Pediatric Nephrology

, Volume 25, Issue 7, pp 1291–1298 | Cite as

Characterisation of renal immune cell infiltrates in children with nephrotic syndrome

  • Kerstin Benz
  • Maike Büttner
  • Katalin Dittrich
  • Valentina Campean
  • Jörg Dötsch
  • Kerstin Amann
Original Article


There is increasing evidence that not only T cells but also B cells may play an important role in the pathogenesis of idiopathic nephrotic syndrome (NS). We have evaluated the infiltrating immune cells found in renal biopsies from 38 children with NS using immunohistochemistry techniques involving antibodies against T cells (CD3, CD4, CD8, FoxP3), B cells (CD20), macrophages (CD68) and follicular dendritic cells (CD21). Kidney biopsies with thin basement membrane disease were used as controls. We found higher numbers of interstitial CD3-positive T cells and macrophages in patients with focal segmental glomerulosclerosis (FSGS) than in those with minimal change glomerulopathy (MCGN) and in the controls, and significantly lower FoxP3-positive cells in patients with FSGS, MCGN and steroid-dependent NS than in the controls. Significantly higher numbers of glomerular B cells were found in FSGN patients than in MCGN patients and controls. Of note, in three patients who were later successfully treated with anti-CD20 antibody rituximab, the number of renal B cells was negligible in the preceding biopsy. In conclusion, the higher numbers of interstitial CD3-positive T cells in renal biopsies of pediatric patients with FSGS argue for a higher inflammatory activity. The significantly higher number of glomerular B cells in FSGS patients may indicate a particular pathogenetic role or epiphenomenon in this disease. However, patients with no interstitial or glomerular B cells could also benefit from rituximab treatment.


B-lymphocyte Idiopathic nephrotic syndrome Macrophage Renal infiltration T-lymphocyte 



The study was supported by the IZKF (Interdisziplinäres Zentrum für Klinische Forschung) Erlangen to K. B. and by the Deutsche Forschungsgemeinschaft (SFB 423, Z2, B13). The authors especially thank Miriam Reutelshöfer, Claudia Störer and Christa Winkelmann for expert technical assistance.


  1. 1.
    Shalhoub RJ (1974) Pathogenesis of lipoid nephrosis. A disorder of T-cell function. Lancet 2:556–560CrossRefPubMedGoogle Scholar
  2. 2.
    Lin CY, Lee BH, Lin CC, Chen WP (1990) A study of the relationship between childhood nephrotic syndrome and allergic diseases. Chest 97:1408–1411CrossRefPubMedGoogle Scholar
  3. 3.
    Groshong T, Mendelson L, Mendoza S, Bazaral M, Hamburger R, Tune B (1973) Serum IgE in patients with minimal change nephrotic syndrome. J Pediatr 83:767–771CrossRefPubMedGoogle Scholar
  4. 4.
    Van den Berg JG, Weening JJ (2004) Role of the immune system in the pathogenesis of idiopathic nephrotic syndrome. Clin Sci (Lond) 107:125–136CrossRefGoogle Scholar
  5. 5.
    Koyama A, Fujisaki M, Kobayashi M, Igarashi M, Narita M (1991) A glomerular permeability factor produced by human T-cell hybridomas. Kidney Int 40:453–460CrossRefPubMedGoogle Scholar
  6. 6.
    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 39:958–965CrossRefPubMedGoogle Scholar
  7. 7.
    Dötsch J, Müller-Wiefel DE, Kemper MJ (2008) Rituximab: is replacement of cyclophosphamide and calcineurin inhibitors in steroid-dependent nephrotic syndrome possible? Pediatr Nephrol 23:3–7CrossRefPubMedGoogle Scholar
  8. 8.
    Wada T, Pippin JW, Marshall CB, Griffin SV, Shankland SJ (2005) Dexamethasone prevents podocyte apoptosis induced by puromycin aminonucleoside: role of p53 and bcl-2-related family proteins. J Am Soc Nephrol 16:2615–2625CrossRefPubMedGoogle Scholar
  9. 9.
    Mathieson PW (2008) Proteinuria and immunity-an overstated relationship? N Engl J Med 359:2492–2494CrossRefPubMedGoogle Scholar
  10. 10.
    Benz K, Dötsch J, Rascher W, Stachel D (2004) Change of the course of steroid-dependent nephrotic syndrome after rituximab therapy. Pediatr Nephrol 19:794–797CrossRefPubMedGoogle Scholar
  11. 11.
    Gilbert RD, Hulse E, Rigden S (2006) Rituximab therapy for steroid-dependent minimal change nephrotic syndrome. Pediatr Nephrol 21:1698–1700CrossRefPubMedGoogle Scholar
  12. 12.
    Guigonis V, Dallocchio A, Baudouin V, Dehennault M, Hachon-Le Camus C, Afanetti M, Groothoff J, Llanas B, Niaudet P, Nivet H, Raynaud N, Tague S, Ronco P, Bouissou F (2008) Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases. Pediatr Nephrol 23:1269–1279CrossRefPubMedGoogle Scholar
  13. 13.
    Arbeitsgemeinschaft für Pädiatrische Nephrologie (APN) (1981) Alternate-day prednisone is more effective than intermittent prednisone in frequently relapsing nephrotic syndrome. Eur J Pediatr 135:229–237CrossRefGoogle Scholar
  14. 14.
    Frank K, Zeier M, Gross ML, Waldherr R, Ritz E, Amann K (2006) Comprehensive immunohistological analysis of the endothelin system in human kidney grafts. Nephrol Dial Transplant 21:1365–1372CrossRefPubMedGoogle Scholar
  15. 15.
    Kemper MJ, Zepf K, Klaassen I, Link A, Müller-Wiefel DE (2005) Changes of lymphocyte populations in pediatric steroid-sensitive nephrotic syndrome are more pronounced in remission than in relapse. Am J Nephrol 25:132–137CrossRefPubMedGoogle Scholar
  16. 16.
    Sahali D, Pawlak A, Le Gouvello S, Lang P, Valanciute A, Remy P, Loirat C, Niaudet P, Benson A, Guellaen G (2001) Transcriptional and post-transcriptional alterations of NFkB-alpha in active minimal change nephrotic syndrome. J Am Soc Nephrol 12:1648–1658PubMedGoogle Scholar
  17. 17.
    Kimata H, Fujimoto M, Furusho K (1995) Involvement of interleukin (IL)-13, but not IL-4 in spontaneous IgE and IgG4 production in nephrotic syndrome. Eur J Immunol 25:1497–1501CrossRefPubMedGoogle Scholar
  18. 18.
    Shao XS, Yang XQ, Zhao XD, Li Q, Xie YY, Wang XG, Wang M, Zhang W (2009) The prevalence of Th17 cells and FOXP3 regulate T-cells (Treg) in children with primary nephrotic syndrome. Pediatr Nephrol 24:1683–1690CrossRefPubMedGoogle Scholar
  19. 19.
    Frank C, Herrmann M, Fernandez S, Dirnecker D, Böswald M, Kolowos W, Ruder H, Haas JP (2000) Dominant T-cells in idiopathic nephrotic syndrome of childhood. Kidney Int 57:510–517CrossRefPubMedGoogle Scholar
  20. 20.
    Andre S, Tough DF, Lacroix-Desmazes S, Kaveri SV, Bayry J (2009) Surveillance of antigen-presenting cells by CD4+ CD35+ regulatory T-cells in autoimmunity: immunopathogenesis and therapeutic implications. Am J Pathol 174:1575–1587CrossRefPubMedGoogle Scholar
  21. 21.
    Mahajan D, Wang Y, Qin X, Wang Y, Zheng G, Wang YM, Alexander SI, Harris DC (2006) CD4+CD25+ regulatory T-cells protect against injury in an innate murine model of chronic kidney disease. J Am Soc Nephrol 17:2731–2741CrossRefPubMedGoogle Scholar
  22. 22.
    Le Berre L, Bruneau S, Naulet J, Renaudin K, Buzelin F, Usal C, Snit H, Condamine T, Soulilou JP, Dantal J (2009) Induction of T regulatory cells attenuates idiopathic nephrotic syndrome. J Am Soc Nephrol 20:57–67CrossRefPubMedGoogle Scholar
  23. 23.
    Bagga A, Sinha A, Moudgil A (2007) Rituximab in patients with the steroid-resistant nephrotic syndrome. N Engl J Med 356:2751–2752CrossRefPubMedGoogle Scholar
  24. 24.
    Kemper MJ, Meyer-Jark T, Lilova M, Müller-Wiefel DE (2003) Combined T- and B-cell activation in childhood steroid sensitive nephrotic syndrome. Clin Nephrol 60:242–247PubMedGoogle Scholar
  25. 25.
    Yabu JM, Ho B, Scandling JD, Vincenti F (2008) Rituximab failed to improve nephrotic syndrome in renal transplant patients with recurrent focal segmental glomerulosclerosis. Am J Transplant 8:222–227PubMedGoogle Scholar
  26. 26.
    Remuzzi G, Chiurchiu C, Abbate M, Brusegan V, Bontempelli M, Ruggenenti P (2002) Rituximab for idiopathic membranous nephropathy. Lancet 360:923–924CrossRefPubMedGoogle Scholar
  27. 27.
    Fervenza FC, Cosio FG, Erickson SB, Specks U, Herzenberg AM, Dillon JJ, Leung N, Cohen IM, Wochos DN, Bergstralh E, Hladunewich M, Cattran DC (2008) Rituximab treatment of idiopathic membranous nephropathy. Kidney Int 73:117–125CrossRefPubMedGoogle Scholar
  28. 28.
    Cohen CD, Calvaresi N, Armelloni S, Schmid H, Henger A, Ott U, Rastaldi MP, Kretzler M (2005) CD 20 positive infiltrates in human membranous glomerulonephritis. J Nephrol 18:328–333PubMedGoogle Scholar
  29. 29.
    Sarwal M, Chua MS, Kambham N, Hsieh SC, Satterwhite T, Masek M, Salvatierra O Jr (2003) Molecular heterogeneity in acute renal allograft rejection identified by DNA microarray profiling. N Engl J Med 349:125–138CrossRefPubMedGoogle Scholar
  30. 30.
    Scheepstra C, Bemelman FJ, van der Loos C, Rowshani AT, van Donselaar-Van der Pant KA, Idu MM, ten Berge IJ, Florquin S (2008) B-cells in cluster or in a scattered pattern do not correlate with clinical outcome of renal allograft rejection. Transplantation 27:772–778CrossRefGoogle Scholar
  31. 31.
    Hotta O, Yusa N, Kitamura H, Taguma Y (2000) Urinary macrophages as activity markers of renal injury. Clin Chim Acta 297:123–133CrossRefPubMedGoogle Scholar

Copyright information

© IPNA 2010

Authors and Affiliations

  • Kerstin Benz
    • 1
    • 2
  • Maike Büttner
    • 2
  • Katalin Dittrich
    • 1
  • Valentina Campean
    • 2
  • Jörg Dötsch
    • 1
  • Kerstin Amann
    • 2
  1. 1.Klinik für Kinder und JugendlicheFriedrich-Alexander-Universität Erlangen–NürnbergErlangenGermany
  2. 2.Pathologisches Institut ErlangenFriedrich-Alexander-Universität Erlangen–NürnbergErlangenGermany

Personalised recommendations