The Risk of the Next Child Getting Affected by Chronic Granulomatous Disease in Families with at Least One Autosomal Recessive CGD Child.

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder more common in autosomal recessive (AR) than X-linked in Iran. This study aimed to assess whether having a child with AR-CGD would increase the likelihood of the next child being affected by CGD. Ninety-one families with at least one child affected by AR-CGD entered this study. Out of the 270 children, 128 were affected by AR-CGD. We used a cross tab for the odds ratio (OR) calculation, in which exposure to a previously affected child and the next child's status were evaluated. This study illustrated that the chances of having another child afflicted with AR-CGD are significantly increased if the previous child had AR-CGD (OR=2.77, 95% CI=1.35-5.69).Althoug h AR disorders affect 25% of each pregnancy, we showed that the chance that the next child would be affected by CGD, given that the previous child was affected, is 2.77 times greater than in families with a normal child. It is recommended to warn families with one or more affected children to evaluate the risk of CGD in their subsequent pregnancies with prenatal diagnosis.

Weaning and extubation from neonatal mechanical ventilation: an evidenced-based review.

Mechanical ventilation is a lifesaving treatment used to treat critical neonatal patients. It facilitates gas exchange, oxygenation, and CO2 removal. Despite advances in non-invasive ventilatory support methods in neonates, invasive ventilation (i.e., ventilation via an endotracheal tube) is still a standard treatment in NICUs. This ventilation approach may cause injury despite its advantages, especially in preterm neonates. Therefore, it is recommended that neonatologists consider weaning neonates from invasive mechanical ventilation as soon as possible. This review examines the steps required for the neonate's appropriate weaning and safe extubation from mechanical ventilation.

The Critical Role of Prenatal Genetic Study in Prevention of Primary Immunodeficiency in High-risk Families: The Largest Report of 107 Cases.

This study aims to investigate the role of prenatal diagnosis (PND) in Iranian couples with a previous history of primary immunodeficiency disorders (PIDD) in their family. All referred couples with a family history of PIDD and a tendency for PND were included in this project. Based on gestational age, chorionic villus sampling (CVS) was performed to analyze the molecular defect of the fetus according to the previous gene defect of the affected case in the family. Postnatal confirmation was performed by immunological screening tests. In a total of 100 cases, CVS was not evaluated in 19 patients due to unwillingness (n=5), late prenatal referral (n=7), miscarriage before CVS (n=3), and female fetus with x-linked diseases in previous children (n=4). In the remaining 81 patients, heterozygous and homozygous mutations were found in 33 and 23 cases, respectively. The hemizygous mutation was obtained in 6 and no pathogenic mutations were found in 19 individuals. Postnatal evaluations revealed that a total of 65 babies were healthy, 32 fetuses were aborted (3 cases before CVS, 2 spontaneous abortions of a healthy and as affected fetus in the CVS subgroup, and 27 cases were aborted due to therapeutic causes). One fetus from the heterozygous subgroup was spontaneously aborted with severe combined immunodeficiency (SCID) and one fetus from the homozygous subgroup that was supposed to be healthy was affected by the autosomal dominant-chronic granulomatous disease (AR-CGD). The diagnostic error was 1.2%. PND is highly recommended in families with a history of PID in their previous child to prevent an affected baby being born and to reduce the government, family, and personal burden of these diseases.

Lupus Erythematosus and Chronic Granulomatous Disease: Report of Four Iranian Patients with AR-CGD and One XL-CGD.

Chronic granulomatous disease (CGD) is a rare genetic disorder of neutrophil activity, resulting in increased rate of recurrent infections with catalase-positive bacteria and fungi, as well as various autoimmune diseases such as sarcoidosis, rheumatoid arthritis, and discoid and/or systemic lupus erythematosus. Few reports have reported lupus erythematosus (LE) in patients with X-linked CGD (XL-CGD) and carriers, and very few in autosomal recessive CGD (AR-CGD). Here, we present 5 patients with CGD developing LE at different ages to emphasize on the importance of appropriate follow-up and treatment in patients with CGD with clinical signs and symptoms of autoimmune diseases and even in those with negative serologic results.

Association of interleukin-6 single nucleotide polymorphisms with juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. Genetics and inflammatory elements seem to act as major underlying factors in its pathogenesis. The aim of this study is to identify the associations between interleukin-6 (IL-6) gene polymorphisms and individuals' vulnerability to JIA in a group of Iranian pediatric patients. Fifty-four patients with JIA were enrolled in this investigation and compared with 139 healthy individuals. Using polymerase chain reaction with sequence-specific primers, cytokine genotyping was performed. The allele and genotype frequencies of two single nucleotide polymorphisms (SNPs) within the IL-6 gene at -174 and +565 positions were assessed. A significant positive association was observed for IL -6 -174 G allele in the patient group (p = 0.02). Furthermore, a positive association was observed in patients with JIA for the GG genotype at the same position (p < 0.01), thus revealing a predisposing effect in JIA patients. On the other hand, a significant negative association was found for IL-6 -174 CG genotype (p < 0.01) in the case group. No significant difference was discovered in both the allelic and genotypic frequencies of IL-6 +565 position between patients and controls. Additionally, haplotype analysis divulged over representation of IL-6 GG haplotype in patient group (p < 0.01) as well as IL-6 CG haplotype in healthy controls (p < 0.01). Certain allele, genotype, and haplotype in IL-6 gene were over expressed in patients with JIA, which probably could render individuals more susceptible to this disease.

Polymorphisms of genes encoding interleukin-4 and its receptor in Iranian patients with juvenile idiopathic arthritis.

As cytokines, including interleukin-4 (IL-4), seem to have a pivotal role in the pathogenesis of juvenile idiopathic arthritis (JIA), this study is aimed at investigating of association of polymorphisms in IL-4 and IL-4 receptor α (IL-4RA) genes with susceptibility to JIA. A case-control study was conducted on 53 patients with JIA and 139 healthy unrelated controls. Single nucleotide polymorphisms of IL-4 gene at positions -1098, -590, and -33, as well as IL-4RA gene at position +1902 were genotyped using polymerase chain reaction with sequence-specific primers method and compared between patients and healthy individuals. At the allelic level, C allele at IL-4 -33 was found to be more frequent in patients compared to control (P value <0.01). At the genotypic level, CC genotype at IL-4 -590 (P value <0.01), together with CC and TT genotypes at IL-4 -33 (P value <0.01), were significantly higher in patients with JIA, while TC genotypes at IL-4 -590 and -33 positions were found to be lower in case group (P value <0.01). At the haplotypic level, IL-4 (positions -1098, -509, -33) TTC, GCC, and TTT haplotypes were significantly lower than controls (P value <0.01, P value = 0.03, and P value = 0.04, respectively). Although, TCC haplotype at the same positions was found to be higher in patients (P value <0.01). Polymorphic site of +1902 IL-4RA gene did not differ between cases and controls. Polymorphisms in promoter region of IL-4 but not IL-4RA genes confer susceptibility to JIA and may predispose individuals to adaptive immune responses.

IL23R gene polymorphism with juvenile idiopathic arthritis and its association with serum IL-17A.

AIM: Interleukin 23 (IL-23) and its receptor (IL-23R) seem to play a major role in differentiation of CD4+ T cells into Th17 cells, induction of IL-17 production, and activation of inflammatory pathways. Recent studies have suggested the association of IL-23R polymorphisms with bone and articular inflammation in diseases such as ankylosing spondylitis and rheumatoid arthritis. The aim of this study was to determine the association between IL-23R polymorphisms and juvenile idiopathic arthritis (JIA). METHOD: A case-control study on 55 patients with JIA and 78 healthy controls was performed. All samples were genotyped for eight single nucleotide polymorphisms (SNPs) of IL23R (rs1004819, rs2201841, rs10889677, rs1495965, rs7517847, rs10489629, rs11209026 and rs1343151), using real-time polymerase chain reaction Taqman genotyping technique. Forty-two patients and 42 healthy controls were chosen randomly to measure the level of serum IL-17A using enzyme-linked immunosorbent assay. RESULTS: Although the heterozygous genotype of rs1004819 (GA) showed a weak, but statistically significant protective effect on polyarticular subtype (P = 0.03), none of the selected SNPs were associated with JIA overall. Indeed the analysis of haplotypes did not show any significant association with JIA. Serum IL-17A level was not significantly different among patients and healthy controls and between JIA subtypes, as well. Moreover, there was no significant correlation between SNPs and serum IL-17A concentration. CONCLUSION: This is the first study of the IL-23R gene in Iranian patients with JIA. Our results did not show any strong association between IL-23R polymorphisms and JIA disease or serum IL-17A levels. The only association was seen between rs1004819 and polyarticular JIA. Further larger studies may help clarify the role, if any, of the IL-23/IL-17 pathway in the pathogenesis of JIA.

Evaluation of the Persian version of modified fatigue impact scale in Iranian patients with multiple sclerosis.

BACKGROUND: Fatigue, a major cause of disability in individuals with multiple sclerosis (MS), is associated with reduced quality of life. The aim of this study was to evaluate the reliability and reproducibility of the Persian version of Modified Fatigue Impact Scale (MFIS) in Iranian patients with MS. METHODS: This study included 15 subjects with clinically definite MS, 15 hospitalized patients with MS, and 15 hospitalized patients with other chronic illnesses (as controls). They filled in the Persian version of the MFIS twice with a three-day interval. MFIS items were analyzed and the correlation coefficient was calculated. RESULTS: THERE WAS A GOOD CORRELATION BETWEEN THE SCORES OF THE TWO MEASUREMENTS (CORRELATION COEFFICIENT: 0.984, P < 0.001) especially in physical and cognitive subgroups. The reproducibility of psychosocial subscale was lower than physical and cognitive subscales. CONCLUSION: According to our findings, the Persian version of the MFIS has a good reliability and reproducibility for assessment of fatigue in patients with MS.

Different pattern of gene mutations in Iranian patients with severe congenital neutropenia (including 2 new mutations).

Severe congenital neutropenia (SCN) is a rare primary immunodeficiency disease. Different genes are found to be associated with SCN, including ELA2, HAX1, WAS, GFI1, G-CSFR and G6PC3. The aim of this study was to find different gene mutations responsible for SCN in Iranian patients. Twenty-seven patients with SCN referred to Immunology, Asthma and Allergy Research Institute during a five year priod 5 years (May 2007 and May 2012), were included in this study. Neutropenia related exons and flanking regions of ELA2, HAX1, WAS, GFI1, G-CSFR and G6PC3 were amplified by PCR and the sequences were analyzed. The results showed different mutations including 4 ELANE mutations, 11 HAX1 mutations and 2 G6PC3 mutations. None of the patients had GFI1 mutation and also one mutation was found in G-CSFR in a patient with ELANE mutation. Ten patients had unknown genetic diagnosis which was compatible with other studies. According to these results, most of the patients showed HAX1 mutations and this finding which significantly differed from other reports, might be related to differences in Iranian ethnicity and also in high rate of consanguineous marriages in Iran.

Prevention and control of infections in patients with severe congenital neutropenia; a follow up study.

Severe congenital neutropenia is one of primary immunodeficiency disorders that characterized by severe neutropenia and is associated with severe systemic bacterial infections from early infancy. Granulocyte colony stimulating factor (GCSF) is clinically used as a treatment for congenital and acquired neutropenia. The aim of this study was evaluation of GCSF (PD- Grastim) in treatment of these patients. Patients with severe congenital neutropenia referred to Immunology, Asthma and Allergy Research Institute between Jan 2007 and Dec 2010 enrolled the study. Other causes of neutropenia were excluded by serial CBC and bone marrow studies, medical and drug histories and immunological tests. Patients were visited and examined monthly to evaluate their CBC and ANC (absolute neutrophil count), GCSF side effects and dosage adjustment. Cytogenetic studies were being done for all the patients for early detection of progression to AML/MDS. From twenty two patients who enrolled this study, 16 patients regularly evaluated. They were ten males and six females, range in age from 2 to 18 years old. Two patients failed to continue our follow up unfortunately and four patients died due to disease complications. Patients were followed for 24 to 48 months. In a period of 12-24 months before treatment, the mean of hospitalization frequency was 3.1 times and duration was 10 days; while during receiving treatment, they decreased to 0.2 times and 3 days, respectively (p<0.01). Also significant increase in mean ANC was observed during follow up (315/µl before treatment versus 1749/µl after 12 month regular treatment). Bone pain was the most common side effect. There have been no evidences of developing AML/MDS up to present time. Treatment with GCSF significantly reduced the duration and the frequency of hospitalization. Because of plausible progression to AML/MDS, regular follow-up of patients should be continued.

Inheritance pattern and clinical aspects of 93 Iranian patients with chronic granulomatous disease.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare immunodeficiency due to a genetic defect in one of the NADPH-oxidase components. We studied CGD inheritance forms (autosomal recessive (AR) or X-linked (XL)) and AR-CGD subtypes in Iran. METHODS: Clinical and functional investigations were conducted in 93 Iranian CGD patients from 75 families. RESULTS: Most of the patients were AR-CGD (87.1%). This was related to consanguineous marriages (p = 0.001). The age of onset of symptoms and diagnosis were lower in XL-CGD compared with AR-CGD (p < 0.0001 for both). Among AR-CGD patients, p47phox defect was the predominant subtype (55.5%). The most common clinical features in patients were lymphadenopathy (65.6%) and pulmonary involvement (57%). XL-CGD patients were affected more frequently with severe infectious manifestations. CONCLUSIONS: Although XL-CGD is the most common type of the disease worldwide, only 12 patients (12.9%) were XL-CGD in our study. The relatively high frequency of AR-CGD is probable due to widely common consanguineous marriages in Iran.