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B Cell Reconstitution after Rituximab Treatment in Idiopathic Nephrotic Syndrome

2015; American Society of Nephrology; Volume: 27; Issue: 6 Linguagem: Inglês

10.1681/asn.2015050523

1533-3450

Manuela Colucci, Rita Carsetti, Simona Cascioli, Federica Casiraghi, Annalisa Perna, Lucilla Ravà, Barbara Ruggiero, Francesco Emma, Marina Vivarelli,

Autoimmune Bullous Skin Diseases

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.