Stem cell mobilization in idiopathic steroid-sensitive nephrotic syndrome

Pediatr Nephrol. 2008 Aug;23(8):1251-6. doi: 10.1007/s00467-008-0793-2. Epub 2008 May 6.

Abstract

Steroid-sensitive nephrotic syndrome (SSNS) is classically thought to be a T-cell disorder. The aim of this study was to examine whether or not thymus homeostasis was affected in SSNS. Mature and naive T cell recent thymic emigrants were quantified in the peripheral blood of nephrotic patients and controls. Because the generation of new T cells by the thymus ultimately depends on hematopoietic stem cells, CD34+ cells were also included in the study. Nineteen patients with SSNS during relapse, 13 with SSNS during proteinuria remission, and 18 controls were studied. Cell-surface markers (CD3, CD4, CD8, CD19, CD16, CD56, CD45RA, CD62L, CD34, and CD38) were analyzed by flow cytometric analysis. T-cell rearrangement excision circles (TRECs) were quantified in CD2+ cells by real-time polymerase chain reaction. Stroma cell-derived factor-1 (SDF-1) genotype and metalloproteinase-9 (MMP-9) plasma levels were also determined. Mature T cells (CD4+ and CD8+), circulating naive T cells (CD62L+ and CD3+ CD62L+), and recent thymic emigrants (CD45RA+) as well as TRECs, that measure thymus production, had a similar level in the three groups of patients. Conversely, CD34+ hematopoietic stem cells displayed a two-fold increase in SSNS patients during relapse either compared with controls or SSNS patients at remission. In addition, compared with controls, SSNS patients at remission displayed (1) a decrease in CD19+ cells (B cells) and (2) an increase in CD16CD56+ cells [natural killer (NK) cells]. In conclusion, thymus homeostasis is not significantly affected in nephrotic patients. Hematopoietic stem-cell mobilization at proteinuria relapse, as well as changes in B and NK cells during remission, suggest that SSNS might be due to a general disturbance of hematopoietic and immune cell trafficking.

MeSH terms

  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • Child
  • Female
  • Flow Cytometry
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / immunology*
  • Humans
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology
  • Male
  • Nephrotic Syndrome / drug therapy
  • Nephrotic Syndrome / immunology*
  • Proteinuria / drug therapy
  • Proteinuria / immunology
  • Recurrence
  • Remission Induction
  • Steroids / therapeutic use
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology*

Substances

  • Steroids