B cell phenotype in pediatric idiopathic nephrotic syndrome
- 653 Downloads
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.
KeywordsNephrotic 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.
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.
- 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. https://doi.org/10.1126/scitranslmed.3008538 CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1016/j.jaut.2017.12.014 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1002/eji.201646574 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1681/ASN.2017111185 CrossRefGoogle Scholar
- 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). https://doi.org/10.1172/jci.insight.81836
- 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. https://doi.org/10.1038/s41390-018-0088-7