{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T11:38:41Z","timestamp":1761824321239,"version":"3.40.5"},"reference-count":21,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T00:00:00Z","timestamp":1631145600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Grant of Japan Kawasaki Disease Research Center"},{"name":"Life Innovation Platform YOKOHAMA"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Objective<\/jats:title><jats:p>Kawasaki disease (KD) is a systemic vasculitis in childhood that can lead to coronary artery lesions (CALs). Although early diagnosis and treatment is important for preventing KD patients from development of CALs, diagnosis depends on the clinical features of KD. We studied the usefulness of leucine-rich alpha-2-glycoprotein 1 (LRG1) and angiotensinogen (AGT), previously reported as KD-related proteins, for KD diagnosis and estimation of intravenous immunoglobulin (IVIG) efficacy.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Methods<\/jats:title><jats:p>We undertook a prospective cohort study with patients having two or more KD symptoms in multiple centers in Japan, between July 2017 and February 2019.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Results<\/jats:title><jats:p>Two hundred forty-two patients were included. In multivariable analysis, one unit increase in LRG1 was associated with higher odds of KD diagnosis (Odds ratio [OR] 1.02 [95% confidence interval (CI) 1.001\u20131.03]). Double-positivity for AGT (\u2265 26 \u03bcg\/mL) and LRG1 (\u2265 123.5 \u03bcg\/mL) was an independent biomarker for KD diagnosis in both the total cohort and the subgroup of patients with two to four KD symptoms (OR 5.01 [95% CI 1.86\u201313.50] and 3.71 [95% CI 1.23\u201311.16], respectively). There was no association between LRG1\/AGT and IVIG efficacy.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Conclusion<\/jats:title><jats:p>Double-positivity for LRG1 and AGT is an biomarker for KD diagnosis, especially useful in diagnosing incomplete KD from non-KD. Future studies with larger cohorts should seek to determine whether LRG1 and AGT are valuable as definitive data referred at the diagnosis of KD and for estimating the risk of CALs.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0257138","type":"journal-article","created":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T18:02:24Z","timestamp":1631210544000},"page":"e0257138","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Leucine-rich alpha-2-glycoprotein 1 and angiotensinogen as diagnostic biomarkers for Kawasaki disease"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0153-7283","authenticated-orcid":true,"given":"Masakatsu","family":"Yanagimachi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayaka","family":"Fukuda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumiko","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mari","family":"Iwamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiho","family":"Takao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunihiro","family":"Oba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natsuko","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Kiyohara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dai","family":"Kuranobu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norimasa","family":"Tada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayako","family":"Nagashima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taku","family":"Ishii","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoko","family":"Ino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yayoi","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobutoshi","family":"Nawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeo","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5590-8126","authenticated-orcid":true,"given":"Takuya","family":"Naruto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiro","family":"Morio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shouzaburo","family":"Doi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2130-4866","authenticated-orcid":true,"given":"Masaaki","family":"Mori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,9,9]]},"reference":[{"issue":"1","key":"pone.0257138.ref001","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.rdc.2014.09.010","article-title":"Kawasaki 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Peptide hormone regulation of angiogenesis","volume":"89","author":"C Clapp","year":"2009","journal-title":"Physiol Rev"},{"issue":"3","key":"pone.0257138.ref014","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/bmt.2012.244","article-title":"Investigation of the freely available easy-to-use software \u2019EZR\u2019 for medical statistics","volume":"48","author":"Y Kanda","year":"2013","journal-title":"Bone Marrow Transplant"},{"key":"pone.0257138.ref015","first-page":"2849695","article-title":"An Angiotensinogen Gene Polymorphism (rs5050) Is Associated with the Risk of Coronary Artery Aneurysm in Southern Chinese Children with Kawasaki Disease","volume":"2019","author":"Y Liu","year":"2019","journal-title":"Dis Markers"},{"issue":"2","key":"pone.0257138.ref016","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1111\/cei.12832","article-title":"Kawasaki disease: a matter of innate immunity","volume":"186","author":"T Hara","year":"2016","journal-title":"Clin Exp Immunol"},{"issue":"4","key":"pone.0257138.ref017","doi-asserted-by":"crossref","first-page":"307","DOI":"10.2217\/bmm-2018-0324","article-title":"N-terminal probrain natriuretic peptide as biomarker for diagnosis of Kawasaki disease","volume":"13","author":"M Rodriguez-Gonzalez","year":"2019","journal-title":"Biomark Med"},{"issue":"8","key":"pone.0257138.ref018","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1093\/rheumatology\/keh593","article-title":"Diagnosing Kawasaki syndrome: the need for a new clinical tool","volume":"44","author":"G Simonini","year":"2005","journal-title":"Rheumatology (Oxford)"},{"issue":"4","key":"pone.0257138.ref019","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/s00431-011-1631-2","article-title":"Complete and incomplete Kawasaki disease: two sides of the same coin","volume":"171","author":"C Manlhiot","year":"2012","journal-title":"Eur J Pediatr"},{"issue":"1","key":"pone.0257138.ref020","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1093\/ecco-jcc\/jjw132","article-title":"Leucine-rich Alpha-2 Glycoprotein is a Serum Biomarker of Mucosal Healing in Ulcerative Colitis","volume":"11","author":"S Shinzaki","year":"2017","journal-title":"J Crohns Colitis"},{"key":"pone.0257138.ref021","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.cca.2015.07.004","article-title":"B-type Natriuretic Peptide circulating forms: Analytical and bioactivity issues","volume":"448","author":"TG Yandle","year":"2015","journal-title":"Clin Chim Acta"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0257138","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,8]],"date-time":"2023-01-08T22:38:36Z","timestamp":1673217516000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0257138"}},"subtitle":[],"editor":[{"given":"John Matthew","family":"Koomen","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,9,9]]},"references-count":21,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0257138","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2021,9,9]]}}}