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Biochemical analyses of plasma IL-1Ra were performed by native Western blots and isoelectric focusing. Functional activity of the autoantibodies was examined by an in vitro IL-1\u03b2-signaling reporter assay.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Anti-IL-1-Ra IgG were identified in 7 (27%) out of 29 Still\u2019s disease patients, including 4\/23 with AOSD and 3\/6 with sJIA and coincided with a hyperphosphorylated isoform of endogenous IL-1Ra. Anti-IL-36Ra antibodies were found in 2 AOSD patients. No anti-PGRN or anti-IL-18BP antibodies were detected. Selective testing for anti-IL-1Ra antibodies in an independent cohort (sJIA, n\u2009=\u200934) identified 5 of 34 (14.7%) as seropositive. Collectively, 8\/12 antibody-positive Still\u2019s disease patients were either new-onset active disease or unresponsive to IL-1 blocking drugs. Autoantibody-seropositivity associated with decreased IL-1Ra plasma\/serum levels. Seropositive plasma impaired in vitro IL-1Ra bioactivity, which could be reversed by anakinra or canakinumab treatment.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Autoantibodies neutralizing IL-1Ra may represent a novel patho-mechanism in a subgroup of Still\u2019s disease patients, which is sensitive to high-dose IL-1 blocking therapy.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10875-023-01642-0","type":"journal-article","created":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T09:02:26Z","timestamp":1705482146000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Autoantibody-Mediated Depletion of IL-1RA in Still\u2019s Disease and Potential Impact of IL-1 Targeting Therapies"],"prefix":"10.1007","volume":"44","author":[{"given":"Marie-Christin","family":"Hoffmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Cavalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Fadle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Cantoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evi","family":"Regitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Octavian","family":"Fleser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Klemm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Zaks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"St\u00f6ger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corrado","family":"Campochiaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Tomelleri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Baldissera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg Thomas","family":"Bittenbring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Zimmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Pfeifer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvan","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus-Dieter","family":"Preuss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Bewarder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Thurner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Fuehner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Foell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Dagna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Kessel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8167-2989","authenticated-orcid":false,"given":"Lorenz","family":"Thurner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,17]]},"reference":[{"issue":"13","key":"1642_CR1","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s12969-015-0047-3","volume":"20","author":"N Nirmala","year":"2015","unstructured":"Nirmala N, Brachat A, Feist E, Blank N, Specker C, Witt M, et al. 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All parents and patients provided written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"GC was recruited by Novartis after executing the study and writing the first draft and is presently an associate of Novartis. DF received speaker fees\/honoraria from Chugai-Roche, Novartis, and SOBI, as well as research support from Novartis, Pfizer, and SOBI. CK has received consulting fees from Novartis and Swedish Orphan Biovitrum (SOBI) (<\u2009US$10,000 each) and receives research support from Novartis (>\u2009US$10,000). LTh received travel grants from Abbvie and consultancy Astra-Zeneca and Incyte (less than US$10,000 each). The other authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"45"}}