B Cell Reconstitution after Rituximab Treatment in Idiopathic Nephrotic Syndrome

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

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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.

Original languageEnglish
Pages (from-to)1811-1822
JournalJournal of the American Society of Nephrology : JASN
Volume27
Issue number6
DOIs
Publication statusPublished - 2016

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B-Lymphocytes
Nephrotic Syndrome
Therapeutics
Immunosuppressive Agents
T-Lymphocytes
Recurrence
Lymphocytes
B-Lymphocyte Subsets
B-Lymphoid Precursor Cells
Rituximab
Congenital Nephrosis
Tacrolimus
Flow Cytometry
Retrospective Studies
Cell Count
Steroids
Regression Analysis
Pediatrics
Antibodies
Pharmaceutical Preparations

Keywords

  • Journal Article

Cite this

B Cell Reconstitution after Rituximab Treatment in Idiopathic Nephrotic Syndrome. / Colucci, Manuela; Carsetti, Rita; Cascioli, Simona; Casiraghi, Federica; Perna, Annalisa; Ravà, Lucilla; Ruggiero, Barbara; Emma, Francesco; Vivarelli, Marina.

In: Journal of the American Society of Nephrology : JASN, Vol. 27, No. 6, 2016, p. 1811-1822.

Research output: Contribution to journalArticle

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AU - Vivarelli, Marina

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