{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:22:08Z","timestamp":1787498528269,"version":"build-2736575974"},"reference-count":45,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"47","funder":[{"name":"Key R&D Program of Zhejiang","award":["2024C03170"],"award-info":[{"award-number":["2024C03170"]}]},{"name":"Key R&D Program of Zhejiang","award":["2024C03089"],"award-info":[{"award-number":["2024C03089"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,11,21]]},"abstract":"<jats:p>Uricase (UOX) is effective for treating refractory gout but is limited by antidrug antibody (ADA) formation, which leads to loss of efficacy and infusion reactions. Here, we demonstrate that a single coadministration of erythrocyte-conjugated UOX (UOX-Ery) with an immunosuppressant such as cyclophosphamide (CTX) induces robust and durable antigen-specific immune tolerance. This one-time intervention effectively prevented ADA formation in mice and rats, even after repeated challenges with UOX-Ery or free UOX protein, an outcome not achieved by CTX or UOX plus CTX. This tolerogenic effect relied on splenic uptake of UOX-Ery by myeloid cells, particularly macrophages, and was associated with the expansion of a distinct subset of effector regulatory T cells. Functionally, this immune tolerance enhanced the pharmacokinetics of UOX, sustained long-term control of serum uric acid levels, and attenuated local inflammation within tophus-like lesions. Together, these findings demonstrate that UOX-Ery, combined in a single dose with clinically used immunosuppressants, can effectively treat gout by inducing antigen-specific immune tolerance.<\/jats:p>","DOI":"10.1126\/sciadv.aea5196","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T18:58:54Z","timestamp":1763578734000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":3,"title":["Single coadministration of erythrocyte-uricase conjugate and immunosuppressant induces durable immune tolerance for gout therapy"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8756-7530","authenticated-orcid":true,"given":"Xiaoqian","family":"Nie","sequence":"first","affiliation":[{"name":"Research Center for Industries of the Future and School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310030, China."},{"name":"Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang 310024, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1531-2728","authenticated-orcid":true,"given":"Yuehua","family":"Liu","sequence":"additional","affiliation":[{"name":"Research Center for Industries of the Future and School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310030, China."},{"name":"Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang 310024, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9795-9722","authenticated-orcid":true,"given":"Xingyun","family":"Yao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310030, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6712-4521","authenticated-orcid":true,"given":"Chaohao","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310030, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2799-7421","authenticated-orcid":true,"given":"Xiaofei","family":"Gao","sequence":"additional","affiliation":[{"name":"Research Center for Industries of the Future and School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310030, China."},{"name":"Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang 310024, China."},{"name":"Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310030, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2017.04.008"},{"key":"e_1_3_2_3_2","first-page":"2093","article-title":"Rasburicase for tophaceous gout not treatable with allopurinol: An exploratory study","volume":"34","author":"Richette P.","year":"2007","unstructured":"P. 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