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Kidney Week

Abstract: FR-PO0835

Mycophenolate Mofetil Modulates Memory B Cells and Plasmablasts Without Persistent Impairment of Immunological Memory in Pediatric Steroid-Sensitive Nephrotic Syndrome

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Riganati, Martina, Ospedale Pediatrico Bambino Gesu IRCCS, Rome, Lazio, Italy
  • Zotta, Federica, Ospedale Pediatrico Bambino Gesu IRCCS, Rome, Lazio, Italy
  • Gargiulo, Antonio, Ospedale Pediatrico Bambino Gesu IRCCS, Rome, Lazio, Italy
  • Martelli, Giorgio, Ospedale Pediatrico Bambino Gesu IRCCS, Rome, Lazio, Italy
  • De Leo, Ester, Ospedale Pediatrico Bambino Gesu IRCCS, Rome, Lazio, Italy
  • Ricci, Giulia, Ospedale Pediatrico Bambino Gesu IRCCS, Rome, Lazio, Italy
  • Caridi, Gianluca, Istituto Giannina Gaslini, Genoa, Liguria, Italy
  • Kajana, Xhuliana, Istituto Giannina Gaslini, Genoa, Liguria, Italy
  • Angeletti, Andrea, Istituto Giannina Gaslini, Genoa, Liguria, Italy
  • Hengel, Felicitas E., Universitatsklinikum Hamburg-Eppendorf, Hamburg, HH, Germany
  • Tomas, Nicola M., Universitatsklinikum Hamburg-Eppendorf, Hamburg, HH, Germany
  • Huber, Tobias B., Universitatsklinikum Hamburg-Eppendorf, Hamburg, HH, Germany
  • Emma, Francesco, Ospedale Pediatrico Bambino Gesu IRCCS, Rome, Lazio, Italy
  • Vivarelli, Marina, Ospedale Pediatrico Bambino Gesu IRCCS, Rome, Lazio, Italy
  • Colucci, Manuela, Ospedale Pediatrico Bambino Gesu IRCCS, Rome, Lazio, Italy
Background

Despite the initial response to standard prednisone (PDN) therapy, children with steroid-sensitive nephrotic syndrome (SSNS) frequently experience relapses requiring intensified immunosuppression (IS), including repeated PDN cycles or second-line agents such as mycophenolate mofetil (MMF), calcineurin inhibitors (CNIs), or rituximab (RTX), which may induce prolonged impairment of humoral immunity. Data on the immunomodulatory effects of IS on pathogenic memory B cells, antibody-producing plasmablasts and anti-nephrin autoantibodies in SSNS are limited.

Methods

In this multicenter prospective study, a first cohort of patients with SSNS was enrolled since disease onset and followed for at least 12 months to evaluate the immunomodulatory effects of IS therapies. Significant results indicating differences in the effects of IS drugs on immune repertoire and competence were subsequently validated in an independent second cohort. Lymphocyte subsets were characterized by flow cytometry. Immune competence, vaccine responses, and autoantibody production were evaluated using Fluorospot, ELISA, and immunoprecipitation-Western blot.

Results

Patients with SSNS in the first cohort (n=34) were stratified according to maintenance therapy into four groups: no maintenance therapy, low-dose PDN, PDN+CNIs, and PDN+MMF. T-cell changes were minimal. Total, transitional, and naïve-mature B cells decreased after standard PDN and remained low regardless of maintenance therapy. In contrast, memory B cells and plasmablasts were significantly reduced only with PDN+MMF. Immune and vaccine responses were preserved with oral IS but not after RTX treatment. Similar findings were observed in an independent second cohort of patients with SSNS treated with MMF monotherapy (n=14) or RTX (n=14) and followed for 12-24 months. Anti-nephrin autoantibodies were detected in most patients at onset and declined after remission regardless of maintenance therapy.

Conclusion

Both MMF and RTX significantly reduced pathogenic B-cell subsets, whereas humoral immunity was impaired only with RTX.