Interferon gamma: is it a co-player in the pathogenesis of idiopathic nephrotic syndrome

Introduction: Idiopathic nephrotic syndrome (INS), the most common form of NS in childhood, was considered 4 decades ago as a systemic disorder of T cells, mediated through its released cytokines. To date, the exact incriminated cytokine or immunological mediator is not properly defined. Interferon gamma (IFN-γ), a pro-inflammatory cytokine, is thought to have a role in the provocation of the T cell mediated INS relapse, through promotion of T helper1 (Th1) differentiation and suppression of regulatory T cells (Treg). Aim of the study: to evaluate the immunopathogenic role of IFN-γ in children with steroid sensitive idiopathic nephrotic syndrome (SSNS) through monitoring the changes in its levels with disease course. Methods: This study included twenty-five newly diagnosed children with SSINS. They were all given full dose prednisolone, evaluated at initial diagnosis and at full remission as regards the serum level of IFN-γ. Results: Serum levels of IFN-γ were lowermost at time of diagnosis and increased with remission on corticosteroids. Conclusions: this study points to a role for the lower serum IFN-γ at diagnosis, in the immunopathogenesis of INS than at remission and the rise in its serum level might be a marker of remission induction, however this awaits confirmation in larger scale studies. Studies on renal biopsy specimens are needed to determine the exact renal in situ levels and effects of IFN-

Study of obesity associated proopiomelanocortin gene polymorphism: Relation to metabolic profile and eating habits in a sample of obese Egyptian children and adolescents

AbstractBackgroundMelanocortinergic system represents a known system involved in the central regulation of body weight with the central proopiomelanocortin (POMC) neurons forming a potent anorexigenic network. Polymorphisms in the POMC gene locus are associated with obesity phenotypes.AimTo assess the contribution of the POMC gene 9-bp insertional polymorphism in the susceptibility to obesity and its relation to body mass index (BMI) and adiposity-related co-morbidities in obese children and adolescents; as well as binge eating behavior.Patients and methodsFifty obese children and adolescents with simple obesity were screened for Binge Eating Disorder (BED) by The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), they were compared to 50 age, sex and pubertal stage-matched non obese controls. Anthropometric measurements, blood pressure, abdominal ultrasound for fatty liver, measurement of fasting lipid profile, fasting insulin, fasting blood glucose and assessment of POMC gene 9-bp insertional polymorphism were done.ResultsObese patients had significantly higher anthropometric measurements, blood pressure percentiles, fasting glucose, fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR) and fasting lipid profiles, and higher frequency of occurrence of non alcoholic fatty liver disease and BED. Allelic frequencies of POMC gene 9bp insertional polymorphism were comparable in patients and controls (p=0.956). Fasting insulin levels were significantly higher in the heterozygous cases having the polymorphism than in wild homozygous cases; whereas no difference was observed among the controls.ConclusionThis polymorphism was associated with higher fasting insulin levels in the obese patients only. These findings support the hypothesis that the melanocortin pathway may modulate glucose metabolism in obese subjects indicating a possible gene-environment interaction. POMC variant may be involved in the natural history of polygenic obesity, contributing to the link between type 2 diabetes and obesity

Hormonal control during infancy and testicular adrenal rest tumor development in males with congenital adrenal hyperplasia: a retrospective multicenter cohort study

IMPORTANCE Testicular adrenal rest tumors (TARTs), often found in male patients with congenital adrenal hyperplasia (CAH), are benign lesions causing testicular damage and infertility. We hypothesize that chronically elevated adrenocorticotropic hormone exposure during early life may promote TART development. OBJECTIVE This study aimed to examine the association between commencing adequate glucocorticoid treatment early after birth and TART development. DESIGN AND PARTICIPANTS This retrospective multicenter (n = 22) open cohort study collected longitudinal clinical and biochemical data of the first 4 years of life using the I-CAH registry and included 188 male patients (median age 13 years; interquartile range: 10-17) with 21-hydroxylase deficiency (n = 181) or 11-hydroxylase deficiency (n = 7). All patients underwent at least 1 testicular ultrasound. RESULTS TART was detected in 72 (38%) of the patients. Prevalence varied between centers. When adjusted for CAH phenotype, a delayed CAH diagnosis of >1 year, compared with a diagnosis within 1 month of life, was associated with a 2.6 times higher risk of TART diagnosis. TART onset was not predicted by biochemical disease control or bone age advancement in the first 4 years of life, but increased height standard deviation scores at the end of the 4-year study period were associated with a 27% higher risk of TART diagnosis. CONCLUSIONS AND RELEVANCE A delayed CAH diagnosis of >1 year vs CAH diagnosis within 1 month after birth was associated with a higher risk of TART development, which may be attributed to poor disease control in early life