الفهرس 
Overview of Sickle Cell DiseaseOnly 14 pages are availabe for public view
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Abstract
Background: Sickle cell disease (SCD) is increasingly appreciated as an inflammatory condition associated with alterations in immune phenotype and function. CD4+ T lymphocyte influence the functions of virtually all other cells of the immune system, including other T cells, B cells, macrophages and natural killer (NK) cells. CD4+CD28null T-cells are a subset of long-lived directly cytotoxic CD4+ T lymphocytes that have pro-inflammatory functions characterized by the production of high levels of interferon-gamma (IFN-gamma). Aim: To assess the percentage of CD4+CD28null T cells as well as IFN-gamma levels in 40 children and adolescents with SCD compared with 40 age- and sex-matched healthy controls and evaluate their relation to hemolysis, iron overload, vaso-occlusive crisis (>3 attacks/year) and response to therapy. Methods: SCD patients in steady state were studied focusing on history of frequent vaso-occlusive crisis, transfusion history, hydroxyurea therapy, hematological profile and serum ferritin. Analysis of T cells was done by flow cytometry for assessment of CD4+ T lymphocytes and CD4+CD28null T-cells. Serum levels of interferon-gamma were assessed by enzyme linked immunosorbent assay (ELISA). Results: Patients with SCD had higher WBCs and lower hemoglobin level compared with controls. CD4+ T lymphocytes, CD4+CD28null T-cells and IFN-gamma levels were significantly higher in patients than in controls. Patients with history of frequent sickling crisis had higher percentage of CD4+CD28null T-cells and IFN-gamma than those without. The levels of these cells and IFN-gamma were significantly lower among hydroxyurea-treated patients as well as those on combined chelation and hydroxyurea therapy. There were significant positive correlations between each of CD4+ T lymphocytes and CD4+CD28null T-cells and transfusion index and iron overload per day. Moreover, CD4+CD28null T-cells were positively correlated to IFN-gamma while negatively correlated to cardiac T2* and duration of hydroxyurea therapy. A significant positive correlation was found between IFN-gamma and CD4+CD28null T-cells while it was negatively correlated to cardiac T2* and duration of hydroxyurea. Conclusions: Expression of CD4+CD28null T-cells with increased production IFN-gamma highlights the role of immune dysfunction in pediatric patients with SCD. Alteration of this subset of T lymhocytes is related to increased iron overload and higher incidence of vaso-occlusive crisis. Hydroxyurea and/or iron chelation therapy significantly contributes to the normalization of cytotoxic lymphocytes and attenuates immune dysfunction.