Fas-induced apoptosis in malnourished infants

Background: Malnutrition in children is frequently associated with an increased incidence of infection. Apoptosis of immune cells in undernourished organisms may cause an increase in the organism's susceptibility to diseases related to immune suppression. Lymphocyte apoptosis was described in malnutrition. The role of factor of apoptosis signal (fas,CD95) in apoptosis of lymphocyte populations in malnourished children is still unclear. Objective: This study investigated apoptosis in T lymphocytes in different types of malnutrition and the role of Fas in lymphocyte apoptosis and its relation to clinical and laboratory parameters of malnutrition. Study design: Sixty-three malnourished infants and children were compared to 27 healthy controls. Beside thorough history and clinical examination, laboratory investigations and flow cytometry assessment of T lymphocytes were done. The viability of T lymphocytes was determined by combination of fluorescence dye 7-amino actinomycin, CD95 and CD3. Results: There was significant increase in apoptotic T-cells in the patients compared to the controls. There was up-regulation of Fas expression in CD3+ cells. Furthermore CD3+/CD95+ cells were less viable than CD3+/CD95- cells of the patients and than CD3+/CD95+ cells of the controls. All the clinical and laboratory parameters of the studied patients showed no significant correlations with any of the apoptotic indices. Conclusion: Increased apoptosis in T lymphocytes in malnourished children may be the cause of the decrease in lymphocyte count in their peripheral blood. This in turn may be the cause of decreased cell mediated immunity and the more common occurrence of infection in such patients. Upregulation of Fas may be the cause of apoptosis in T lymphocytes in these malnourished children.Keywords: Fas, apoptosis, malnutrition, flow cytometry, infection, T lymphocytes.Egypt J Pediatr Allergy Immunol 2010;8(1):27-3

Clinical and genetic assessment of pediatric patients with Gaucher’s disease in Upper Egypt

Background: Gaucher’s disease (GD) is an autosomal recessive genetic disorder that results from pathogenic mutations of GBA gene encoding the enzyme glucocerebrosidase (acid b-glucosidase). Of the approximately 300 mutations associated with GD, 4 accounts for the majority of mutations seen in GD patients: N370S, L444P, 84 GG and IVS2+1.Aim: Establishing and providing, clinical and molecular backgrounds of pediatric patients with GD in Upper Egypt.Subjects and methods: The present study is a cross sectional study, carried out on 26 pediatric patients with GD. They were recruited from the pediatric outpatient clinics and inpatients Pediatric departments of Assiut and Qena University hospitals, Upper Egypt. Clinical evaluation and mutation analysis using commercially available strip assay kit after PCR amplification of the target gene were done for all included GD patients.Results: Consanguinity between patients’ parents was present in 73.1% of the included patients. 76.9% of included patients were of type 1 GD, while 23.1% were of type 3 GD and none of our patients was classified as type 2 GD. The main frequent clinical presentations of GD in this study were hepatosplenomegaly (88.5%); pallor (76.9%); abdominal distension (61.5%) and musculoskeletal involvement (37.1%). Neurological abnormalities of type 3 GD included in this study were squint, seizures and delayed mental development. Five different genotypes were detected, homozygous for the mutation L444P, homozygous for the mutation N370S, heterozygous for the mutations N370S and rec Ncil, heterozygous for IVS2 +1 and rec NciI, heterozygous for L444P and IVS2 +1. Conclusions: Non-neuropathic type 1 and type 3 GD were the only clinical types found in the present study. The most common mutant alleles found in this study were L444P and N370S

Upregulation of CD146 in Pediatric B-Cell Acute Lymphocytic Leukemia and Its Implications on Treatment Outcomes

Background and Aim. We studied through flow cytometry the expression of CD146 on different T cells, and B-cell ALL blasts trying to correlate its expression with different prognostic factors of B-cell ALL and treatment outcomes. Patients and Methods. All pediatric patients with B-cell ALL were subjected to bone marrow examination and cytochemistry, flow cytometric immunophenotyping using monoclonal antibodies utilized for diagnosis of B-ALL including CD34, CD19, CD10, CD22, and intracellular IgM. The diagnosis was based on standard morphologic, cytochemical, and immunophenotypic followed by flow cytometric detection of CD146 expression on blast cells, CD4+, and CD8+ T cells. Results. Significant accumulations of CD146+CD4+ cells, CD146+CD8+ cells, CD4+, CD8+, and lymphocytes in patients were compared to controls, the mean percentages of CD146+CD4+ cells, CD146+CD8+ cells, and CD146+ blasts were significantly higher in patients than controls, and in addition, these cells were associated with poor overall survival and disease-free survival. The median OS for patients with complete response was 22±1.633 (95%CI=18.799‐25.201), while for those without complete response, it was 13±3.928 (95%CI=5.301‐25.699), with log‐rank=5.71, P=0.017. Conclusion. CD146 was expressed significantly in children’s B-ALL and associated with poor prognostic features including poor response and treatment outcomes and could be a possible poor prognostic factor in pediatric B-cell ALL

High dose dexamethasone as an alternative rescue therapy for active bleeding in children with chronic ITP: clinical and immunological effects

High-dose dexamethasone (HD-DXM) is debated as a second-line therapy for chronic Immune thrombocytopenia (ITP) in children. The aim of this study is to evaluate the efficacy and safety of HD-DXM as an emergency therapy in uncontrolled bleeding in children with chronic ITP and to assess its immunological effect on dendritic cells (DCs) percentage and their co-stimulatory markers CD86 and CD83. Totally, 20 children previously diagnosed as chronic ITP were enrolled in this study and all admitted to hospital with uncontrolled bleeding. Patients received HD-DXM as a single daily dose for 4 days. Blood samples were withdrawn from patients just prior to HD-DXM therapy and on day 5 to evaluate the platelet count and for flowcytometric analysis of DCs. Daily assessment of bleeding severity was performed. The platelet counts significantly increased in patients after 5 days of initiation of therapy compared with platelet count before therapy (p-value = 0. 0002). Control of bleeding observed in (90%), complete response (CR) documented in (50%), response (R) documented in (40%), and no response (NR) documented in (10%) of patients. The time to respond was raging from 1 to 3 days and minor complication recorded in two patients. Both plasmacytoid DCs and myeloid DCs percentage and their expression of co-stimulatory markers, CD86 and CD83 decreased significantly after HD-DXM therapy. Conclusion: short course of HD-DXM as a rescue therapy seems to be an effective alternative emergency treatment for uncontrolled bleeding in chronic ITP children especially in nations with limited resources

Effects of royal jelly supplementation on regulatory T cells in children with SLE

Background and objective: To our knowledge, no previous studies have focused on the immunomodulatory effects of fresh royal jelly (RJ) administration on systemic lupus erythematosus (SLE) in humans. Our aim was to study the effect of fresh RJ administration on the disease course in children with SLE with some immunological markers (CD4+ and CD8+ regulatory T cells and T lymphocytes apoptosis). Methods: This was an open-label study in which 20 SLE children received 2 g of freshly prepared RJ daily, for 12 weeks. Results: The percentages of CD4+ CD25+high FOXP3+cells (CD4+ regulatory T cells) and CD8+CD25+high FOXP3+cells (CD8+ regulatory T cells) were significantly increased after RJ treatment when compared with baseline values. Apoptotic CD4 T lymphocytes were significantly decreased after RJ therapy when compared with baseline values and the control group. Conclusion: This is the first human study on the effect of RJ supplementation in children with SLE. Our results showed improvements with 3-month RJ treatment with regard to the clinical severity score and laboratory markers for the disease. At this stage, it is a single study with a small number of patients, and a great deal of additional wide-scale randomized controlled studies are needed to critically validate the efficacy of RJ in SLE