Pediatric Nephrology

, Volume 34, Issue 1, pp 177–181 | Cite as

B cell phenotype in pediatric idiopathic nephrotic syndrome

  • Manuela ColucciEmail author
  • Rita Carsetti
  • Simona Cascioli
  • Jessica Serafinelli
  • Francesco Emma
  • Marina Vivarelli
Brief Report



A pathogenic role of B cells in non-genetic nephrotic syndrome has been suggested by the efficacy of rituximab, a B cell depleting antibody, in maintaining a prolonged remission. However, little information is available on B cell homeostasis in nephrotic syndrome patients.


We retrospectively analyzed by flow cytometry the distribution of different B cell subpopulations in 107 steroid-sensitive and in 6 genetic steroid-resistant nephrotic syndrome pediatric patients, compared with age- and sex-matched controls.


Fifty-one steroid-sensitive patients at disease onset, before starting immunosuppression, presented significantly increased levels of total, transitional, memory, and switched memory B cells compared to controls. Oral immunosuppression strongly affected transitional and mature B cell levels in 27 patients in relapse and also in 29 patients in remission, whereas memory B cells were significantly higher compared to controls during relapse, despite the immunosuppressive treatment, and were normalized only in patients in remission. Children with genetic forms of steroid-resistant nephrotic syndrome presented no differences in B cell profile from controls.


Our study indicates that memory B cells, more than other B cell subsets, are increased and appear to be pathogenically relevant in steroid-sensitive nephrotic syndrome pediatric patients.


Nephrotic syndrome Children B cells Immunosuppressive treatment 



M.C. and M.V. were supported by Associazione per la Cura del Bambino Nefropatico-Onlus and Ricerca Corrente of the Italian Ministry of Health.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Supplementary material

467_2018_4095_MOESM1_ESM.docx (20 kb)
Supplementary Table 1 (DOCX 20 kb)
467_2018_4095_MOESM2_ESM.jpg (766 kb)
Supplementary Figure 1. Gating strategy to discriminate the different B cell subpopulations by multicolor flow cytometry analysis. (JPG 766 kb)
467_2018_4095_MOESM3_ESM.jpg (486 kb)
Supplementary Figure 2. Analysis of circulating B cell subpopulations in pediatric steroid-sensitive nephrotic syndrome. Levels of B-cell subsets, expressed as cells/μl of blood, from patients at disease onset (n=51), in relapse (n=27) or in remission (n=29). (A) Gated total CD19+ B cells were identified based on the expression of surface markers as depicted in Fig. S1: (B) transitional, (C) mature, (D) memory, (E) IgM memory, and (F) switched memory B cells. Each box plot represents the median and the 25th and 75th centiles. Error bars represent the smallest and the largest values. Differences between groups were compared using the nonparametric Kruskal-Wallis test and, if significant, unpaired Mann-Whitney U test was applied. *, p<0.05; **, p<0.01; ***, p<0.001. (JPG 485kb)
467_2018_4095_MOESM4_ESM.jpg (573 kb)
Supplementary Figure 3. Multicolor flow cytometry analysis of circulating B-cell subpopulations in children with genetic forms of steroid-resistant nephrotic syndrome. Levels of B-cell subsets from patients with genetic forms of steroid-resistant nephrotic syndrome (n=6) were compared with values of the same number of age- and sex-matched healthy donors (HD). (A) Gated total CD19+ B cells were identified on the basis of the expression of surface markers as depicted in Fig. S1; (B) transitional, (C) mature, (D) total memory, (E) IgM memory, and (F) switched memory B cells were expressed as percentages of total lymphocytes. Each box plot represents the median and the 25th and 75th centiles. Error bars represent the smallest and the largest values. Differences between groups were compared using the nonparametric unpaired Mann-Whitney U test. (JPG 572kb)


  1. 1.
    Colucci M, Corpetti G, Emma F, Vivarelli M (2018) Immunology of idiopathic nephrotic syndrome. Pediatr Nephrol 33:573–584. CrossRefPubMedGoogle Scholar
  2. 2.
    Vivarelli M, Massella L, Ruggiero B, Emma F (2017) Minimal change disease. Clin J Am Soc Nephrol 12:332–345. CrossRefPubMedGoogle Scholar
  3. 3.
    Ravani P, Bonanni A, Rossi R, Caridi G, Ghiggeri GM (2016) Anti-CD20 antibodies for idiopathic nephrotic syndrome in children. Clin J Am Soc Nephrol 11:710–720. CrossRefPubMedGoogle Scholar
  4. 4.
    Delville M, Sigdel TK, Wei C, Li J, Hsieh SC, Fornoni A, Burke GW, Bruneval P, Naesens M, Jackson A, Alachkar N, Canaud G, Legendre C, Anglicheau D, Reiser J, Sarwal MM (2014) A circulating antibody panel for pretransplant prediction of FSGS recurrence after kidney transplantation. Sci Transl Med 6:256ra136. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Jamin A, Berthelot L, Couderc A, Chemouny JM, Boedec E, Dehoux L, Abbad L, Dossier C, Daugas E, Monteiro RC, Deschenes G (2018) Autoantibodies against podocytic UCHL1 are associated with idiopathic nephrotic syndrome relapses and induce proteinuria in mice. J Autoimmun 89:149–161. CrossRefPubMedGoogle Scholar
  6. 6.
    Printza N, Papachristou F, Tzimouli V, Taparkou A, Kanakoudi-Tsakalidou F (2009) Peripheral CD19+ B cells are increased in children with active steroid-sensitive nephrotic syndrome. NDT Plus 2:435–436. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Marasco E, Farroni C, Cascioli S, Marcellini V, Scarsella M, Giorda E, Piano Mortari E, Leonardi L, Scarselli A, Valentini D, Cancrini C, Duse M, Grimsholm O, Carsetti R (2017) B-cell activation with CD40L or CpG measures the function of B-cell subsets and identifies specific defects in immunodeficient patients. Eur J Immunol 47:131–143. CrossRefPubMedGoogle Scholar
  8. 8.
    Colucci M, Carsetti R, Cascioli S, Casiraghi F, Perna A, Rava L, Ruggiero B, Emma F, Vivarelli M (2016) B cell reconstitution after rituximab treatment in idiopathic nephrotic syndrome. J Am Soc Nephrol 27:1811–1822. CrossRefPubMedGoogle Scholar
  9. 9.
    Lapillonne H, Leclerc A, Ulinski T, Balu L, Garnier A, Dereuddre-Bosquet N, Watier H, Schlageter MH, Deschenes G (2008) Stem cell mobilization in idiopathic steroid-sensitive nephrotic syndrome. Pediatr Nephrol 23:1251–1256. CrossRefPubMedGoogle Scholar
  10. 10.
    Basu B, Sander A, Roy B, Preussler S, Barua S, Mahapatra TKS, Schaefer F (2018) Efficacy of rituximab vs tacrolimus in pediatric corticosteroid-dependent nephrotic syndrome: a randomized clinical trial. JAMA Pediatr. CrossRefGoogle Scholar
  11. 11.
    Hoffman W, Lakkis FG, Chalasani G (2016) B cells, antibodies, and more. Clin J Am Soc Nephrol 11:137–154. CrossRefPubMedGoogle Scholar
  12. 12.
    Debiec H, Dossier C, Letouze E, Gillies CE, Vivarelli M, Putler RK, Ars E, Jacqz-Aigrain E, Elie V, Colucci M, Debette S, Amouyel P, Elalaoui SC, Sefiani A, Dubois V, Simon T, Kretzler M, Ballarin J, Emma F, Sampson MG, Deschenes G, Ronco P (2018) Transethnic, genome-wide analysis reveals immune-related risk alleles and phenotypic correlates in pediatric steroid-sensitive nephrotic syndrome. J Am Soc Nephrol. CrossRefGoogle Scholar
  13. 13.
    Kim AH, Chung JJ, Akilesh S, Koziell A, Jain S, Hodgin JB, Miller MJ, Stappenbeck TS, Miner JH, Shaw AS (2017) B cell-derived IL-4 acts on podocytes to induce proteinuria and foot process effacement. JCI Insight 2(21).
  14. 14.
    Good KL, Avery DT, Tangye SG (2009) Resting human memory B cells are intrinsically programmed for enhanced survival and responsiveness to diverse stimuli compared to naive B cells. J Immunol 182:890–901CrossRefGoogle Scholar
  15. 15.
    Bhatia D, Sinha A, Hari P, Sopory S, Saini S, Puraswani M, Saini H, Mitra DK, Bagga A (2018) Rituximab modulates T- and B-lymphocyte subsets and urinary CD80 excretion in patients with steroid-dependent nephrotic syndrome. Pediatr Res.

Copyright information

© IPNA 2018

Authors and Affiliations

  1. 1.Laboratory of Nephrology, Department of Rare DiseasesIRCCS Ospedale Pediatrico Bambino GesùRomeItaly
  2. 2.Department of Laboratories, Immunology Research Area - Unit of Diagnostic Immunology, Unit of B-cell PathophysiologyIRCCS Ospedale Pediatrico Bambino GesùRomeItaly
  3. 3.Division of Nephrology, Department of Pediatric SubspecialtiesIRCCS Ospedale Pediatrico Bambino GesùRomeItaly

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