{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T03:32:53Z","timestamp":1782012773491,"version":"3.54.5"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T00:00:00Z","timestamp":1766188800000},"content-version":"vor","delay-in-days":1560,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2021,9,12]],"date-time":"2021-09-12T00:00:00Z","timestamp":1631404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013642","name":"Japan Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013642","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["15K19402"],"award-info":[{"award-number":["15K19402"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013642","name":"Japan Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013642","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["15K19402"],"award-info":[{"award-number":["15K19402"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Although soluble interleukin 2 receptor (sIL-2R) is a potentially useful biomarker in the diagnosis and evaluation of disease severity in patients with sarcoidosis, its prognostic implication in patients with cardiac sarcoidosis (CS) is unclear. We sought to investigate whether sIL-2R was associated with clinical outcomes and to clarify the relationship between sIL-2R levels and disease activity in patients with CS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We examined 83 consecutive patients with CS in our hospital who had available serum sIL-2R data between May 2003 and February 2020. The primary outcome was a composite of advanced atrioventricular block, ventricular tachycardia or ventricular fibrillation, heart failure hospitalization, and all-cause death. Inflammatory activity in the myocardium and lymph nodes was assessed by 18F-fluorideoxyglucose positron emission tomography\/computed tomography. During a median follow-up period of 2.96 (IQR 2.24\u20134.27) years, the primary outcome occurred in 24 patients (29%). Higher serum sIL-2R levels (&amp;gt;538 U\/mL, the median) were significantly related to increased incidence of primary outcome (P = 0.037). Multivariable Cox regression analysis showed that a higher sIL-2R was independently associated with an increased subsequent risk of adverse events (HR 3.71, 95% CI 1.63\u20138.44, P = 0.002), even after adjustment for significant covariates. sIL-2R levels were significantly correlated to inflammatory activity in lymph nodes (r = 0.346, P = 0.003) but not the myocardium (r = 0.131, P = 0.27).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Increased sIL-2R is associated with worse long-term clinical outcomes accompanied by increased systemic inflammatory activity in CS patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.13614","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T01:35:45Z","timestamp":1631496945000},"page":"5282-5292","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Association of High Serum Soluble Interleukin 2 Receptor Levels with Risk of Adverse Events in Cardiac Sarcoidosis"],"prefix":"10.1093","volume":"8","author":[{"given":"Yuta","family":"Kobayashi","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University , Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuma","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University , Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1043-0608","authenticated-orcid":false,"given":"Toshiyuki","family":"Nagai","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University , Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Hirata","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging, Faculty of Medicine and Graduate School of Medicine, Hokkaido University , Sapporo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satonori","family":"Tsuneta","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging, Faculty of Medicine and Graduate School of Medicine, Hokkaido University , Sapporo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiya","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University , Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Komoriyama","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University , Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiwamu","family":"Kamiya","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University , Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Konishi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University , Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Omote","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University , Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Ohira","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University , Sapporo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohsuke","family":"Kudo","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging, Faculty of Medicine and Graduate School of Medicine, Hokkaido University , Sapporo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Konno","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University , Sapporo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihisa","family":"Anzai","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University , Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,9,12]]},"reference":[{"key":"2026012114185999200_ehf213614-bib-0001","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1056\/NEJMra071714","article-title":"Sarcoidosis","volume":"357","author":"Iannuzzi","year":"2007","journal-title":"N Engl J Med."},{"key":"2026012114185999200_ehf213614-bib-0002","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/S0140-6736(13)60680-7","article-title":"Sarcoidosis","volume":"383","author":"Valeyre","year":"2014","journal-title":"Lancet"},{"key":"2026012114185999200_ehf213614-bib-0003","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1161\/CIRCULATIONAHA.114.011522","article-title":"Cardiac sarcoidosis: epidemiology, characteristics, and outcome over 25 years in a nationwide study","volume":"131","author":"Kandolin","year":"2015","journal-title":"Circulation."},{"key":"2026012114185999200_ehf213614-bib-0004","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1378\/chest.14-0139","article-title":"Incidence and prognostic significance of myocardial late gadolinium enhancement in patients with sarcoidosis without cardiac manifestation","volume":"146","author":"Nagai","year":"2014","journal-title":"Chest."},{"key":"2026012114185999200_ehf213614-bib-0005","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.jcmg.2016.05.009","article-title":"Prognostic value of myocardial scarring on CMR in patients with cardiac sarcoidosis","volume":"10","author":"Coleman","year":"2017","journal-title":"JACC Cardiovasc Imaging."},{"key":"2026012114185999200_ehf213614-bib-0006","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.ccm.2015.08.005","article-title":"Identifying novel biomarkers in sarcoidosis using genome-based approaches","volume":"36","author":"Casanova","year":"2015","journal-title":"Clin Chest Med."},{"key":"2026012114185999200_ehf213614-bib-0007","doi-asserted-by":"crossref","DOI":"10.1088\/1752-7155\/7\/4\/046003","article-title":"Measurement of neopterin, TGF-beta1 and ACE in the exhaled breath condensate of patients with sarcoidosis","volume":"7","author":"Ahmadzai","year":"2013","journal-title":"J Breath Res."},{"key":"2026012114185999200_ehf213614-bib-0008","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.intimp.2015.01.015","article-title":"Conventional markers in determination of activity of sarcoidosis","volume":"25","author":"Gungor","year":"2015","journal-title":"Int Immunopharmacol."},{"key":"2026012114185999200_ehf213614-bib-0009","article-title":"Sarcoidosis: Causes, Diagnosis, Clinical Features, and Treatments","volume":"10","author":"Jain","year":"2020","journal-title":"J Clin Med."},{"key":"2026012114185999200_ehf213614-bib-0010","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1016\/j.rmed.2007.03.002","article-title":"Potential biomarkers for diagnosis of sarcoidosis using proteomics in serum","volume":"101","author":"Bons","year":"2007","journal-title":"Respir Med."},{"key":"2026012114185999200_ehf213614-bib-0011","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1378\/chest.124.1.186","article-title":"Serum soluble interleukin-2 receptor measurement in patients with sarcoidosis: a clinical evaluation","volume":"124","author":"Grutters","year":"2003","journal-title":"Chest."},{"key":"2026012114185999200_ehf213614-bib-0012","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1373\/49.9.1510","article-title":"Potential usefulness of inflammatory markers to monitor respiratory functional impairment in sarcoidosis","volume":"49","author":"Rothkrantz-Kos","year":"2003","journal-title":"Clin Chem."},{"key":"2026012114185999200_ehf213614-bib-0013","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1016\/j.rmed.2011.08.012","article-title":"Inflammatory activity assessment by F18 FDG-PET\/CT in persistent symptomatic sarcoidosis","volume":"105","author":"Mostard","year":"2011","journal-title":"Respir Med."},{"key":"2026012114185999200_ehf213614-bib-0014","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1253\/circj.CJ-19-0508","article-title":"JCS 2016 guideline on diagnosis and treatment of cardiac sarcoidosis-digest version","volume":"83","author":"Terasaki","year":"2019","journal-title":"Circ J."},{"key":"2026012114185999200_ehf213614-bib-0015","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCIMAGING.115.003738","article-title":"Prognosis of myocardial damage in sarcoidosis patients with preserved left ventricular ejection fraction: risk stratification using cardiovascular magnetic resonance","volume":"9","author":"Murtagh","year":"2016","journal-title":"Circ Cardiovasc Imaging."},{"key":"2026012114185999200_ehf213614-bib-0016","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1007\/s12350-015-0226-0","article-title":"The effects of 18-h fasting with low-carbohydrate diet preparation on suppressed physiological myocardial (18)F-fluorodeoxyglucose (FDG) uptake and possible minimal effects of unfractionated heparin use in patients with suspected cardiac involvement sarcoidosis","volume":"23","author":"Manabe","year":"2016","journal-title":"J Nucl Cardiol."},{"key":"2026012114185999200_ehf213614-bib-0017","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0105682","article-title":"A semi-automated technique determining the liver standardized uptake value reference for tumor delineation in FDG PET-CT","volume":"9","author":"Hirata","year":"2014","journal-title":"PLoS One."},{"key":"2026012114185999200_ehf213614-bib-0018","article-title":"Quantitative assessment of cardiac hypermetabolism and perfusion for diagnosis of cardiac sarcoidosis","author":"Miller","year":"2020","journal-title":"J Nucl Cardiol."},{"key":"2026012114185999200_ehf213614-bib-0019","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1007\/s12350-017-1122-6","article-title":"Volume-based glucose metabolic analysis of FDG PET\/CT: The optimum threshold and conditions to suppress physiological myocardial uptake","volume":"26","author":"Manabe","year":"2019","journal-title":"J Nucl Cardiol."},{"key":"2026012114185999200_ehf213614-bib-0020","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/S0140-6736(03)12888-7","article-title":"Sarcoidosis","volume":"361","author":"Baughman","year":"2003","journal-title":"The Lancet."},{"key":"2026012114185999200_ehf213614-bib-0021","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/j.1365-2990.1997.tb01195.x","article-title":"Interleukin-1 expression in inflammatory myopathies: evidence of marked immunoreactivity in sarcoid granulomas and muscle fibres showing ischaemic and regenerative changes","volume":"23","author":"Authier","year":"1997","journal-title":"Neuropathol Appl Neurobiol."},{"key":"2026012114185999200_ehf213614-bib-0022","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/eji.1830200102","article-title":"Accessory factors involved in murine T cell activation. Distinct roles of interleukin 6, interleukin 1 and tumor necrosis factor","volume":"20","author":"Vink","year":"1990","journal-title":"Eur J Immunol."},{"key":"2026012114185999200_ehf213614-bib-0023","doi-asserted-by":"crossref","first-page":"3680","DOI":"10.4049\/jimmunol.139.11.3680","article-title":"Internalization of interleukin 2 (IL-2) by high affinity IL-2 receptors is required for the growth of IL-2-dependent T cell lines","volume":"139","author":"Kumar","year":"1987","journal-title":"J Immunol."},{"key":"2026012114185999200_ehf213614-bib-0024","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0223897","article-title":"Sensitivity and specificity of serum soluble interleukin-2 receptor for diagnosing sarcoidosis in a population of patients suspected of sarcoidosis","volume":"14","author":"Eurelings","year":"2019","journal-title":"PLoS One."},{"key":"2026012114185999200_ehf213614-bib-0025","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1111\/1346-8138.13792","article-title":"Serum soluble interleukin-2 receptor level is more sensitive than angiotensin-converting enzyme or lysozyme for diagnosis of sarcoidosis and may be a marker of multiple organ involvement","volume":"44","author":"Thi Hong Nguyen","year":"2017","journal-title":"J Dermatol."},{"key":"2026012114185999200_ehf213614-bib-0026","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1164\/ajrccm.156.5.97-02050","article-title":"Sarcoidosis: TNF-alpha release from alveolar macrophages and serum level of sIL-2R are prognostic markers","volume":"156","author":"Ziegenhagen","year":"1997","journal-title":"Am J Respir Crit Care Med."},{"key":"2026012114185999200_ehf213614-bib-0027","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1183\/09031936.00055213","article-title":"Prediction of relapse after discontinuation of infliximab therapy in severe sarcoidosis","volume":"43","author":"Vorselaars","year":"2014","journal-title":"Eur Respir J."},{"key":"2026012114185999200_ehf213614-bib-0028","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.jacc.2013.09.022","article-title":"Cardiac positron emission tomography enhances prognostic assessments of patients with suspected cardiac sarcoidosis","volume":"63","author":"Blankstein","year":"2014","journal-title":"J Am Coll Cardiol."},{"key":"2026012114185999200_ehf213614-bib-0029","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1161\/CIRCIMAGING.112.000289","article-title":"Is there an association between clinical presentation and the location and extent of myocardial involvement of cardiac sarcoidosis as assessed by (1)(8)F- fluorodoexyglucose positron emission tomography?","volume":"6","author":"Mc Ardle","year":"2013","journal-title":"Circ Cardiovasc Imaging."},{"key":"2026012114185999200_ehf213614-bib-0030","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1161\/CIRCULATIONAHA.118.034687","article-title":"Ventricular arrhythmias in cardiac sarcoidosis","volume":"138","author":"Okada","year":"2018","journal-title":"Circulation."},{"key":"2026012114185999200_ehf213614-bib-0031","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.amjcard.2009.03.068","article-title":"Comparison of necropsy findings in patients with sarcoidosis dying suddenly from cardiac sarcoidosis versus dying suddenly from other causes","volume":"104","author":"Tavora","year":"2009","journal-title":"Am J Cardiol."},{"key":"2026012114185999200_ehf213614-bib-0032","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1007\/s12350-014-9901-9","article-title":"Quantitative interpretation of FDG PET\/CT with myocardial perfusion imaging increases diagnostic information in the evaluation of cardiac sarcoidosis","volume":"21","author":"Ahmadian","year":"2014","journal-title":"J Nucl Cardiol."},{"key":"2026012114185999200_ehf213614-bib-0033","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1016\/j.jcmg.2019.11.021","article-title":"Prognostic value of (18)F-FDG PET using texture analysis in cardiac sarcoidosis","volume":"13","author":"Manabe","year":"2020","journal-title":"JACC Cardiovasc Imaging."},{"key":"2026012114185999200_ehf213614-bib-0034","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.amjcard.2020.08.007","article-title":"Utility of cardiac magnetic resonance imaging versus cardiac positron emission tomography for risk stratification for ventricular arrhythmias in patients with cardiac sarcoidosis","volume":"134","author":"Gowani","year":"2020","journal-title":"Am J Cardiol."},{"key":"2026012114185999200_ehf213614-bib-0035","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1016\/j.hrthm.2014.03.043","article-title":"HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis","volume":"11","author":"Birnie","year":"2014","journal-title":"Heart Rhythm."}],"container-title":["ESC Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ehf2.13614","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ehf2.13614","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/8\/6\/5282\/65570108\/eschf_8_6_5282.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/8\/6\/5282\/65570108\/eschf_8_6_5282.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T19:22:33Z","timestamp":1769023353000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eschf\/article\/8\/6\/5282\/8343669"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,12]]},"references-count":35,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,9,12]]},"published-print":{"date-parts":[[2021,12,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ehf2.13614","relation":{},"ISSN":["2055-5822"],"issn-type":[{"value":"2055-5822","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,12]]},"published":{"date-parts":[[2021,9,12]]},"assertion":[{"value":"2021-06-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}