title: B Cell Reconstitution after Rituximab Treatment in Idiopathic Nephrotic Syndrome.
abstract: The pathogenesis of nephrotic syndrome is unclear. However, the efficacy of rituximab, a B cell-depleting antibody, in nephrotic syndrome suggests a pathogenic role of B cells. In this retrospective study, we determined by flow cytometry levels of B and T cell subpopulations before and after rituximab infusion in 28 pediatric patients with frequently relapsing or steroid-dependent nephrotic syndrome. At baseline, patients had lower median percentages of transitional and mature B cells than age-matched healthy controls (P<0.001). Rituximab induced full depletion of B cells (<1% of lymphocytes). At 1 year, most patients exhibited complete total and mature B cell recovery, whereas memory B cell subsets remained significantly depleted. Total T cell concentration did not change with rituximab, whereas the CD4(+)/CD8(+) T cell ratio tended to increase. Fourteen patients relapsed within 24 months, with a median follow-up of 11.2 months (interquartile range, 8-17.7 months). We observed no difference at baseline between nonrelapsing and relapsing patients in several clinical parameters and cell subset concentrations. Reconstitution of all memory B cell subpopulations, number of immunosuppressive drugs, and dose of tacrolimus during the last 4 months of follow-up were predictive of relapse in univariate Cox regression analysis. However, only delayed reconstitution of switched memory B cells, independent of immunosuppressive treatment, was protective against relapse in multivariate (P<0.01) and receiver operator characteristic (P<0.01 for percentage of lymphocytes; P=0.02 for absolute count) analyses. Evaluation of switched memory B cell recovery after rituximab may be useful for predicting relapse in patients with nephrotic syndrome.
authors.affiliation: Division of Nephrology and Dialysis, manuela.colucci@opbg.net.
authors.forename: Manuela
authors.initials: M
authors.lastname: Colucci
authors.affiliation: Immunology Unit, Immunology and Pharmacotherapy Area.
authors.forename: Rita
authors.initials: R
authors.lastname: Carsetti
authors.affiliation: Research Center, and.
authors.forename: Simona
authors.initials: S
authors.lastname: Cascioli
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico, Istituto di Ricerche Farmacologiche "Mario Negri," Clinical Research Center for Rare Diseases "Aldo e Cele Daccò," Ranica, Bergamo, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Casiraghi
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico, Istituto di Ricerche Farmacologiche "Mario Negri," Clinical Research Center for Rare Diseases "Aldo e Cele Daccò," Ranica, Bergamo, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Perna
authors.affiliation: Clinical Epidemiology Unit, Medical Direction, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy; and.
authors.forename: Lucilla
authors.initials: L
authors.lastname: Ravà
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico, Istituto di Ricerche Farmacologiche "Mario Negri," Clinical Research Center for Rare Diseases "Aldo e Cele Daccò," Ranica, Bergamo, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ruggiero
authors.affiliation: Division of Nephrology and Dialysis.
authors.forename: Francesco
authors.initials: F
authors.lastname: Emma
authors.affiliation: Division of Nephrology and Dialysis.
authors.forename: Marina
authors.initials: M
authors.lastname: Vivarelli
mesh_terms: D000293:Adolescent; D001402:B-Lymphocytes / Q000187:drug effects* / Q000502:physiology*; D002648:Child; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000276:immunology*; D012189:Retrospective Studies; D000069283:Rituximab / Q000494:pharmacology* / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology*
chemical_list: D007155:Immunologic Factors; D000069283:Rituximab
keywords: clinical immunology; glomerular disease; idiopathic nephrotic syndrome; immunosuppression; lymphocytes