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Anti-rituximab antibodies in pediatric steroid-dependent nephrotic syndrome

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Abstract

Background

Rituximab is a chimeric anti-CD20 monoclonal antibody that induces sustained remission in children with steroid-dependent nephrotic syndrome. However, there is no consensus on the optimal regimen and monitoring of rituximab. In other autoimmune diseases, anti-rituximab antibodies (ARA) have been reported in 10–40% of patients, but their clinical relevance remains unclear. In nephrotic syndrome, data are scarce.

Methods

We report a single-center retrospective study with immuno- and pharmacological monitoring of rituximab treatment in children with frequent relapsing (FR) or steroid-dependent nephrotic syndrome (SDNS). We analyzed the monthly monitoring of 24 children, receiving a dose of rituximab (375 mg/m2) between December 2017 and April 2018 at the Pediatric Nephrology Department of Robert-Debré hospital, Paris.

Results

ARA were detected in 7/24 patients (29%), sometimes after the first infusion of rituximab. ARA were present at baseline in two patients previously treated with rituximab. Both displayed no B-cell depletion. ARA were also reported in 5/22 patients during follow-up, with antibodies always detected in the first month following B-cell recovery. An incomplete CD19+CD20− B-cell depletion at M1 (5–25/mm3) and low serum rituximab levels was predictive of developing ARA. The development of de novo ARA during follow-up was not associated with shorter B-cell depletion.

Conclusions

This study shows that ARA are frequent in children with FR/SDNS and that close immuno- and pharmacological monitoring may help personalizing rituximab treatment in patients needing repeated injections.

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Authors and Affiliations

  1. Pediatric Department of Nephrology and Transplantation, Assistance Publique-Hôpitaux de Paris, Hôpital Robert-Debré, Paris, France

    Quentin Bertrand, Theresa Kwon, Anne Couderc, Anne Maisin, Alexandra Cambier, Véronique Baudouin, Georges Deschênes, Julien Hogan & Claire Dossier

  2. Departement of Immunology, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris, France

    Sabine Mignot & Marine Peyneau

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  1. Quentin Bertrand
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  2. Sabine Mignot
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Correspondence to Quentin Bertrand.

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Bertrand, Q., Mignot, S., Kwon, T. et al. Anti-rituximab antibodies in pediatric steroid-dependent nephrotic syndrome. Pediatr Nephrol 37, 357–365 (2022). https://doi.org/10.1007/s00467-021-05069-w

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