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.

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.

Upregulation of Cytotoxic T-cells in pediatric patients with Gaucher disease.

Cytotoxic (CD8) T-cells and natural killer (NK) cells have a significant immune function role. The ongoing stimulation of immunity and the excessive release of proinflammatory cytokines observed in pediatric patients with Gaucher disease (GD) can affect immune cells. Few studies have looked at the proportion of cytotoxic CD8 T-cells and their subsets in children with GD. A prospective case-control study was performed involving twenty pediatric patients with type 1 GD and twenty healthy age-matched controls. All patients received regular enzyme replacement therapy (ERT) for at least 6 months before the study. Complete blood count and flow cytometric analyses of CD8 T, Tc1, Tc2, NK, and NK T-cells were performed. GD patients showed significantly increased of CD8 T, Tc1 and significantly decreased NK cells frequencies when compared to healthy controls. However, no significant difference in Tc2 and NK T-cells was found between the studied groups. GD patients on regular ERT have increased CD8+ T-cell frequencies, predominantly Tc1, together with a reduction in NK cells than in healthy controls. These crucial immunological changes may contribute to some extent to the pathogenesis and the progression of GD.

Effect of hyperbaric oxygen therapy and Tomatis sound therapy in children with autism spectrum disorder.

Many therapeutic and dietary regimens have been studied for children with autism spectrum disorder (ASD) in the last three decades. We aimed to evaluate the efficacy of hyperbaric oxygen therapy (HBOT) and Tomatis sound therapy (TST) in an Egyptian cohort of children with ASD. This study was a prospective, open label, randomized interventional clinical trial. One hundred forty-six children with ASD with no previous rehabilitation therapy were enrolled in our study. Patients were randomly divided into four groups: the first group received hyperbaric oxygen therapy, the second group received Tomatis sound therapy, the third group received a combination of both modalities, and the fourth group, the control group, received no intervention. We found that the combination of Tomatis sound therapy with hyperbaric oxygen therapy had a superior effect in improving autism symptoms than each intervention alone (CARS after therapy 35.04 ± 13.38 versus 49.34 ± 17.54 before the intervention, p < 0.001). The combination of both modalities may be helpful for children with ASD. The most distinctive evidence that supports the use of combination therapy for ASD is still controversial; however, our study provides some evidence of the benefit of combination therapy for children with ASD. Future studies should use a more sophisticated research design and begin by finding a consistent baseline measure that can be used to evaluate the effects of these therapies for ASD.

Phenotypic continuum of NFU1-related disorders.

Bi-allelic variants in Iron-Sulfur Cluster Scaffold (NFU1) have previously been associated with multiple mitochondrial dysfunctions syndrome 1 (MMDS1) characterized by early-onset rapidly fatal leukoencephalopathy. We report 19 affected individuals from 10 independent families with ultra-rare bi-allelic NFU1 missense variants associated with a spectrum of early-onset pure to complex hereditary spastic paraplegia (HSP) phenotype with a longer survival (16/19) on one end and neurodevelopmental delay with severe hypotonia (3/19) on the other. Reversible or irreversible neurological decompensation after a febrile illness was common in the cohort, and there were invariable white matter abnormalities on neuroimaging. The study suggests that MMDS1 and HSP could be the two ends of the NFU1-related phenotypic continuum.