{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:05:32Z","timestamp":1788584732971,"version":"build-2803163510"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T00:00:00Z","timestamp":1618185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Kawasaki disease (KD) is a febrile disease of childhood characterized by systemic vasculitis that can lead to coronary artery lesions (CAL). This was a prospective cohort study to determine the levels of the pentraxin 3 (PTX3), soluble CD24-Subtype (Presepsin) and N-terminal pro-brain natriuretic peptide (NT-pro BNP) in consecutive KD patients. From January 2013 to March 2015, all patients with KD admitted to Aichi Medical University Hospital who provided consent had their plasma saved before IVIG administration. In total, 97 cases were registered. 22 cases of incomplete KD were excluded from the outcome analysis. The total 75 cases were used for statistical analyses. A PTX3 threshold of &amp;gt;7.92 ng\/ml provided a specificity of 88.5 %, a sensitivity of 94.4 %, and a likelihood ratio as high as 15.92 for the diagnosis of KD compared with febrile non-KD controls. Although an echocardiographic diagnosis of CAL in the early course of the disease was confirmed in 24 cases, it was not in the remaining 51 cases. Neither NT-proBNP nor Presepsin had statistical significance for the prediction of the echocardiographic CAL diagnosis. Only PTX3 was significantly predictive of the echocardiographic CAL diagnosis (p=0.01). The PTX3 level was significantly higher in the intravenous immunoglobulin (IVIG) non-responders (45.9\u00b17.45) than in the IVIG responders (17.0 \u00b1 1.46 ng\/ml) (p&amp;lt; 0.001). The PTX3 level also correlated with the number of IVIG treatment courses needed to resolve fever (R\u00b2 =0.64). Persistent CAL (pCAL) formation was observed in three cases; one of aneurysm only and two aneurysms with dilatations. The patients with pCAL had significantly higher PTX3 levels (85 \u00b1 8.4 ng\/ml) than patients without pCAL (22 \u00b1 2.2 ng\/ml) (p&amp;lt; 0.0001). In terms of pCAL prediction, the area under the curve (AUC) of receiver operating characteristic ROC curve of PTX3 was 0.99, and it was significantly greater than that of Presepsin (0.67) or NT-proBNP (0.75). PTX3 is a soluble pattern recognition molecule that acts as a main component of the innate immune system. These data suggest that PTX3 can be utilized as a definitive biomarker for the prediction of IVIG resistance and subsequent CAL formation in patients with KD.<\/jats:p>","DOI":"10.3389\/fimmu.2021.624802","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T07:33:40Z","timestamp":1618212820000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["Increased Pentraxin 3 Levels Correlate With IVIG Responsiveness and Coronary Artery Aneurysm Formation in Kawasaki Disease"],"prefix":"10.3389","volume":"12","author":[{"given":"Toshiyuki","family":"Kitoh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Ohara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taichiro","family":"Muto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihisa","family":"Okumura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reizo","family":"Baba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Koizumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Yamagishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshige","family":"Mikamo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Daigo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Hamakubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,12]]},"reference":[{"key":"B1","first-page":"178","article-title":"Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children","volume":"16","author":"Kawasaki","year":"1967","journal-title":"Arerugi"},{"key":"B2","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1038\/nrmicro1853","article-title":"Searching for the cause of Kawasaki disease \u2014 cytoplasmic inclusion bodies provide new insight","volume":"6","author":"Rowley","year":"2008","journal-title":"Nat Rev Microbiol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.120.046657","article-title":"Medium- and Large-Vessel Vasculitis","volume":"143","author":"Saadoun","year":"2021","journal-title":"Circulation"},{"key":"B4","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1007\/s00431-017-2937-5","article-title":"Dissecting Kawasaki disease: a state-of-the-art review","volume":"176","author":"Dietz","year":"2017","journal-title":"Eur J Pediatr"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2014-307536","article-title":"The epidemiology of Kawasaki disease: a global update","volume":"100","author":"Singh","year":"2015","journal-title":"Arch Dis Child"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.94.6.1379","article-title":"Long-term consequences of Kawasaki disease. A 10- to 21-year follow-up study of 594 patients","volume":"94","author":"Kato","year":"1996","journal-title":"Circulation"},{"key":"B7","doi-asserted-by":"crossref","DOI":"10.1542\/peds.54.3.271","article-title":"Yanagawa H. A New Infantile Acute Febrile Mucocutaneous Lymph Node Syndrome (MLNS) Prevailing in Japan","volume":"54","author":"Kawasaki","year":"1974","journal-title":"Pediatrics"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(84)91504-6","article-title":"High-dose intravenous gammaglobulin for Kawasaki disease","volume":"2","author":"Furusho","year":"1984","journal-title":"Lancet"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199106063242305","article-title":"A Single Intravenous Infusion of Gamma Globulin as Compared with Four Infusions in the Treatment of Acute Kawasaki Syndrome","volume":"324","author":"Newburger","year":"1991","journal-title":"New Engl J Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.89.2.916","article-title":"Guidelines for long-term management of patients with Kawasaki disease. Report from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association","volume":"89","author":"Dajani","year":"1994","journal-title":"Circulation"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.105.592865","article-title":"Prediction of Intravenous Immunoglobulin Unresponsiveness in Patients With Kawasaki Disease","volume":"113","author":"Kobayashi","year":"2006","journal-title":"Circulation"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2006.03.050","article-title":"Prediction of resistance to intravenous immunoglobulin treatment in patients with Kawasaki disease","volume":"149","author":"Egami","year":"2006","journal-title":"J Pediatr"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-006-0223-z","article-title":"Prediction of non-responsiveness to standard high-dose gamma-globulin therapy in patients with acute Kawasaki disease before starting initial treatment","volume":"166","author":"Sano","year":"2007","journal-title":"Eur J Pediatr"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000145143.19711.78","article-title":"Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease","volume":"110","author":"Newburger","year":"2004","journal-title":"Circulation"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61930-2","article-title":"Efficacy of immunoglobulin plus prednisolone for prevention of coronary artery abnormalities in severe Kawasaki disease (RAISE study): a randomised, open-label, blinded-endpoints trial","volume":"379","author":"Kobayashi","year":"2012","journal-title":"Lancet"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000145143.19711.78","article-title":"Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Statement for Health Professionals From the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association","volume":"110","author":"Newburger","year":"2004","journal-title":"Circulation"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/1744-9987.13486","article-title":"Impact of infliximab administration before plasma exchange therapy on patients with Kawasaki disease","volume":"24","author":"Shimada","year":"2020","journal-title":"Ther Apher Dial"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00016.2017","article-title":"PTX3, a Humoral Pattern Recognition Molecule, in Innate Immunity, Tissue Repair, and Cancer","volume":"98","author":"Garlanda","year":"2018","journal-title":"Physiol Rev"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-200x.2005.02033.x","article-title":"Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition)","volume":"47","author":"Ayusawa","year":"2005","journal-title":"Pediatr Int"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-66-0096","article-title":"Guidelines for Diagnosis and Management of Cardiovascular Sequelae in Kawasaki Disease (JCS 2013)\u2013\u2005Digest Version\u2005\u2013","volume":"78","author":"Group","year":"2014","journal-title":"Circ J"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000252126.48375.d5","article-title":"Establishment of a high sensitivity plasma assay for human pentraxin3 as a marker for unstable angina pectoris","volume":"27","author":"Inoue","year":"2007","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e0143971","DOI":"10.1371\/journal.pone.0143971","article-title":"Clinical Performance of a New Soluble CD14-Subtype Immunochromatographic Test for Whole Blood Compared with Chemiluminescent Enzyme Immunoassay: Use of Quantitative Soluble CD14-Subtype Immunochromatographic Tests for the Diagnosis of Sepsis","volume":"10","author":"Sato","year":"2015","journal-title":"PloS One"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000002503","article-title":"Real-world Safety and Effectiveness of Infliximab in Pediatric Patients With Acute Kawasaki Disease: A Postmarketing Surveillance in Japan (SAKURA Study)","volume":"39","author":"Miura","year":"2020","journal-title":"Pediatr Infect Dis J"},{"key":"B24","doi-asserted-by":"publisher","first-page":"5130","DOI":"10.1038\/s41598-020-62043-6","article-title":"N-terminal pro-brain natriuretic peptide as a biomarker for predicting coronary artery lesion of Kawasaki disease","volume":"10","author":"Zheng","year":"2020","journal-title":"Sci Rep"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-011-9986-8","article-title":"Prediction of the risk of coronary arterial lesions in Kawasaki disease by brain natriuretic peptide","volume":"32","author":"Kaneko","year":"2011","journal-title":"Pediatr Cardiol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"R6","DOI":"10.1186\/cc13183","article-title":"Presepsin (soluble CD14 subtype) and procalcitonin levels for mortality prediction in sepsis: data from the Albumin Italian Outcome Sepsis trial","volume":"18","author":"Masson","year":"2014","journal-title":"Crit Care"},{"key":"B27","article-title":"Clinical Use of Presepsin Compared with That of Procalcitonin in Children with Sepsis","volume":"64","author":"Nakanishi","year":"2016","journal-title":"Rinsho Byori Jpn"},{"key":"B28","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.jcrc.2018.06.004","article-title":"Clinical study of Presepsin and Pentraxin3 in critically ill children","volume":"47","author":"El Gendy","year":"2018","journal-title":"J Crit Care"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12832","article-title":"Kawasaki disease: a matter of innate immunity","volume":"186","author":"Hara","year":"2016","journal-title":"Clin Exp Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1515\/cclm.2009.110","article-title":"Determination of physiological plasma pentraxin 3 (PTX3) levels in healthy populations","volume":"47","author":"Yamasaki","year":"2009","journal-title":"Clin Chem Lab Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200112)44:12<2841::AID-ART472>3.0.CO;2-6","article-title":"PTX3 in small-vessel vasculitides: an independent indicator of disease activity produced at sites of inflammation","volume":"44","author":"Fazzini","year":"2001","journal-title":"Arthritis Rheum"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2019.00823","article-title":"Pentraxin 3 in Cardiovascular Disease","volume":"10","author":"Ristagno","year":"2019","journal-title":"Front Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-200107000-00017","article-title":"Circulating levels of the long pentraxin PTX3 correlate with severity of infection in critically ill patients","volume":"29","author":"Muller","year":"2001","journal-title":"Crit Care Med"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073119","article-title":"Pentraxin-3 serum levels are associated with disease severity and mortality in patients with systemic inflammatory response syndrome","volume":"8","author":"Bastrup-Birk","year":"2013","journal-title":"PloS One"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01135","article-title":"PTX3 Intercepts Vascular Inflammation in Systemic Immune-Mediated Diseases","volume":"10","author":"Ramirez","year":"2019","journal-title":"Front Immunol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"E2038","DOI":"10.1016\/S0735-1097(11)62038-X","article-title":"PTX3, A New Biomarker for Vasculits, Predicts Intraveous Immunoglobulin Unrespnsiveness in Patients with Kawasaki Disease","volume":"57","author":"Katsube","year":"2011","journal-title":"J Am Coll Cardiol"},{"key":"B37","first-page":"76","article-title":"Predicting the treatment-resistant Kawasaki disease by biomarker, Tenascin C and Pentraxin 3","volume-title":"The 40th Annual Meeting of the Japanese Society of Kawasaki Disease","author":"Yoshikane","year":"2020"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2020.00295","article-title":"Elevated Levels of Pentraxin 3 Correlate With Neutrophilia and Coronary Artery Dilation During Acute Kawasaki Disease","volume":"8","author":"Ching","year":"2020","journal-title":"Front Pediatr"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.624802\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T03:24:54Z","timestamp":1724815494000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.624802\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,12]]},"references-count":38,"alternative-id":["10.3389\/fimmu.2021.624802"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.624802","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,12]]},"article-number":"624802"}}