title: Differential alteration in peripheral T-regulatory and T-effector cells with change in P-glycoprotein expression in Childhood Nephrotic Syndrome: A longitudinal study.
abstract: BACKGROUND
  Childhood Idiopathic Nephrotic Syndrome (INS) responds to glucocorticoid therapy, however, 60-80% of patients relapse and some of them become steroid non responsive. INS may occur because of T cell dysfunction, abnormal cytokines and podocytopathies which reverse on steroid treatment. The reason of relapses could be imbalances in T cells phenotypes and respective cytokines. Herein, we hypothesize that relapses in INS may occur due to imbalance in T-regulatory and T-effector cell with their respective cytokines and overexpression of P-gp on lymphocytes.
  
  
  METHODS
  The frequency of peripheral blood CD4(+)CD25(+)FoxP3(+) Treg, CD4(+)IFN-γ(+) Th1 and CD4(+)IL-4(+) Th2 lymphocytes and their respective cytokines and P-gp expression on peripheral blood lymphocytes (PBLs) were analyzed in INS patients at baseline (n=26), during remission (n=24) and at relapse (n=15).
  
  
  RESULTS
  Compared to baseline, the frequency of Tregs was significantly increased at remission and decreased during relapse. In contrast, the frequency of Th1 and Th2 lymphocytes was significantly decreased during remission and increased at the time of relapse. Similarly, expression of P-gp was significantly high at baseline and at the time of relapse as compared to remission. Levels of cytokines IL-10 and TGF-β in the supernatant of stimulated PBMCs was increased during remission and decreased during relapse. In contrast, levels of IFN-γ and IL-4 were decreased during remission and increased at the time of relapse.
  
  
  CONCLUSIONS
  Steroid therapy in INS induces decreased P-gp expression on PBLs along with increased frequency and cytokine response of T-regulatory cells, and reduced frequency and respective cytokine response of Th1 and Th2 cells during remission. However, reversal in the frequency and respective cytokines of T-regs, Th1 and Th2, and P-gp expression on PBLs occurs during relapses on follow-up.
authors: Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India. Electronic address: narayan.nephro@gmail.com.
authors: Narayan
authors: N
authors: Prasad
authors: Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors: Akhilesh K
authors: AK
authors: Jaiswal
authors: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors: Vikas
authors: V
authors: Agarwal
authors: Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors: Brijesh
authors: B
authors: Yadav
authors: Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors: Raj Kumar
authors: RK
authors: Sharma
authors: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors: Mohit
authors: M
authors: Rai
authors: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors: Harshit
authors: H
authors: Singh
authors: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors: Saurabh
authors: S
authors: Chaturvedi
authors: Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors: Ajay
authors: A
authors: Singh
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics*; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000276:immunology*; D012008:Recurrence; D012074:Remission Induction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000305:Adrenal Cortex Hormones; D016207:Cytokines; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: Effector T cells; Nephrotic Syndrome; P-gp expression; Regulatory T cells; Relapse