AUTHOR=Colucci Manuela , Riganati Martina , Zotta Federica , Gargiulo Antonio , Massella Laura , Ruggiero Barbara , Cotugno Nicola , Ricci Giulia , Palma Paolo , Emma Francesco , Vivarelli Marina 

TITLE=Prolonged impairment of immunological memory after anti-CD20 treatment in pediatric idiopathic nephrotic syndrome: an extended follow-up

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1736921

DOI=10.3389/fimmu.2025.1736921

ISSN=1664-3224

ABSTRACT=IntroductionAnti-CD20 therapy is an effective steroid-sparing option for pediatric idiopathic nephrotic syndrome (INS), but long-term data on immune reconstitution are limited.MethodsThirteen pediatric INS patients (7 males) were longitudinally evaluated at baseline, first long-term follow-up (mean 5.4 years), and extended follow-up (mean 6.6 years after the first follow-up, >3 years from the last anti-CD20 infusion). Clinical outcomes, B-cell subsets, serum immunoglobulin levels, vaccine competence, and infection rates were analyzed.ResultsAt the first follow-up, most patients had received one (n=6) or two (n=6) anti-CD20 courses; at the extended follow-up, five had undergone additional treatments. Four patients remained relapse-free during follow-up, whereas eight of nine who had previously relapsed continued to experience disease recurrence despite further anti-CD20 therapy. Oral immunosuppressant tapering improved: three patients were off therapy at first follow-up and six at the latest. Total, transitional and mature-naïve B cells reconstituted to normal ranges according to age over time. In contrast, total, IgM, and switched memory B cells remained significantly reduced (p<0.01). Patients in sustained remission exhibited lower switched memory B-cell counts than relapsing patients (p<0.05). Serum IgG levels increased at the extended follow-up, although six patients remained below normal. Four developed severe de novo hypogammaglobulinemia requiring long-term immunoglobulin replacement and showing increased infection susceptibility. Vaccine-specific IgG titers against tetanus and HBV remained below the limit of seroprotection despite re-immunization in most patients.ConclusionsAnti-CD20 therapy offers durable disease control and allows immunosuppressant reduction in pediatric INS, but persistent memory B-cell and humoral impairment warrant long-term immunologic monitoring.