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Long-term exposure to monoclonal anti-TNF is associated with an increased risk of lymphoma in BAFF-transgenic mice
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  • Gaetane Nocturne,
  • Bineta Ly,
  • Audrey Paoletti,
  • Juliette Pascaud,
  • Raphaele Seror,
  • Carole Nicco,
  • Fabienne Mackay,
  • F.B. Vincent,
  • Thierry Lazure,
  • Sophie Ferlicot,
  • Lev Stimmer,
  • Sandrine Roulland,
  • Roman Krzysiek,
  • Salima Hacein Bey,
  • Frederic Batteux,
  • Xavier Mariette
Gaetane Nocturne
Universite Paris Sud Faculte de Medecine
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Bineta Ly
INSERM
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Audrey Paoletti
INSERM
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Juliette Pascaud
INSERM
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Raphaele Seror
INSERM
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Carole Nicco
Université Paris Descartes
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Fabienne Mackay
Monash University Central Clinical School
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F.B. Vincent
Monash University
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Thierry Lazure
APHP
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Sophie Ferlicot
APHP
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Lev Stimmer
INSERM-CEA
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Sandrine Roulland
Aix-Marseille Universite
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Roman Krzysiek
APHP
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Salima Hacein Bey
APHP
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Frederic Batteux
APHP
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Xavier Mariette
INSERM
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Abstract

The impact of treatment on the risk of lymphoma in patients with rheumatoid arthritis (RA) is unclear. Here, we aimed to assess if the risk of lymphoma differs according to the type of Tumor Necrosis factor inhibitor (TNFi), comparing monoclonal anti-TNF antibodies (Ab) to the soluble TNF receptor. We used BAFF-transgenic (Tg) mice as a model of autoimmunity-associated lymphoma. Six-month aged BAFF-Tg mice were treated with TNFi for 12 months. Histological examination of the spleen, assessment of the cellular composition of the spleen by flow cytometry and assessment of B cell clonality were performed at sacrifice. Crude mortality and incidence of lymphoma were significantly higher in mice treated with monoclonal anti-TNF Ab compared to both controls and mice treated with the soluble TNF receptor, even at high dose. Flow cytometry analysis revealed decreased splenic macrophage infiltration in mice treated with monoclonal anti-TNF Ab. Overall, this study demonstrates, for the first time, that a very prolonged treatment with monoclonal anti-TNF Ab increase the risk of lymphoma in B cell-driven autoimmunity. This data suggests a closer monitoring for lymphoma development in patients suffering from B cell-driven autoimmune disease with long-term exposure to monoclonal anti-TNF Ab.

Peer review status:ACCEPTED

15 Dec 2020Submitted to Clinical & Experimental Immunology
16 Dec 2020Submission Checks Completed
16 Dec 2020Assigned to Editor
17 Dec 2020Reviewer(s) Assigned
04 Jan 2021Review(s) Completed, Editorial Evaluation Pending
04 Jan 2021Editorial Decision: Revise Major
13 Mar 20211st Revision Received
15 Mar 2021Reviewer(s) Assigned
22 Mar 2021Review(s) Completed, Editorial Evaluation Pending
22 Mar 2021Editorial Decision: Accept