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J Am Soc Nephrol. 2016 Jun;27(6):1811-22. doi: 10.1681/ASN.2015050523. Epub 2015 Nov 13.

B Cell Reconstitution after Rituximab Treatment in Idiopathic Nephrotic Syndrome.

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Division of Nephrology and Dialysis,
Immunology Unit, Immunology and Pharmacotherapy Area.
Research Center, and.
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.
Clinical Epidemiology Unit, Medical Direction, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy; and.
Division of Nephrology and Dialysis.


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.


clinical immunology; glomerular disease; idiopathic nephrotic syndrome; immunosuppression; lymphocytes

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