BACKGROUND: About 10-20 % of children with idiopathic nephrotic syndrome (NS) are steroid-resistant (SR). Low expression of glucocorticoid receptors (GRs) has been associated with poor response to steroids in a variety of autoimmune diseases. This study was done to assess the expression of cytoplasmic GRs for CD3 and CD14 in children with NS. METHODS: Expression of cytoplasmic GRs in lymphocytes (CD3(+)/GR) and monocytes (CD14(+)/GR) in the peripheral blood were assessed in 51 children with NS before the start of therapy by flow cytometry. Patients were divided into two groups: 30 children who were steroid-sensitive (SSNS) and 21 children who had initial steroid resistance (SRNS). Twenty age- and sex-matched healthy children served as controls. RESULTS: Expression of CD3(+)/GR was significantly lower in SRNS in comparison to SSNS patients and controls (p < 0.0001). Similarly, expression of CD14(+)/GR was significantly lower in SRNS in comparison to SSNS patients (p < 0.0001) and controls (p = 0.002). CD3(+)/GR and CD14(+)/GR expression were not significantly different in SSNS patients compared with controls (p = 0.06 and 0.07 respectively). CONCLUSIONS: Patients with initial SRNS showed decreased GR expression in peripheral blood mononuclear cells (PBMC) before starting therapy, and this low expression may be one of the pathophysiological mechanisms of steroid resistance in these children.
BACKGROUND: About 10-20 % of children with idiopathic nephrotic syndrome (NS) are steroid-resistant (SR). Low expression of glucocorticoid receptors (GRs) has been associated with poor response to steroids in a variety of autoimmune diseases. This study was done to assess the expression of cytoplasmic GRs for CD3 and CD14 in children with NS. METHODS: Expression of cytoplasmic GRs in lymphocytes (CD3(+)/GR) and monocytes (CD14(+)/GR) in the peripheral blood were assessed in 51 children with NS before the start of therapy by flow cytometry. Patients were divided into two groups: 30 children who were steroid-sensitive (SSNS) and 21 children who had initial steroid resistance (SRNS). Twenty age- and sex-matched healthy children served as controls. RESULTS: Expression of CD3(+)/GR was significantly lower in SRNS in comparison to SSNS patients and controls (p < 0.0001). Similarly, expression of CD14(+)/GR was significantly lower in SRNS in comparison to SSNS patients (p < 0.0001) and controls (p = 0.002). CD3(+)/GR and CD14(+)/GR expression were not significantly different in SSNS patients compared with controls (p = 0.06 and 0.07 respectively). CONCLUSIONS:Patients with initial SRNS showed decreased GR expression in peripheral blood mononuclear cells (PBMC) before starting therapy, and this low expression may be one of the pathophysiological mechanisms of steroid resistance in these children.
Authors: D M Hurley; D Accili; C A Stratakis; M Karl; N Vamvakopoulos; E Rorer; K Constantine; S I Taylor; G P Chrousos Journal: J Clin Invest Date: 1991-02 Impact factor: 14.808
Authors: Lionel C Clement; Carmen Avila-Casado; Camille Macé; Elizabeth Soria; Winston W Bakker; Sander Kersten; Sumant S Chugh Journal: Nat Med Date: 2010-12-12 Impact factor: 53.440
Authors: Kim D Lu; Dan Cooper; Fadia Haddad; Frank Zaldivar; Monica Kraft; Shlomit Radom-Aizik Journal: Pediatr Res Date: 2017-06-21 Impact factor: 3.756