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Drug desensitization (DD) for BA allows transient clinical tolerance to the drug in reactive patients. The paper aimed to analyse the modification of drug-specific immune responses along DD in two patients with previous ADA-mediated HR (anaphylaxis) to rituximab and tocilizumab. The in vivo and in vitro assays of humoral and cellular response to drugs were carried out in a longitudinal manner throughout the DD cycles. We observed a progressive decrease of the pre-procedure ADA titer with negativization during the DD cycles in both patients. The monitoring of the drug-specific effector cell response showed the decrease in the BA-induced proliferation, while T cell response to unrelated antigens resulted unmodified along the DD cycles. Lastly, the increase of circulating drug-specific Treg cells mainly producing IL-35 were shown during the DD treatment. This study provides evidence that DD treatment to two BA inhibits humoral and cellular anti-drug response by increasing regulatory T cells and cytokines in an antigen-restricted manner. These modifications could contribute to the safety of the procedure.<\/jats:p>","DOI":"10.1038\/s41598-021-91851-7","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T10:04:25Z","timestamp":1623751465000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Drug-specific Treg cells are induced during desensitization procedure for rituximab and tocilizumab in patients with anaphylaxis"],"prefix":"10.1038","volume":"11","author":[{"given":"Alessandra","family":"Vultaggio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Nencini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Bormioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Silvestri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Dies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Vivarelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Maggi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Matucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,15]]},"reference":[{"issue":"6","key":"91851_CR1","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1016\/j.jaci.2009.09.009","volume":"124","author":"PJ Brennan","year":"2009","unstructured":"Brennan, P. 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