{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:22:39Z","timestamp":1790256159583,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Our goal was to study the tolerance and efficacy of two B cell depletion strategies, including one with CD19\u2010targeted chimeric antigen receptor (CAR) T cells, in a preclinical model mimicking the severe lung damages observed in systemic sclerosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>B cell depletion strategies were evaluated in the Fra\u20102 transgenic (Tg) mouse model. We considered a first group of 16 untreated mice, a second group of 15 mice receiving a single dose of anti\u2010CD20 monoclonal antibody (mAb), and a third group of 8 mice receiving CD19\u2010targeted CAR\u2010T cells in combination with anti\u2010CD20 monoclonal antibody. After six weeks of clinical evaluation, different validated markers of inflammation, lung fibrosis, and pulmonary vascular remodeling were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CD19\u2010targeted CAR\u2010T cells infusion in combination with anti\u2010CD20 mAb resulted in a deeper B cell depletion than anti\u2010CD20 mAb alone in the peripheral blood and lesional lungs of Fra\u20102 Tg mice. CAR\u2010T cell infusion worsened the clinical score and increased mortality in Fra\u20102 Tg mice. In line with the above findings, CAR\u2010T cell infusion significantly increased lung collagen content, the histological fibrosis score, and right ventricular systolic pressure. CAR\u2010T cells accumulated in lesional lungs and promoted T activation and inflammatory cytokine production. Treatment with anti\u2010CD20 mAb in monotherapy had no impact on lung inflammation\u2013driven fibrosis and pulmonary hypertension.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>B cell therapies failed to show efficacy in the Fra2 Tg mice. The exacerbated Fra\u20102 lung inflammatory burden stimulated accumulation and expansion of activated CD19\u2010targeted CAR\u2010T cells, secondarily inducing T cell activation and systemic inflammation, finally leading to disease worsening.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42677","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T09:17:42Z","timestamp":1692782262000},"page":"268-278","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Effects of B Cell Depletion by <scp>CD19\u2010Targeted<\/scp> Chimeric Antigen Receptor T Cells in a Murine Model of Systemic Sclerosis"],"prefix":"10.1002","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2463-218X","authenticated-orcid":false,"given":"J\u00e9r\u00f4me","family":"Avouac","sequence":"first","affiliation":[{"name":"INSERM U1016 and UMR8104, Institut Cochin and Universit\u00e9 Paris Cit\u00e9 and H\u00f4pital 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