{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T13:38:16Z","timestamp":1781357896610,"version":"3.54.1"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2017,9,15]],"date-time":"2017-09-15T00:00:00Z","timestamp":1505433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["26461571"],"award-info":[{"award-number":["26461571"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,2,7]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>To investigate the clinical significance of soluble tumour necrosis factor receptor (sTNF-R) II\/I ratio as an indicator of the diagnosis of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (s-JIA), we measured the serum sTNF-RI and II levels in 117 patients with s-JIA, including 29 patients with MAS, 15 with Epstein\u2013Barr virus-induced haemophagocytic lymphohistiocytosis (EBV-HLH), 15 with Kawasaki disease (KD) and 28 healthy controls (HCs). We determined their correlation with measurements of disease activity and severity. Furthermore, we measured serum interleukin (IL)-18 levels in patients with EBV-HLH and compared these in levels in patients with MAS. The sTNF-RII\/I ratio was elevated significantly in MAS and EBV-HLH patients compared with those in the acute phase of s-JIA and KD patients, whereas there were no significant differences between HCs and those in the acute phase of s-JIA. The sTNF-RII\/I ratio increased profoundly as MAS developed and correlated positively with disease activity. Serum IL-18 levels were elevated significantly in MAS patients compared with EBV-HLH patients. The monitoring of serum IL-18 and sTNF-RII\/I might be useful for the diagnosis of MAS and the differentiation between MAS and EBV-HLH.<\/jats:p>","DOI":"10.1111\/cei.13026","type":"journal-article","created":{"date-parts":[[2017,8,17]],"date-time":"2017-08-17T07:35:01Z","timestamp":1502955301000},"page":"349-355","source":"Crossref","is-referenced-by-count":43,"title":["Characteristic elevation of soluble TNF receptor II : I ratio in macrophage activation syndrome with systemic juvenile idiopathic arthritis"],"prefix":"10.1093","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1077-7772","authenticated-orcid":false,"given":"M","family":"Shimizu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Mizuta","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Nakagishi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, Hyogo Prefectural Kobe Children's Hospital, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Yachie","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,9,15]]},"reference":[{"key":"2021120808201652800_cei13026-bib-0001","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/gene.2012.3","article-title":"Macrophage activation syndrome as part of systemic juvenile idiopathic arthritis: diagnosis, genetics, pathophysiology and treatment","volume":"13","author":"Ravelli","year":"2012","journal-title":"Genes Immun"},{"key":"2021120808201652800_cei13026-bib-0002","first-page":"2513","article-title":"Macrophage activation syndrome \u2013 what's in a name!","volume":"30","author":"Ramanan","year":"2003","journal-title":"J Rheumatol"},{"key":"2021120808201652800_cei13026-bib-0003","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/nrrheum.2011.68","article-title":"Pathogenesis of systemic juvenile idiopathic arthritis: some answers, more questions","volume":"7","author":"Mellins","year":"2011","journal-title":"Nat Rev Rheumatol"},{"key":"2021120808201652800_cei13026-bib-0004","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1097\/00002281-200209000-00012","article-title":"Macrophage activation syndrome","volume":"14","author":"Ravelli","year":"2002","journal-title":"Curr Opin Rheumatol"},{"key":"2021120808201652800_cei13026-bib-0005","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1093\/rheumatology\/keq133","article-title":"Distinct cytokine profiles of systemic-onset juvenile idiopathic arthritis-associated macrophage activation syndrome with particular emphasis on the role of interleukin-18 in its pathogenesis","volume":"49","author":"Shimizu","year":"2010","journal-title":"Rheumatology (Oxford)"},{"key":"2021120808201652800_cei13026-bib-0006","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.clim.2015.06.005","article-title":"Interleukin-18 for predicting the development of macrophage activation syndrome in systemic juvenile idiopathic arthritis","volume":"160","author":"Shimizu","year":"2015","journal-title":"Clin Immunol"},{"key":"2021120808201652800_cei13026-bib-0007","first-page":"69","article-title":"Evaluation of measurement of human TNF in plasma by ELISA","volume":"10","author":"Engelberts","year":"1991","journal-title":"Lymphokine Cytokine Res"},{"key":"2021120808201652800_cei13026-bib-0008","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1093\/infdis\/169.2.420","article-title":"Serum levels of tumor necrosis factor-\u03b1 (TNF-\u03b1) and soluble TNF receptors in human immunodeficiency virus type I infection. 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