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Here, we aimed to characterize the immunological impact of IL-1 blockade in this unique study population.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Patients\u2019 and control sera and supernatants of cells (whole blood, neutrophils, coronary artery endothelial cells) stimulated with recombinant IL-1\u03b2 were analyzed for single or multiple marker (<jats:italic>n<\/jats:italic>\u2009=\u200922) expression by ELISA or multiplexed bead array assay. Data were analyzed using unsupervised hierarchical clustering, multiple correlation, and multi-comparison statistics and were compared to retrospective analyses of KD transcriptomics.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Inflammation in IVIG-resistant KD (<jats:italic>n<\/jats:italic>\u2009=\u200916) is hallmarked by over-expression of innate immune mediators (particularly IL-6\u2009&gt;\u2009CXCL10\u2009&gt;\u2009S100A12\u2009&gt;\u2009IL-1Ra). Those as well as levels of immune or endothelial cell activation markers (sICAM-1, sVCAM-1) declined most significantly in course of anakinra treatment. Prior as well as following IL-1R blockade, over-expression of leucine-rich-\u03b12-glycoprotein 1 (LRG1) associated best with remnant inflammatory activity and the necessity to escalate anakinra dosage and separated inflammatory KD patients from sJIA-MAS (<jats:italic>n<\/jats:italic>\u2009=\u200913) and MIS-C (<jats:italic>n<\/jats:italic>\u2009=\u20094). Protein as well as retrospective gene expression analyses indicated tight association of LRG1 with IL-1\u03b2 signaling and neutrophilia, while particularly neutrophil stimulation with recombinant IL-1\u03b2 resulted in concentration-dependent LRG1 release.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our study identifies LRG1 as known trigger of endothelial activation and cardiac re-modeling to associate with IL-1\u03b2 signaling in KD. Besides a potential patho-mechanistic implication of these findings, our data suggest blood leukocyte and neutrophil counts to best predict response to IL-1Ra treatment in IVIG-resistant KD.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10875-022-01301-w","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T13:07:00Z","timestamp":1655212020000},"page":"1330-1341","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["An Immunological Axis Involving Interleukin 1\u03b2 and Leucine-Rich-\u03b12-Glycoprotein Reflects Therapeutic Response of Children with Kawasaki Disease: Implications from the KAWAKINRA Trial"],"prefix":"10.1007","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0638-2949","authenticated-orcid":false,"given":"Christoph","family":"Kessel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Kon\u00e9-Paut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Tellier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Belot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Masjosthusmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Wittkowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Fuehner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Rossi-Semerano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perrine","family":"Dusser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Marie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Boukhedouni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hel\u00e8ne","family":"Agostini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Piedvache","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Foell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,14]]},"reference":[{"key":"1301_CR1","doi-asserted-by":"publisher","first-page":"163","DOI":"10.3389\/fphar.2017.00163","volume":"8","author":"P Dusser","year":"2017","unstructured":"Dusser P, Kone-Paut I. 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Collection of MIS-C, sJIA-MAS, and HC serum was approved by the local (University Hospital Muenster: 2015\u2013670-f-S) ethical committee and parents or caregivers signed written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"All study participants (>\u200918\u00a0years) or (if\u2009<\u200918\u00a0years) their parents or caregivers signed written informed consent.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"No individual data (i.e., images, videos, personally identifiable details) are included in this study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"CK has received consulting fees from Novartis and Swedish Orphan Biovitrum (SOBI) (less than $10,000 each) and receives research support from Novartis; IKP has received consulting fees from AbbVie, Pfizer, Roche, Chugai, Novartis, SOBI, and Novimmune (less than $10,000 each). AB has received research support paid to his institution from AbbVie, Novartis, Pfizer, Roche Chugai, and Merck Serono. HW has received honoraria (lecture fees) from Novartis and Takeda, and travel support from Octapharma and CSL-Behring; DF received speaker fees\/honoraria from Chugai-Roche, Novartis, and SOBI as well as research support from Novartis, Pfizer, and SOBI. No other disclosures relevant to this article were reported.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}