[go: up one dir, main page]
More Web Proxy on the site http://driver.im/ Skip to main content

Advertisement

Springer Nature Link
Log in

Stem cell mobilization in idiopathic steroid-sensitive nephrotic syndrome

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
£29.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (United Kingdom)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Eddy AA, Symons JM (2003) Nephrotic syndrome in childhood. Lancet 362:629–639

    Article  Google Scholar 

  2. Shalhoub RJ (1974) Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet 2:556–560

    Article  CAS  Google Scholar 

  3. Mansour H, Cheval L, Elalouf JM, Aude JC, Alyanakian MA, Mougenot B, Doucet A, Deschenes G (2005) T-cell transcriptome analysis points up a thymic disorder in idiopathic nephrotic syndrome. Kidney Int 67:2168–2177

    Article  CAS  Google Scholar 

  4. Lefrancois L (2006) Development, trafficking, and function of memory T-cell subsets. Immunol Rev 211:93–103

    Article  CAS  Google Scholar 

  5. Liu HH, Xie M, Schneider MD, Chen ZJ (2006) Essential role of TAK1 in thymocyte development and activation. Proc Natl Acad Sci U S A 103:11677–11682

    Article  CAS  Google Scholar 

  6. Voll RE, Jimi E, Phillips RJ, Barber DF, Rincon M, Hayday AC, Flavell RA, Ghosh S (2000) NF-kappa B activation by the pre-T cell receptor serves as a selective survival signal in T lymphocyte development. Immunity 13:677–689

    Article  CAS  Google Scholar 

  7. Barcena A, Galy AH, Punnonen J, Muench MO, Schols D, Roncarolo MG, de Vries JE, Spits H (1994) Lymphoid and myeloid differentiation of fetal liver CD34+ lineage cells in human thymic organ culture. J Exp Med 180:123–132

    Article  CAS  Google Scholar 

  8. Berard E, Broyer M, Dehennault M, Dumas R, Eckart P, Fischbach M, Loirat C, Martinat L (2005) Corticosensitive nephrotic syndrome (or nephrosis) in children. Therapeutic guideline proposed by the Pediatric Society of Nephrology. Nephrol Ther 1:150–156

    PubMed  Google Scholar 

  9. Benveniste O, Flahault A, Rollot F, Elbim C, Estaquier J, Pedron B, Duval X, Dereuddre-Bosquet N, Clayette P, Sterkers G, Simon A, Ameisen JC, Leport C (2005) Mechanisms involved in the low-level regeneration of CD4+ cells in HIV-1-infected patients receiving highly active antiretroviral therapy who have prolonged undetectable plasma viral loads. J Infect Dis 191:1670–1679

    Article  Google Scholar 

  10. Winkler C, Modi W, Smith MW, Nelson GW, Wu X, Carrington M, Dean M, Honjo T, Tashiro K, Yabe D, Buchbinder S, Vittinghoff E, Goedert JJ, O'Brien TR, Jacobson LP, Detels R, Donfield S, Willoughby A, Gomperts E, Vlahov D, Phair J, O'Brien SJ (1998) Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC). Science 279:389–393

    Article  CAS  Google Scholar 

  11. Shizuru JA, Negrin RS, Weissman IL (2005) Hematopoietic stem and progenitor cells: clinical and preclinical regeneration of the hematolymphoid system. Annu Rev Med 56:509–538

    Article  CAS  Google Scholar 

  12. Winkler IG, Levesque JP (2006) Mechanisms of hematopoietic stem cell mobilization: when innate immunity assails the cells that make blood and bone. Exp Hematol 34:996–1009

    Article  CAS  Google Scholar 

  13. McQuibban GA, Butler GS, Gong JH, Bendall L, Power C, Clark-Lewis I, Overall CM (2001) Matrix metalloproteinase activity inactivates the CXC chemokine stromal cell-derived factor-1. J Biol Chem 276:43503–43508

    Article  CAS  Google Scholar 

  14. Saito T, Usui N, Asai O, Dobashi N, Yano S, Osawa H, Takei Y, Takahara S, Ogasawara Y, Otsubo H, Yamaguchi Y, Minami J, Hoshi Y, Kataoka M, Aiba K (2007) Elevated serum levels of human matrix metalloproteinase-9 (MMP-9) during the induction of peripheral blood stem cell mobilization by granulocyte colony-stimulating factor (G-CSF). J Infect Chemother 13:426–428

    Article  CAS  Google Scholar 

  15. Akar H, Keven K, Celebi H, Orhan D, Nergizoglu G, Erbay B, Tulunay O, Ozcan M, Erturk S (2002) Nephrotic syndrome after allogeneic peripheral blood stem cell transplantation. J Nephrol 15:79–82

    PubMed  Google Scholar 

  16. Colombo AA, Rusconi C, Esposito C, Bernasconi P, Caldera D, Lazzarino M, Alessandrino EP (2006) Nephrotic syndrome after allogeneic hematopoietic stem cell transplantation as a late complication of chronic graft-versus-host disease. Transplantation 81:1087–1092

    Article  Google Scholar 

  17. Humphreys BD, Vanguri VK, Henderson J, Antin JH (2006) Minimal-change nephrotic syndrome in a hematopoietic stem-cell transplant recipient. Nat Clin Pract Nephrol 2:535–539 quiz 540.

    Article  Google Scholar 

  18. Nishimura M, Toki J, Sugiura K, Hashimoto F, Tomita T, Fujishima H, Hiramatsu Y, Nishioka N, Nagata N, Takahashi Y (1994) Focal segmental glomerular sclerosis, a type of intractable chronic glomerulonephritis, is a stem cell disorder. J Exp Med 179:1053–1058

    Article  CAS  Google Scholar 

  19. Sellier-Leclerc AL, Duval A, Riveron S, Macher MA, Deschenes G, Loirat C, Verpont MC, Peuchmaur M, Ronco P, Monteiro RC, Haddad E (2007) A humanized mouse model of idiopathic nephrotic syndrome suggests a pathogenic role for immature cells. J Am Soc Nephrol 18:2732–2739

    Article  Google Scholar 

  20. Hulton SA, Shah V, Byrne MR, Morgan G, Barratt TM, Dillon MJ (1994) Lymphocyte subpopulations, interleukin-2 and interleukin-2 receptor expression in childhood nephrotic syndrome. Pediatr Nephrol 8:135–139

    Article  CAS  Google Scholar 

  21. Lama G, Luongo I, Tirino G, Borriello A, Carangio C, Salsano ME (2002) T-lymphocyte populations and cytokines in childhood nephrotic syndrome. Am J Kidney Dis 39:958–965

    Article  CAS  Google Scholar 

  22. Andreau K, Lemaire C, Souvannavong V, Adam A (1998) Induction of apoptosis by dexamethasone in the B cell lineage. Immunopharmacology 40:67–76

    Article  CAS  Google Scholar 

  23. Lacki JK, Mackiewicz SH, Leszczynski P, Muller W (1997) The effect of intravenous cyclophosphamide pulse on peripheral blood lymphocytes in lupus erythematosus patients. Rheumatol Int 17:55–60

    Article  CAS  Google Scholar 

  24. Allison AC, Eugui EM (2000) Mycophenolate mofetil and its mechanisms of action. Immunopharmacology 47:85–118

    Article  CAS  Google Scholar 

  25. McChesney MB, Fujinami RS, Lampert PW, Oldstone MB (1986) Viruses disrupt functions of human lymphocytes II Measles virus suppresses antibody production by acting on B lymphocytes. J Exp Med 163:1331–1336

    Article  CAS  Google Scholar 

  26. Kuppers R, Schwering I, Brauninger A, Rajewsky K, Hansmann ML (2002) Biology of Hodgkin's lymphoma. Ann Oncol 13(Suppl 1):11–18

    Article  Google Scholar 

  27. Habib R, Girardin E, Gagnadoux MF, Hinglais N, Levy M, Broyer M (1988) Immunopathological findings in idiopathic nephrosis: clinical significance of glomerular “immune deposits”. Pediatr Nephrol 2:402–408

    Article  CAS  Google Scholar 

  28. Chen W, Wang HG, Srinivasula SM, Alnemri ES, Cooper NR (1999) B cell apoptosis triggered by antigen receptor ligation proceeds via a novel caspase-dependent pathway. J Immunol 163:2483–2491

    CAS  PubMed  Google Scholar 

  29. Kemper MJ, Meyer-Jark T, Lilova M, Muller-Wiefel DE (2003) Combined T- and B-cell activation in childhood steroid-sensitive nephrotic syndrome. Clin Nephrol 60:242–247

    Article  CAS  Google Scholar 

  30. Kemper MJ, Altrogge H, Ganschow R, Muller-Wiefel DE (2002) Serum levels of immunoglobulins and IgG subclasses in steroid sensitive nephrotic syndrome. Pediatr Nephrol 17:413–417

    Article  Google Scholar 

  31. Dantal J, Baatard R, Hourmant M, Cantarovich D, Buzelin F, Soulillou JP (1991) Recurrent nephrotic syndrome following renal transplantation in patients with focal glomerulosclerosis. A one-center study of plasma exchange effects. Transplantation 52:827–831

    CAS  PubMed  Google Scholar 

  32. Dantal J, Godfrin Y, Koll R, Perretto S, Naulet J, Bouhours JF, Soulillou JP (1998) Antihuman immunoglobulin affinity immunoadsorption strongly decreases proteinuria in patients with relapsing nephrotic syndrome. J Am Soc Nephrol 9:1709–1715

    CAS  PubMed  Google Scholar 

  33. Gilbert RD, Hulse E, Rigden S (2006) Rituximab therapy for steroid-dependent minimal change nephrotic syndrome. Pediatr Nephrol 21:1698–1700

    Article  Google Scholar 

Download references

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.

Author information

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
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Annelaure Leclerc
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tim Ulinski
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Laurent Balu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Arnaud Garnier
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nathalie Dereuddre-Bosquet
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hervé Watier
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Marie-Hélène Schlageter
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Georges Deschênes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Georges Deschênes.

Additional information

Hélène Lapillonne and Annelaure Leclerc contributed equally to the paper.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

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

Keywords

Search

Navigation