@article{4a81e40f10464a78a22943079b495d07,
title = "Long-term exposure to monoclonal anti-TNF is associated with an increased risk of lymphoma in BAFF-transgenic mice",
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 to the soluble TNF receptor. We used B cell activating factor belonging to the TNF family (BAFF)-transgenic (Tg) mice as a model of autoimmunity-associated lymphoma. Six-month-old 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 euthanasia. Crude mortality and incidence of lymphoma were significantly higher in mice treated with monoclonal anti-TNF antibodies compared to both controls and mice treated with the soluble TNF receptor, even at a high dose. Flow cytometry analysis revealed decreased splenic macrophage infiltration in mice treated with monoclonal anti-TNF antibodies. Overall, this study demonstrates, for the first time, that a very prolonged treatment with monoclonal anti-TNF antibodies increase the risk of lymphoma in B cell-driven autoimmunity. These data suggest a closer monitoring for lymphoma development in patients suffering from B cell-driven autoimmune disease with long-term exposure to monoclonal anti-TNF antibodies.",
keywords = "anti-TNF, autoimmunity, BAFF, lymphoma, macrophages",
author = "Gaetane Nocturne and Bineta Ly and Audrey Paoletti and Juliette Pascaud and Raphaele Seror and Carole Nicco and Fabienne Mackay and Vincent, \{F. B.\} and Thierry Lazure and Sophie Ferlicot and Lev Stimmer and Quentin Pascal and Sandrine Roulland and Roman Krzysiek and Salima Hacein-Bey and Frederic Batteux and Xavier Mariette",
note = "Funding Information: Funding was obtained from the French Ministry of Research: ANR‐10‐LABX‐LERMIT, from Soci{\'e}t{\'e} Fran{\c c}aise de Rhumatologie and Fondation pour la Recherche M{\'e}dicale DEQ20150934719: Sj{\"o}gren{\textquoteright}s syndrome and Autoimmunity‐associated Lymphomas (SAIL). An unrestricted grant was also obtained from Pfizer. The authors thank Christiane Ch{\'e}reau, Marine, Stephane Bloquet and Axel Perrot for their help in mouse housing and Katia Posseme and Nathalie Ba for their support for tissue processing for histopathology. The authors also thank Christopher Mueller for his help and advice concerning macrophages experiments and Manon Zala for her help in the V(D)J rearrangement analysis. Funding Information: Funding was obtained from the French Ministry of Research: ANR-10-LABX-LERMIT, from Soci?t? Fran?aise de Rhumatologie and Fondation pour la Recherche M?dicale DEQ20150934719: Sj?gren?s syndrome and Autoimmunity-associated Lymphomas (SAIL). An unrestricted grant was also obtained from Pfizer. The authors thank Christiane Ch?reau, Marine, Stephane Bloquet and Axel Perrot for their help in mouse housing and Katia Posseme and Nathalie Ba for their support for tissue processing for histopathology. The authors also thank Christopher Mueller for his help and advice concerning macrophages experiments and Manon Zala for her help in the V(D)J rearrangement analysis. Publisher Copyright: {\textcopyright} 2021 British Society for Immunology. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = aug,
doi = "10.1111/cei.13602",
language = "English",
volume = "205",
pages = "169--181",
journal = "Clinical \& Experimental Immunology",
issn = "0009-9104",
publisher = "Wiley-Blackwell",
number = "2",
}