Genetic association of interleukin 18 (-607C/A, rs1946518) single nucleotide polymorphism with asthmatic children, disease severity and total IgE serum level.

INTRODUCTION: Bronchial asthma is a chronic inflammatory disease. Interleukin 18 (IL-18) single nucleotide polymorphisms (SNPs) can influence IL-18 production and activity. IL-18-607C/A and -137 C/G are two of the commonly studied SNPs of IL-18 due to their role in the etiopathogenesis of allergic diseases. AIM OF THE STUDY: The case control study was conducted to investigate the genetic association between IL-18-607C/A polymorphism and pediatric asthma. Also attempts were made to evaluate the prognostic effect of -607C/A SNP with disease severity and total serum IgE. MATERIAL AND METHODS: The case control study was conducted on 60 asthmatic children and 40 healthy subjects; aged 2 to 12 years. PCR-RFLP was used to detect IL-18-607C/A SNP and total serum IgE level was detected using ELISA technique. RESULTS: Regarding IL-18-607C/A SNP, the frequency of the A allele and CA genotype was significantly higher in asthmatic children compared to healthy control subjects (p < 0.001). Further on, asthmatic children carrying the AA/AC genotype of -607C/A SNP were associated with an increased risk of occurrence of asthma (OR = 6.417; CI = 2.432-17.289). IgE was higher in asthmatic patients carrying the heterozygous CA genotype compared to patients carrying the AA and CC genotypes (p = 0.054). CONCLUSION: The frequency of the heterozygous CA genotype and A allele in IL-18-607C/A SNP was higher in asthmatic children. There is no association between the severity of asthma and -607C/A SNP. Total IgE was higher in patients carrying the CA genotypes compared to patients carrying the AA and CC genotypes, respectively.

Detection of expression of IL-18 and its binding protein in Egyptian pediatric immune thrombocytopenic purpura.

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder, characterized by dysfunctional cellular immunity including the presence of activated platelet specific autoreactive T cells that recognize and respond to autologous platelet antigens. Autoreactive T cells drive the generation of platelet reactive autoantibodies by B cells as well as T-cytotoxic cell-mediated lysis of platelets. Interleukin-18 (IL-18) is a mediator of T helper type 1 cell responses synergistically with IL-12 that initiate and promote host defense and inflammation. IL-18 has a specific binding protein (IL-18BP) which belongs to the immunoglobulin superfamily. In the present study, serum level and messenger RNA( mRNA) expression of IL-18 as well as IL-18BP mRNA expression were measured in peripheral blood mononuclear cells (PBMNCs) of 100 Egyptian pediatric patients with ITP (70 acute and 30 chronic). In addition to this, we recruited 80 healthy volunteers in order to investigate the possible association between the imbalance of IL-18 and IL-18 BP expressions and the pathogenesis of ITP. IL-18 serum level and mRNA expression were not elevated in cases more than in the control group, but IL-18 mRNA was higher in chronic cases when compared to the acute ones (p=0.031) and there was a good negative correlation between the platelet count and serum IL-18. IL-18 BP m-RNA was slightly elevated in cases more than in the control group (95% Confidence interval=1.15-2.01). Our results were not supportive for previous findings of elevated IL18/BP mRNA ratio in ITP patients. This could be referred to the fact that autoimmune diseases are complex genetic disorders, therefore further studies on polymorphisms affecting IL-18 gene expression as well as kinetics of IL-18 expression are required to evaluate the role of interleukin 18 and its binding protein in the pathogenesis of ITP.

WITHDRAWN:Randomized controlled trial of effect of N-acetylcysteine as an antioxidant on iron overload in children with thalassemia major.

Ahead of Print article withdrawn by publisher.

High Serum Endothelin-1 Level is Associated with Poor Response to Steroid Therapy in Childhood-Onset Nephrotic Syndrome.

Nephrotic syndrome (NS) is one of the most common kidney diseases seen in children. It is a disorder characterized by severe proteinuria, hypoproteinemia, hyperlipidemia, and generalized edema resulting from alterations of permeability at the glomerular capillary wall. Endothelin-1 (ET1) has a central role in the pathogenesis of proteinuria and glomerulosclerosis and has a role in assessment of the clinical course of NS in children. This study aims to investigate the relationship between ET1 serum level and the response to steroid therapy in children with primary NS. Serum ET1 levels were evaluated in 55 children with NS. They were classified into two groups: 30 patients with steroid-sensitive NS (SSNS) and 25 patients with steroid-resistant NS (SRNS). The SSNS group was further divided into infrequent-relapsing NS (IFRNS) and steroid-dependent NS (SDNS), while the SRNS group was subdivided into two groups according to renal pathology. ET1 levels were significantly higher in the SRNS group (52.5 ± 45.8 pg/dL) compared to the SSNS group (18.3 ± 17 pg/dL) (P <0.001). Furthermore, ET1 levels were significantly higher in SDNS (54.3 ± 18.6) compared to IFRNS (11.9 ± 7.8, P = 0.001). There was no statistically significant difference in ET1 levels between minimal change disease group and focal segmental glomerulosclerosis group, (P = 0.28). Serum ET1 can be considered as a predictor for response to steroid therapy.