Stem cell mobilization in idiopathic steroid-sensitive nephrotic syndrome.
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.
Lapillonne
Hélène
H
Laboratoire d'Hématologie, Hôpital Armand-Trousseau, Assistance Publique-Hôpitaux de Paris, 26 avenue du Docteur Arnold-Netter, 75571 Paris Cedex 12, France.
Leclerc
Annelaure
A
Ulinski
Tim
T
Balu
Laurent
L
Garnier
Arnaud
A
Dereuddre-Bosquet
Nathalie
N
Watier
Hervé
H
Schlageter
Marie-Hélène
MH
Deschênes
Georges
G
D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002648:Child; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000276:immunology*; D011507:Proteinuria / Q000188:drug therapy / Q000276:immunology; D012008:Recurrence; D012074:Remission Induction; D013256:Steroids / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D013256:Steroids