001) were significantly associated with increased risk of IBD in children. Food allergy, CMA in infancy and asthma are more prevalent in children with different subtypes of IBD. The diagnosis of these risk factors is associated with increased risk of Crohn's disease and ulcerative colitis. [ABSTRACT FROM AUTHOR]

Introduction: Juvenile-onset systemic lupus erythematosus is a multigenic autoimmune disorder. Polymorphisms ofMECP2gene have been reported to increase the risk of adult-onset SLE. In this study, we aimed to analyze ifMECP2gene polymorphisms could impress the proneness to JSLE in Iranian population.Material and Methods: Polymorphisms ofMECP2gene were genotyped in 50 Iranian JSLE patients and 426 matched healthy controls employing the real-time PCR allelic discrimination technique.Results: None of the alleles and genotypes ofMECP2gene SNPs had significantly different distribution between patients and controls. The CTAT haplotype was represented more frequently and significantly in JSLE cases than in controls. A strong linkage disequilibrium was observed among the variants.Conclusions: Although adult-onset SLE had been associated withMECP2gene variants, this gene is not associated with disease susceptibility in JSLE patients, implying the involvement of different susceptibility genes in the pathogenesis of SLE and JSLE. [ABSTRACT FROM PUBLISHER]

Juvenile idiopathic arthritis (JIA) is a clinically heterogeneous cluster of complex diseases, in which both the genetic and environmental factors seem to play a role in the development of the disease. The current study aims to assess the association of programmed cell death 1 (PDCD1, also called PD-1) gene variants with JIA vulnerability in Iranian population. In this case-control association study, we investigated a group of 50 Iranian patients with JIA in comparison with 202 healthy controls and evaluated the frequency of alleles, genotypes, and haplotypes of PDCD1 single-nucleotide polymorphisms (SNPs), comprising PD-1.1 G/A, PD-1.3 G/A and PD-1.9 C/T, using PCR-RFLP method. Both the allelic and genotype frequencies of PD-1.1, PD-1.3 and PD-1.9 were similar in two groups of patients and controls. Moreover, no significant difference was observed between the two groups of patients and controls for GGC (PD-1.1 G, PD-1.3 G, PD-1.9 C), GAC (PD-1.1 G, PD-1.3 A, PD-1.9 C), and AGT (PD-1.1 A, PD-1.3 G, PD-1.9 T) haplotypes. Our results did not show any association between PDCD1 SNPs and the development of JIA in Iranian population. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin (Ig) replacement therapy is used for treating a variety of primary immunodeficiency diseases (PIDs). Ig replacement therapy is the most important therapy for these diseases, since it protects the body against infections and reduces autoimmune disease symptoms. The purpose of this research was to estimate the cost of subcutaneous and intravenous Ig therapy in Iran. Methods: This study is carried out from the perspective of Iran’s healthcare system and all the medical costs are calculated. Cost variables include personnel, equipment, and supplies. The data required for cost estimation are obtained from the records of children’s Medical center of Tehran for 2015. Personnel and medical treatment costs are calculated based on relative value units. For SCIg, cost items are extracted from the literature. Results: The total cost of IVIg and SCIg for the health system in the first year of treatment is $1370 and $121 respectively. The results indicate that SCIg reduces costs and is the preferred treatment for PID patients. Conclusions: SCIg therapy significantly reduces the costs of the healthcare system compared to IVIg therapy, and this is enough economic justification for introduction of this treatment in the Iranian healthcare system. SCIg is also critical in reducing the direct costs of patients. [ABSTRACT FROM AUTHOR]

In orders to promote the level of healthcare in societies, governments try to have different policies to transform the health system. The aim of this study was to measure the level of awareness of practitioners in Iran, after initiating the new transformation of the health system in the country, starting from May 2014. This is a descriptive-cross-sectional study, which was inducted in October 2014. The study population consists of 208 physicians who attended the 26th International Congress of Pediatrics in Tehran, Iran. Data was collected using a self-structured questionnaire, which was estimated as both reliable and valid. Two hundred and eight questionnaires were returned. The results showed that 79.1% of the practitioners were aware of the new health system. Indeed 48.3% of the participants believed that the system was successful. 57.7% of physicians were completely aware of the time of the new system settlement in the country, while the rest had either no idea or did not know the exact date. The participants suggested a few items promote the health system in the country; among them, decreasing the direct payment between patients and physicians was suggested most frequently. According to the results obtained from the study, it is suggested that health care administrators have a detailed plan for health care workers prior to settlement of a new health policy installment, in order to succeed in settlement of a program. [ABSTRACT FROM AUTHOR]

Widespread use of oral poliovirus vaccine has led to an ≈99.9% decrease in global incidence of poliomyelitis (from ≈350,000 cases in 1988 to 74 cases in 2015) and eradication of wild-type poliovirus serotypes 2 and 3. However, patients with primary immunodeficiency might shed vaccine-derived polioviruses (VDPVs) for an extended period, which could pose a major threat to polio eradication programs. Since 1995, sixteen VDPV populations have been isolated from 14 patients with immunodeficiency in Iran. For these patients, vaccine-associated paralysis, mostly in >1 extremity, was the first manifestation of primary immunodeficiency. Seven patients with humoral immunodeficiency cleared VDPV infection more frequently than did 6 patients with combined immunodeficiencies. Our results raise questions about manifestations of VDPVs in immunodeficient patients and the role of cellular immunity against enterovirus infections. On the basis of an association between VDPVs and immunodeficiency, we advocate screening of patients with primary immunodeficiency for shedding of polioviruses. [ABSTRACT FROM AUTHOR]

Food allergy is a common disorder especially in the first years of life. Strict avoidance of the responsible food is the most effective therapeutic measure so far. But this continuous vigilance could be stressful for the patient and family and decreases their quality of life (QOL). This survey was designed to evaluate the impact of IgE-mediated food allergy on parental QOL in Iranian patients and to develop a valid Persian version of "Food Allergy Quality Of Life- Parental Burden (FAQL-PB) questionnaire". 90 patients (28 females, 62 males) and their parents who were referred to the clinic of Allergy in Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran were enrolled. The questionnaire was translated with scientific method and its reliability was approved in a pilot study (ICC=0.75, cronbach-α=0.90). Among all patients the most common allergens were wheat (60%) and cow's milk (42%). The patient's age (p=0.02), parent's gender (p=0.004), mother's age (p=0.02), duration of the disease (p=0.048), and allergen multiplicity (p=0.004) were found to have the most significant correlation with family and social activity (FSA) domain. The most meaningful associations were achieved between parent's gender (p<0.001) and emotional issues (EM); as well as meal preparation (MP) with patient's age (p=0.02), parent's gender (p<0.0001) and also allergen multiplicity (p= 0.003); likewise nutrition and health concern (NH) domain with parent's gender (p<0.001). Anaphylaxis's history did not place any burden on each domain. It was concluded that presence of food allergic patients in families could considerably affect all domains of QOL. [ABSTRACT FROM AUTHOR]

Background: Autoimmune hepatitis (AIH) is a chronic long-lasting hepatocellular inflammation associated with circulating auto antibodies. In addition to the genetic component, several cytokines have been implicated to be involved in AIH. This study was performed to investigate potential associations of AIH with IL4 gene variants. Method: The studied alleles and genotypes included: IL4G/T allele polymorphisms at position -1098 and C/T allele polymorphisms at two positions (-33 and -590) on the IL4 gene, in addition to the A/G allele polymorphisms at position +1902 on the IL4RA gene. Result: The IL4 C allele and CC genotype at position -590 and TT genotype at position -33 had a significantly higher frequency in AIH patients. Conclusion: This study identified the IL4 C allele and CC genotype susceptibility gene in AIH, which will provide better insights into the mechanisms of AIH and potential therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: Recurrent aphthous stomatitis (RAS) is a common disorder with an unclear etiopathogenesis. Involvement of the immune system in the development of this condition is strongly suggested. As the variations in the inflammasome-related NLRP3 gene have been suggested to affect immune system activity, this case-control study was performed to determine whether these genetic variants are associated with RAS. Methods: We studied a group of 69 Iranian patients with RAS in comparison with 56 healthy controls. We determined four single nucleotide polymorphisms (SNPs) of NLRP3 and performed association analyses of NLRP3. Genotyping was conducted using the TaqMan method. Results: The NLRP3 rs3806265 T allele was significantly more frequent in the patients with RAS than in the healthy controls (P = 0.003). While a significant negative association was found between the C allele at the same position with RAS (P = 0.003), the TT genotype was significantly more frequent at position rs3806265 in NLRP3 in patient group than in the controls (P = 0.002). However, the frequency of CT genotype at the same position was significantly higher in healthy controls than in the case category (P = 0.002). Conclusions: Considering the high frequency of the presence of NLRP3 rs3806265 TT genotype in patients with RAS, it seems that this gene polymorphism could affect individual susceptibility to RAS. [ABSTRACT FROM AUTHOR]

Seizures are among the most common causes of apparent life-threatening events. There are discrepancies among the published reports on the correlation between epilepsy/febrile seizures and deficiency or overload of trace elements. The objective of this review and meta-analysis was to examine the present knowledge on the concentrations of the most investigated trace metals, including zinc, copper, selenium, and magnesium, in patients with epilepsy and febrile seizures. The PubMed and Scopus databases were searched to identify case-control studies that compared the concentration of zinc, copper, magnesium, and selenium in serum, hair, or cerebrospinal fluid between patients with epilepsy/febrile seizures and controls. A total of 60 articles were included in the present study (40 pertaining to epilepsy and 25 pertaining to febrile seizures). The serum concentration of zinc in nontreated patients with epilepsy was significantly higher than in controls (P=0.034). There were significantly reduced serum concentrations of zinc (P=0.018) and selenium (P=0.012) in patients with febrile seizures compared with controls. The concentrations of copper, magnesium, and zinc were all significantly altered in patients with epilepsy who received antiepileptic drugs compared with untreated patients with epilepsy. Designing treatments to selectively restore zinc levels may be a strategy for treating patients with epilepsy. It is still unclear whether these ions are causal to, or a cofactor in, the development of epilepsy. Knowledge of the effects of various antiepileptic drugs on trace element homeostasis could potentially be used to effectively guide appropriate therapeutic strategies in the future. [ABSTRACT FROM AUTHOR]

Juvenile-onset systemic lupus erythematosus (JSLE) is a multisystem autoimmune disease in which both the genetic and environmental factors seem to be involved in the etiopathogenesis of the disease. The aim of this study was to evaluate the association of programmed cell death 1 (PDCD1, also called PD-1) gene polymorphisms with JSLE susceptibility in Iranian population. In this case-control association study, threePDCD1SNPs, includingPD-1.1G/A,PD-1.3G/A andPD-1.9C/T were genotyped in 50 Iranian patients with JSLE and 202 healthy unrelated controls, using PCR-RFLP method. ThePD-1.1A allele was found to be more frequent in the case group compared with controls (6% vs. 1.5%,p = 0.024). Moreover, the GG genotype was less frequent in cases than in controls (88% vs. 97%,p = 0.021). The otherPDCD1SNPs did not show association. At the haplotypic level, no significant differences was recognized between the two groups of case and control neither for the GAC (PD-1.1G,PD-1.3A,PD-1.9C) nor for the GGC haplotype (PD-1.1G,PD-1.3G,PD-1.9C). Our findings support the influence of thePD1.1A SNP on the development of JSLE in Iranian population. [ABSTRACT FROM PUBLISHER]

Background: Tertiary pediatric hospitals usually provide excellent clinical services, but such centers have a lot to do for educational perfection. Objectives: This study was performed to address under-graduate educational deficits and find feasible solutions. Patients and Methods: This cross-sectional study was done in a target population of 77 sixth year undergraduate medical students (response rate = 78%) who spent their 3-month pediatric rotation in the Children’s Medical Center, the Pediatrics Center of Excellence in Tehran, Iran. The Dundee ready educational environment measure (DREEM) instrument was used for assessing educational environment of this subspecialized pediatric hospital. Results: Among 60 students who answered the questionnaires, 24 were male (40%). Participants’ age ranged from 23 to 24 years. The mean total score was 95.8 (48%). Comparison of scores based on students’ knowledge showed no significant difference. Problematic areas were learning, academic self-perception, and social self-perception. Conclusions: Having an accurate schedule to train general practitioner, using new teaching methods, and providing a non-stressful atmosphere were suggested solutions. [ABSTRACT FROM AUTHOR]

Autonomy is usually considered as a main principle in making decisions about individuals' health. Children and particularly adolescents have the capacity to take part in medical decision-making to some extent. For the most part the parent-doctor-child/adolescent triangle sides are essentially in agreement, but this may not be true in some cases, causing physicians to face problems attempting to determine their professional duties. According to Islamic jurisprudent upon reaching the age of Taklif (15 full lunar years for boys and 9 full lunar years for girls) no one can be treated as incompetent based on mental immaturity unless his or her insanity or mental immaturity is provend Moreover the Islamic Sharia, decrees that parents should lose their authority to make medical decisions for their children, if their bad faith or imprudence is proven, in which case a fit and proper person or an institution will be appointed to make decisions in this respect based on the child's best interests. [ABSTRACT FROM AUTHOR]

Neutropenia is a reduction of the absolute neutrophil count (ANC), which could be seen in different conditions, while its association with a number of primary immunodeficiency diseases has been reported. This study was performed in all neutropenic patients who were admitted in a referral pediatric hospital during a 6-year period (2006-2011). One hundred and forty patients with ANC of below 1500/mm3 were investigated in this study. The most common causes of neutropenia were severe congenital neutropenia (41%), aplastic anemia (19%), cyclic neutropenia (11%), hyperimmunoglobulin M syndrome (9%), and fanconi anemia (7%). The patients experienced their first manifestation at a median age of 1 year, while the median diagnostic age was 21 months. Parental consanguinity was present in about half of the cases. The most common clinical manifestations of the patients were sinusitis (62 cases), periodontitis (51 cases), acute diarrhea (39 cases), pneumonia (38 cases), abscess (36 cases), skin rashes (35 cases), and otitis media (31 cases). Twenty two patients (16%) died during the study period. Considering the differential diagnosis of neutropenia, making the diagnosis and appropriate treatments are the keys in management of patients with neutropenia to avoid further complications. [ABSTRACT FROM AUTHOR]

Objective: Physicians’ awareness about pediatric health problems is very important in health system. This has not been investigated in Iran as yet. Therefore this study was conducted to characterize the knowledge of the Iranian physicians which has direct association with health status of children. Methods: One hundred and four physicians, mainly pediatric specialists (58.6%) working in the state hospitals (45.1%) were enrolled. They filled a valid and reliable questionnaire, containing 26 questions about basic and important pediatric issues before and after an educational pediatric program (EPP). Findings: Thirty nine (37.5%) physicians answered correctly more than 2/3 of all questions (passed the examination) before EPP, which increased to 42.3% after EEP. Subgroup analysis showed that the total scores of general practitioners (P=0.007) was significantly increased after the EPP. Moreover, physicians with shorter practicing time (P=0.006) and those with shorter time past graduation (P=0.01) had a significant improvement in their total scores after the program. The best scores of educational issues were documented in growth and development (16.0%; P=0.04), followed by dermatology (9.2%, P=0.04), urology (9.1%; P=0.04), and asthma and allergy (9.0%, P=0.04). Conclusion: This study revealed that there are gaps in the knowledge of professionals about the pediatric issues. [ABSTRACT FROM AUTHOR]

Objective: Alpha1-antitrypsin deficiency (A1ATD) is the most important indication for liver transplantation in children. The gene frequencies vary in different ethnic groups. In the present study, we attempt to determine the frequencies of the most common defective alleles, Z and S, in Iranian children suffering from idiopathic neonatal cholestasis. Eighty-seven infants were typed for Z and S alleles. Methods: In a single center study, 87 consecutive liver biopsies from infants with cholestasis were reviewed and patients with neonatal cholestasis enrolled in the study and cases with confirmed biliary tract atresia excluded. Formalin fixed paraffin embedded blocks were used for DNA extraction. AAT genotype was determined by polymerase chain reaction (PCR) assay and amplification of the two most common deficiency variants, S and Z alleles, and then sequencing of PCR products. Findings: There were 48 (55.2%) males and 39 (44.8%) females, with a median age of 60 days. Out of 87 of the study subject, 2 (2.2%) were heterozygous for the S allele, and no ZZ, SS or MZ individual was found in the patients. No other polymorphism was found in the sequencing results. Conclusion: In comparison to other populations, AAT deficiency seems not to be an important etiologic factor for neonatal cholestatic liver disease in Iran; however, further studies are recommended to estimate the true mutant gene frequencies. [ABSTRACT FROM AUTHOR]

Specific alleles at the HLA-DRB1, -DQA1, and -DQB1 loci seem to be associated with variable risks of developing type 1 diabetes (T1D). This study assessed the distribution of HLA-DR and -DQ alleles among Iranian T1D patients and healthy controls. In this study, HLA-DRB1, -DQA1, and -DQB1 alleles were determined in 100 children with T1D and 100 unrelated healthy controls. The following alleles were found to have a strong positive association with T1D: DRB1*0301, DRB1*0401, DRB1*0402, DQA1*0301, DQA1*0501, DQB1*0201, and DQB1*0302. Meanwhile, protective associations were found for DRB1*1001, DRB1*1101, DRB1*15, DRB1*16, DQA1*0102, DQA1*0103, DQB1*0301, DQB1*0501, and DQB1*0602 alleles. The haplotypes found most frequently among patients with T1D were DRB1*0301-DQA1*0501-DQB1*0201, DRB1*0401-DQA1*0301- DQB1*0302, and DRB1*0402-DQA1*0301-DQB1*0302, whereas DRB1*1101-DQA1*0501-DQB1*0301 and DRB1*16-DQA1*0102- DQB1*0501 haplotypes were negatively associated with the disease. These results confirm the previously reported association of specific HLA-DR and HLA-DQ alleles and haplotypes with T1D in Iranian population. The notable difference was the identification of DRB1*16-DQA1*0102-DQB1*0501 as a protective haplotype and the absence of a negative association of DRB1*1301-DQA1*0103-DRB1*0603 with T1D. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) is a rare condition characterized by fever, hepatosplenomegaly, and cytopenia, and widespread accumulation of lymphocytes and histiocytes, sometimes with hemophagocytosis, primarily involving the spleen, lymph nodes, bone marrow, and liver. HLH can either occur sporadically (secondary HLH) or as part of a familial syndrome (primary HLH), including familial HLH and the distinct immunodeficiency syndromes. Herein the authors report 6 Iranian patients with primary HLH and their outcome from a single tertiary-care center. [ABSTRACT FROM AUTHOR]

Primary immunodeficiency diseases (PIDs) consist of a group of genetic disorders that predispose the patients to immune-mediated complications. The aim of this study was to assess the knowledge of Iranian general practitioners and pediatricians about PIDs. A questionnaire consisting 52 closed questions on clinical symptoms, laboratory data, associated syndromes and management of PIDs patients was made valid and reliable by a pair pilot study. Then the questionnaire was filled by pediatricians, general practitioners and pediatric residents from different regions of Iran. Totally, 333 physicians (50 general practitioners, 52 pediatric residents, 182 pediatric specialists, and 49 pediatric sub specialists) participated in this study. The mean total score was 55.9±14.3 (i.e. about 29 correct answers out of 52 questions). One hundred and five participants (31.9%) answered correctly more than two third of all questions. In order to qualitatively compare the groups a ranking system was used. Total scores was significantly different between physicians groups (p<0.01). Pediatric subspecialties gained the highest rank, which was significantly over the other participants (p<0.05). This study showed that there is a considerable lack of awareness on PIDs in physicians. This may be one of the major reasons in late diagnosis and the delay in adequate treatment deteriorating patients' morbidity and mortality. Retraining classes and reconsidered educating schedules are needed as an efficient strategies and improving physicians' knowledge about PIDs. [ABSTRACT FROM AUTHOR]

Primary immunodeficiency diseases (PIDs) are a heterogeneous group of inherited disorders that cause individuals to be prone to a variety of clinical manifestations, such as infections, autoimmunity, and malignancies. Early diagnosis and adequate treatment of these disorders can reduce morbidity and mortality and provide a relatively high quality of life. In Iran, recent advances in clinical immunology and in the identification of immunodeficiencies have led to reductions in diagnostic delay and severe complications in patients with PIDs. Autosomal recessive and multifactorial types of PID seem to be more common in Iran because of high rates of consanguine marriages and, probably, the genetic background of its ethnic groups. These facts necessitate special diagnostic and treatment approaches, but at the same time reveal an opportunity to observe novel phenotypes and genetic defects. [ABSTRACT FROM AUTHOR]

Objective: Beta-thalassemia major is an autosomal recessive disease causing severe and hemolytic anemia, which begins about 2-6 months after birth. Iron overload, which arises from recurrent transfusion and ineffective erythropoiesis, can enhance oxidative stress in thalassemic patients. The aim of this study was to evaluate the serum total antioxidant capacity of patients with ß- Thalassemia major. Methods: Sixty six Iranian patients with ß-thalassemia major and 66 age-gender matched controls were evaluated for serum total antioxidant status (TAS), uric acid (UA), bilirubin and albumin. In addition, serum ferritin and transaminases were recorded in these subjects. Findings: Significant increases of TAS, UA, and bilirubin were observed in the patient group, compared with the control group (P<0.01). Mean TAS and bilirubin in male patients was higher than in females (P=0.005 and P=0.008, respectively). There was also direct correlation between TAS and albumin (P<0.001), bilirubin (P<0.001) and UA (P=0.002). Conclusion: Endogenous antioxidants such as ferritin, UA and bilirubin can result in increased level of TAS in the patients with Beta-thalassemia major. Compensatory excess of TAS to oxidative stress could also be the reason for difference between our findings and previous studies. [ABSTRACT FROM AUTHOR]

Background: Iran is ethnically, linguistically and religiously diverse. However, little is known about the population genetics of Iranian religious communities. Aim: This study was performed in order to define the different paternal components of the Iranian gene pool. Subjects and methods: Fourteen Y chromosome bi-allelic markers were analysed in 130 male subjects from Assyrian, Armenian and Zoroastrian groups in comparison with 208 male subjects from three Iranian Muslim groups. Results: Among the three Iranian Muslim groups, the Uromian people possessed a particularly close genetic relationship to the Armenian, whereas the Zoroastrian group was different from the Uromian, but had a close genetic relationship to the two other Muslim groups (Kermanian and Shirazian). The genetic results indicate a relationship between Armenian and Assyrian groups in Iran and a clear distinction of the former from the Zoroastrian group. However, Assyrians had elevated frequency (40%) of R**(xR1a) and low frequency (11%) of J. Conclusion: The results of this study may suggest that the Assyrian population either experienced Eurasian gene flow (possibly from Armenia) or that enforced relocations and expulsion of conquered people with different origin led to the integration of descendants with R haplogroup. This could also be due to genetic drift due to small population size and endogamy resulting from religious barriers. [ABSTRACT FROM AUTHOR]

Pediatric immunology came into sight in the second half of 20th century, when pediatricians and basic immunologists began to give attention to diagnosis and treatment of children with primary immunodeficiency diseases (PIDs). Understanding the genetic and mechanistic basis of PIDs provides unique insight into the functioning of the immune system. By progress in basic and clinical immunology, many infrastructural organizations and academic centers have been established in many countries worldwide to focus on training and research on the immune system and related disorders. Along with progress in basic and clinical immunology in the world, pediatric immunology had a good progress in Iran during the last 33-year period. Now, patients with PIDs can benefit from multidisciplinary comprehensive care, which is provided by clinical immunologists in collaboration with other specialists. Patients with history of recurrent and/or chronic infections suggestive of PIDs are evaluated by standard and research-based testing and receive appropriate treatment. The progress in PIDs can be described in three periods. Development of training program for clinical fellowship in allergy and immunology, multidisciplinary and international collaborative projects, primary immunodeficiency diseases textbooks, meetings on immunodeficiency disorders, improvement in diagnosis and treatment, and construction of Iranian primary immunodeficiency association, Students' research group for immunodeficiencies, Iranian primary immunodeficiency registry, and the immunological societies and centers were the main activities on PIDs during these years. In this article, we review the growth of modern pediatric immunology and PIDs status in Iran. [ABSTRACT FROM AUTHOR]

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a costimulatory molecule expressed by activated T cells. This study was performed to investigate the allele and genotype frequencies of CTLA4 gene polymorphisms in Iranian patients with ankylosing spondylitis (AS). One hundred and fifty-seven patients with AS and 103 controls were included in this study. Polymorphisms of CTLA4 gene at positions +49 (in exon 1), −318, and −1,147 (in the promoter region) were studied on the genomic DNA using PCR restriction fragment-length polymorphism method. The frequencies of the T allele at position −1147 in the patients with AS was significantly increased in comparison with the control group (11% vs. 5%, P = 0.004); whereas the frequencies of C allele at the same position were significantly decreased in the patient group (89% vs. 95%, P = 0.004). Comparison of genotype frequencies at this position showed that the frequency of CT genotype in comparison with other genotypes was overrepresented in the patient group (20% vs. 8%, P = 0.012), while the CC genotype in comparison with other genotypes was decreased (79% vs. 91%, P = 0.012). There was no significant difference on frequencies of genotypes at the positions −318 and +49. This study could suggest an association between specific allele in the promoter region of CTLA4 gene and AS disease. [ABSTRACT FROM AUTHOR]

X-linked Agammaglobulinemia (XLA) is a hereditary immunodeficiency, characterized by an early onset of recurrent bacterial infections, hypogammaglobulinemia and markedly reduced B lymphocytes number. In order to determine the association of neutropenia among Iranian patients with XLA, hospital records of 30 patients with confirmed XLA in Children Medical Center Hospital, were reviewed. Eight out of 30 XLA patients (26.7%) developed neutropenia during the course of the disease. In two patients, episodes of neutropenia were identified before or at the time of diagnosis of XLA. Other six patients whom were not visited regularly and did not receive periodical immunoglobulin replacement therapy experienced neutropenia after diagnosis of XLA. Neutropenia in XLA is mainly associated with infection and is resolved with intravenous immunoglobulin replacement and antibiotics therapy. [ABSTRACT FROM AUTHOR]

Background: Cystic fibrosis (CF) is the most prevalent lethal autosomal recessive disease with a broad spectrum of phenotypes. Mutation of ΔF508 in the CFTR gene is the most important and lethal mutation in CF, which contains 70% of all predisposing mutations for CF worldwide. Objectives: Determining frequency of genotypes with ΔF508 mutation in CFTR gene, and evaluation of correlation between genotype and phenotype of Iranian patients with CF. Patients and Methods: Thirty six patients were included in this cross sectional study. ΔF508 mutations in both alleles of the CFTR gene were checked. Results: Among 36 pediatric patients, ΔF508 mutation was detected in 9 (25%) patients; 2 patients were heterozygous, and 7 patients homozygous for this mutation. From overall 72 tracked alleles, 11 (15.2%) were found to have ΔF508 mutations. Differences in prevalence of dyspnea and bronchiectasis were significant in homozygote group, compared with non-mutated group for ΔF508. Conclusions: It seems that more ΔF508 mutated alleles lead to more severe symptoms of CF. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Provides data on Iranian patients with primary immunodeficiency diseases (PID), classified according to World Health Organization criteria and diagnosed between 1981 and 2001. Frequencies of predominantly antibody deficiency and phagocytic disorders; Most frequent disorders; Importance of PID registries for medical staff.

Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease characterized by episodic fever and inflammatory polyserositis, which could lead to a variety of manifestations, including recurrent abdominal pain. Herein, a 12-year-old boy who has suffered from fever and bloody diarrhea since early childhood is described. All structural and underlying disorders leading to bleeding were excluded. Genetic studies indicated compound heterozygote mutations of M680I/R761H in the MEFV gene, which confirmed the diagnosis of FMF. Therefore, treatment with colchicine was started, which led to symptom relief. As gastrointestinal manifestations appear to be the main features of FMF, bloody diarrhea could also be considered an initial symptom of FMF. [ABSTRACT FROM AUTHOR]

Celiac disease has been shown to be associated with type 1 diabetes mellitus. We conducted this study to determine the frequency of celiac disease in a group of Iranian diabetic children. Ninety-six patients with type 1 diabetes mellitus were tested for anti-tissue transglutaminase antibodies. Six patients (6.25%) were seropositive, and histopathological changes were compatible with celiac disease in intestinal biopsy. [ABSTRACT FROM AUTHOR]

Clinical immunology and its subset topics are rather newly emerging medical fields in Iran as well as other developing countries. Primary immunodeficiency diagnosis and treatment were revolutionized in the late 1970s; a period of time that coincided with the establishment of the Division of Clinical Immunology and Allergy at the Children's Medical Center, Tehran. Subsequently, the launch of fellowship training programs (in 1988), the development of a national Iranian Primary Immunodeficiency Diseases Registry (in 1999), the inauguration of Research Center for Immunodeficiencies (in 2009), and recently, the national primary immunodeficiency network (in 2016) significantly changed the picture of disease management during the last 40 years. In this review, we seek to elucidate the most important past events, current challenges and future directions regarding the field of primary immunodeficiency. [ABSTRACT FROM AUTHOR]

MRD detection with allele-specific oligonucleotide-quantitative polymerase chain reaction (ASO-qPCR) and using clone-specific immunoglobulin/T cell receptor rearrangements is considered as a powerful prognostic factor in acute lymphoblastic leukemia (ALL). In the present study, we evaluated an ASO-qPCR assay for MRD quantification in peripheral blood (PB) samples of adult patients with ALL. DNA was isolated from PB samples of patients with newly diagnosed ALL. They were first investigated by multiplex-PCR assay to identify V/J usage. An ASO-qPCR technique was then applied for 2.5-year monthly MRD quantification for detection of patient-specific Ig/TCR receptor rearrangements as a molecular target. From 98 patients who were diagnosed as ALL, 72 (73.5%) were enrolled in the present study for MRD detection. MRD was successfully quantified in patients with 1-month interval time. MRD level at the end of induction therapy up to day 88 was the only significant prognostic factor. Regarding MRD level, patients were categorized into two groups of low and high-risk. 2.5-year OS in all three time points (days 28, 58 and 88) were significantly lower in high-risk group (P < 0.008). The results of the 2.5-year MRD detection indicate that MRD level at the end of induction up to about 6 months after the first diagnosis was associated with clinical outcome. This study may highlight the usefulness of PB and the definitions of cut-off level for early prediction of relapse and for stratifying ALL patients. Short-interval time points and frequent PB sampling to monitor MRD level is suggested for early clinical relapse prediction and clinical management of the disease. [ABSTRACT FROM AUTHOR]

The role of microbiota in health and disease is the subject of rigorous investigation. Several studies have demonstrated that microbiota and the pattern-recognition receptors contribute to intestinal tumourigenesis; the exact mechanism of which is still obscure. MyD88 is the downstream effector of all Toll-like receptors (TLRs) except TLR3. However, the alternative MyD88-independent pathway is functional downstream of not only TLR3, but also TLR1/2, 2/6, 4, and 5. TLR4 stimulation with intraperitoneal lipopolysaccharide exerts distinct functional effect on the intestinal motility via MyD88-dependent and-independent pathways. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented wherein the authors discuss a study addressing issues related to the enforcement of and compliance with current prevention guidelines among splenectomized patients in a tertiary care setting in the June 2012 issue of the journal.

The article presents an abstract on the case study of a 9-year-old girl with recurrent ear infections and failure and also extremely elevated Immunoglobulin M (IgM) and significantly decreased IgG and IgA.

Summary: Background: The bacille Calmette–Guérin (BCG) vaccine is a widely practiced vaccine, which is useful for prophylaxis against tuberculosis. Disseminated BCG infection (BCG-osis) is one of the most important complications of this vaccine and can be seen in patients with an underlying immunodeficiency. This study was performed to determine the underlying defects in patients with BCG-osis. Methods: Immunological evaluation was performed in all children who developed BCG-osis after vaccination in Tabriz, Iran. Results: BCG-osis was documented in eight patients following vaccination. Axillary adenitis was detected in seven patients, and hepatosplenomegaly was also found in seven patients. Immunological studies revealed low serum IgG, IgM and IgA levels in all patients. Further investigations for enumeration of the lymphocyte sub-population revealed severe combined immunodeficiency (SCID) in all the patients. Three patients had T−B+NK− SCID, four had T−B−NK+ SCID, and one had T−B+NK+ SCID. Unfortunately, all the patients died due to the severe disseminated BCG infection. Conclusions: Inoculation of live vaccines such as BCG should be postponed for a few months in suspected cases of primary immunodeficiency disease, until appropriate screening tests exclude this diagnosis; vaccination should then be performed in those with an intact immune system. [Copyright &y& Elsevier]

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor with poor prognosis and high potential of dispersion to other brain tissues in adult. Effective and modern choices of treatment including chemotherapy with alkylating agents marginally extend survival of GBM. However, alkylating agents can lead to highly harmful mismatch during DNA replication causing apoptosis and cell death. Accordingly, O6-Methylguanine-DNA methyltransferase (MGMT) removes alkyl adducts, thereby causing resistance to alkylating drugs. Single-Nucleotide Polymorphisms (SNPs) in MGMT promoter region may play a role in the regulation of MGMT expression and prediction of glioma development risk. In order to evaluate the clinical significance of rs1625649 SNP in the MGMT promoter region of glioblastoma, genomic DNA from a series of 54 patients with GBM and 50 healthy individuals in Iranian population were collected for tetra ARMS PCR amplification. None of the "A" or "C" alleles were associated with tumor occurrence, the "AA" genotype was more frequent in healthy subjects, and the "AC" genotype was 4.6 times more common in patients with GBM. The longest survival time was observed in the "CC" genotype; however, this difference was not statistically significant. On the other hand, homozygous rs1625649 (AA genotype) was significantly associated with a better survival than the cases with heterozygous rs1625649 (CA genotype) or wild type rs1625649 (CC genotype), predicting better response to temozolomide-based chemotherapy. [ABSTRACT FROM AUTHOR]