Regulatory T-lymphocyte subsets in children with chronic immune thrombocytopenia after high-dose of dexamethasone.

BACKGROUND: Immune thrombocytopenia (ITP) is an acquired autoimmune disease. This study's objective was to estimate the variations in the population of CD4+CD25+High FoxP3+ cells (CD4+ regulatory T-lymphocytes; Tregs) in previously untreated children with chronic ITP managed in Assiut University Hospitals, as well as to evaluate the efficacy of high-dose dexamethasone (HD-DXM) in these patients. METHODS: In this study, we investigated the frequencies of T-lymphocyte subsets in 27 untreated children with chronic ITP. RESULTS: Prior to treatment, the percentages of CD4+CD25High cells and Tregs were significantly lower in the chronic ITP group compared to the control group (p = 0.018 and p < 0.0001, respectively). After treatment with HD-DXM, Tregs and platelets were significantly increased in these patients (p < 0.0001 for both). CONCLUSIONS: Our results suggest that Tregs are deficient in children with chronic ITP and that HD-DXM immunosuppressive therapy can restore the levels of these cells. IMPACT: CD4+CD25High cells and Tregs were significantly lower in children chronic ITP compared to healthy control. HD-DXM treatment led to significantly increased Tregs and platelets in these patients. Our results suggest that Tregs are deficient in children with chronic ITP and that HD-DXM immunosuppressive therapy can restore the levels of these cells.

Serum Galanin in Children with Autism Spectrum Disorder.

Recent studies have attempted to measure several biomarkers to understand the complex interactions of the anatomic systems that may be involved in autism spectrum disorder (ASD). In CNS, galanin takes part in a variety of pathological and physiological processes. Prior research has indicated it is involved in several neuropsychiatric disorders and has a role in inhibiting the neuronal firing and release of serotonin, norepinephrine, and acetylcholine. To date, serum galanin levels have not been investigated in the context of ASD. This study aimed, therefore, to compare the serum galanin levels of children with ASD and healthy controls and to reveal any association between galanin level and the severity of ASD, as well as other psychological and demographic parameters. Serum galanin levels were measured by radioimmunoassay in 116 children with ASD and 98 healthy children. We observed significantly increased serum concentrations of galanin in children with ASD relative to healthy children. Moreover, children with severe ASD had significantly higher galanin levels than those with less severe disease. We also confirmed significant positive correlations between galanin and psychiatric parameters in children with ASD. For the first time, we suggest a possible correlation between serum galanin and the degree of ASD severity. Increased galanin levels may play a role in the pathogenesis of ASD.

Regulatory T-cell phenotypes in children with sickle cell disease.

BACKGROUND: Regulatory T cells (Tregs) are linked to a reduction in alloreactive immune responses, but few studies have investigated the impact of hydroxyurea (HU) therapy on Tregs in sickle cell disease (SCD). METHODS: Our case-controlled study presented here included two groups, the first comprising 60 pediatric SCD patients, 30 of whom did not receive any treatment and 30 who received HU, and the second group consisting of 30 healthy controls. Flow cytometry was used to evaluate the percentage of CD4+CD25+highFoxp3+ Tregs present and their phenotypes. RESULTS: The percentage of CD4+CD25+high Tregs was significantly increased in untreated SCD patients in comparison to treated SCD patients and controls. Conversely, treated SCD children had a lower percentage of CD4+CD25+high Tregs than controls. In addition, a significant increase in the percentage of CD4+CD25+highFoxp3+ Tregs was found in untreated SCD patients, compared to in HU-treated patients and controls. The percentage of naive CD45RA+ Tregs was significantly decreased in untreated SCD patients when compared to other groups. CONCLUSIONS: Among children with SCD, HU treatment exhibited significant qualitative and quantitative effects on Tregs by decreasing their frequency, and increasing the proportion of naive CD45RA+ Tregs and reducing levels of the most suppressive Tregs: HLA-DR+, CD39+, and CD69+. IMPACT: Among children with, SCD, HU treatment exhibited significant qualitative and quantitative effects on Tregs. HU treatment in SCD decreases the frequency of Tregs, as well as the levels of the most suppressive Tregs: HLA-DR+, CD39+, and CD69+. At the same time, HU increases the proportion of naive CD45RA+ Tregs. Our study showed the impact of HU therapy on Tregs in children with SCD.

Ewing sarcoma outcomes in a country with limited resources: Egypt as an example.

As the scarcity of published research that comprehensively and meticulously analyzed the patient, disease, and treatment factors of prognostic significance in Ewing sarcoma (EWS) in Egypt; This study aimed at assessing survival outcomes of EWS in Upper Egypt, delineating factors of prognostic significance in comparison to other leading oncology centers in Egypt and internationally. By retrospectively reviewing medical records of 85 patients with a verified diagnosis of EWS in the period from 2001 to 2015 at Pediatric and Medical Oncology Departments at South Egypt Cancer Institute; We gathered data relevant to the patient, disease, and treatment variables of the study. Survival was estimated using the Kaplan Meier method and differences between various groups were determined by log rank test. Univariable and multivariable analyses were performed using Cox regression. With a median follow-up period of 62.7 months (95% CI 52.2-73.2, SE=5.4) for the study patients, the estimates of event-free survival (EFS) and overall survival (OS) at 3 and 5 years were 42.1% and 50.6%, and 40.8% and 48.5%, respectively. Metastatic disease at initial presentation (HR=8.91, 95% CI, 4.00-19.9; P<0.0001) stood as the most powerful predictor of OS in the multivariable analysis, followed by surgery used as a local modality (HR=0.16, 95% CI, 0.06-0.44; P=0.0004). Response to neoadjuvant chemotherapy (HR=2.61, 95% CI, 1.11-6.13; P=0.028), primary tumor size (HR=2.49, 95% CI, 1.03-6.03; P=0.044) were also shown to be significantly associated with OS. Radiotherapy as a local modality, whose effect, apparently shown to increase the hazard of events occurrence in the univariable analysis, an effect that was reversed to reveal EFS advantage (HR=0.41, 95% CI, 0.18-0.95; P=0.036) after control of other variables. With 5-year OS of 48.5%, our survival results were comparable to those previously published from Egypt; however, differences still exist between centers due to varied representative study samples. However, outcomes in Egypt in general are still inferior to internationally published studies.

Increase in polymorphonuclear myeloid-derived suppressor cells and regulatory T-cells in children with B-cell acute lymphoblastic leukemia.

Our study aimed to evaluate the levels of MDSCs and Tregs in pediatric B-cell acute lymphoblastic leukemia (B-ALL), their relation to patients' clinical and laboratory features, and the impact of these cells on the induction response. This study included 31 pediatric B-ALL patients and 27 healthy controls. All patients were treated according to the protocols of the modified St. Jude Children's Research Hospital total therapy study XIIIB for ALL. Levels of MDSCs and Tregs were analyzed using flow cytometry. We observed a reduction in the levels of CD4 + T-cells and an increase in both the polymorphonuclear MDSCs (PMN-MDSCs) and Tregs. The frequencies of PMN-MDSCs and Tregs were directly related to the levels of peripheral and bone marrow blast cells and CD34 + cells. Complete postinduction remission was associated with reduced percentages of PMN-MDSCs and Tregs, with the level of PMN-MDCs in this subpopulation approaching that of healthy controls. PMN-MDSCs and Tregs jointly play a critical role in maintaining an immune-suppressive state suitable for B-ALL tumor progression. Thereby, they could be independent predictors of B-ALL progress, and finely targeting both PMN-MDSCs and Tregs may be a promising approach for the treatment of B-ALL.

Dendritic cells and monocyte subsets in children with Gaucher disease.

BACKGROUND: There are minimal data on the frequencies of monocyte subsets and dendritic cells (DCs) in children with Gaucher disease (GD), as nearly all previous studies have involved adult patients. Consequently, we aimed to describe the changes in these cell subpopulations in children with GD type 1 who were on regular enzyme replacement therapy (ERT). METHODS: This case-control study included 25 children with GD1 and 20 healthy controls. All participants underwent investigations such as complete blood count and flow cytometric assessment of DC and monocyte frequencies and phenotype. RESULTS: We found that GD1 children had significantly reduced percentages of both types of DCs, i.e., plasmacytoid DCs and myeloid DCs, compared to the control group. There was also a significant reduction in absolute monocyte numbers and percentage of classical monocyte. Moreover, the GD1 children had higher frequencies of non-classical and intermediate monocytes than the control group. CONCLUSIONS: Our results so far indicate that, when compared to the control group, the GD1 children had significantly reduced total and classical monocyte, with significantly decreased frequencies for both types of DCs. These changes can contribute to immunological abnormalities in pediatric patients with GD1. IMPACT: Children with Gaucher disease type 1 (GD1) have significantly reduced total and classical monocyte frequencies, with decreasing percentages for both types of dendritic cells. GD1 children had significantly reduced frequencies of myeloid and plasmacytoid dendritic cells as compared to the controls. The GD1 children also had significant changes in monocyte subsets when compared to the controls. Our results show that monocytes and dendritic cells' significant changes could contribute to immunological abnormalities in pediatric patients with GD1.