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Stem cell mobilization in idiopathic steroid-sensitive nephrotic syndrome

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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.

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Acknowledgments

For their expert technical assistance, we especially thank Mir Moshasha, Christophe Raduget, Olivier Romagné, Hervé Rozenbaum, and Frédérique Siotto for flow cytometry, Marie-Noëlle Marson for SDF-1 genotyping, and Nadine Bonnin for G-CSF and MMP-9 immunoassays. Aurélie Bados kindly contributed to clinical data gathering. We are deeply indebted to Alain Doucet for helpful discussion and manuscript proofreading.

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Authors and Affiliations

  1. Laboratoire d’Hématologie, Hôpital Armand-Trousseau, Assistance Publique-Hôpitaux de Paris (APHP), 26 avenue du Docteur Arnold-Netter, 75571, Paris Cedex 12, France

    Hélène Lapillonne

  2. Unité INSERM U832, Université Pierre-et-Marie Curie, 27 rue de Chaligny, 75571, Paris Cedex 12, France

    Hélène Lapillonne

  3. Service de Néphrologie pédiatrique, Hôpital Robert-Debré, Assistance Publique-Hôpitaux de Paris (APHP), 48 boulevard Sérurier, 75935, Paris Cedex 19, France

    Annelaure Leclerc & Arnaud Garnier

  4. Service de Néphrologie Pédiatrique, Hôpital Armand-Trousseau, Assistance Publique-Hôpitaux de Paris (APHP), 26 avenue du Docteur Arnold-Netter, 75571, Paris Cedex 12, France

    Tim Ulinski & Georges Deschênes

  5. Service de Pédiatrie Générale, Hôpital Jean Verdier, Assistance Publique-Hôpitaux de Paris (APHP), Avenue du 14 Juillet, 93143, Bondy Cedex, France

    Laurent Balu

  6. SPI-BIO, CEA, DSV/iMETI/SIV, 18 route du Panorama, 92260 Fontenay-aux-Roses, France

    Nathalie Dereuddre-Bosquet

  7. Laboratoire d’Immunologie, Centre Hospitalier Régional et Universitaire de Tours, 2 bis boulevard Tonnelé, 37000, Tours, France

    Hervé Watier

  8. Unité de Biologie Cellulaire, Hôpital Saint-Louis, 1 avenue Claude-Vellefaux, 75475, Paris Cedex 10, France

    Marie-Hélène Schlageter

Authors
  1. Hélène Lapillonne
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  2. Annelaure Leclerc
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  3. Tim Ulinski
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  4. Laurent Balu
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  5. Arnaud Garnier
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  6. Nathalie Dereuddre-Bosquet
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  7. Hervé Watier
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  8. Marie-Hélène Schlageter
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  9. Georges Deschênes
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Correspondence to Georges Deschênes.

Additional information

Hélène Lapillonne and Annelaure Leclerc contributed equally to the paper.

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Lapillonne, H., Leclerc, A., Ulinski, T. et al. Stem cell mobilization in idiopathic steroid-sensitive nephrotic syndrome. Pediatr Nephrol 23, 1251–1256 (2008). https://doi.org/10.1007/s00467-008-0793-2

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  • DOI: https://doi.org/10.1007/s00467-008-0793-2

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