{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T02:36:54Z","timestamp":1777689414018,"version":"3.51.4"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T00:00:00Z","timestamp":1580860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["KAKENHI 15K08790"],"award-info":[{"award-number":["KAKENHI 15K08790"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["17K16218"],"award-info":[{"award-number":["17K16218"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine the value of serological biomarkers of collagen degradation\/turnover as serum markers of organ involvement in patients with systemic sclerosis (SSc).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serum samples were obtained from 79 SSc patients and 19 healthy control subjects. Types I to VI collagen turnover, excluding type II collagen, were evaluated using nine serological biomarkers. Organ involvement, such as interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), esophageal motility disorder, lower gastrointestinal lesions, joint contractures and digital ulceration, were evaluated and correlated with serum biomarkers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among multiple serological biomarkers of collagen turnover, the mean level of C5M was higher in SSc (3.9\u00a0ng\/mL) than healthy subjects (2.6\u00a0ng\/mL). In addition, PRO\u2010C6 (12.6\u00a0ng\/mL vs 5.4\u00a0ng\/mL) and C6M (26.0\u00a0ng\/mL vs 16.7\u00a0ng\/mL) were higher in SSc than the controls. The modified Rodnan skin score correlated with PRO\u2010C3 and PRO\u2010C6. Serum level of C6M was higher in patients with ILD. Furthermore, serum levels of PRO\u2010C3, PRO\u2010C6, and C6M were higher in patients with PAH. The use of high levels of these biomarkers as risk factors of PAH showed that all patients with PAH had high levels of risk factors. Of note, two\u2010third of patients with serum PRO\u2010C3, PRO\u2010C6 and C6M values above the respective cut\u2010off values had PAH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study indicated that collagen turnover abnormality, especially type VI collagen, is not only important pathologically in skin sclerosis but also in organ involvement. These biomarkers of collagen turnover are potentially clinically useful as biomarkers of organ involvement in SSc.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1756-185x.13804","type":"journal-article","created":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T10:45:53Z","timestamp":1580899553000},"page":"532-539","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Correlation between serological biomarkers of extracellular matrix turnover and lung fibrosis and pulmonary artery hypertension in patients with systemic sclerosis"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9693-9263","authenticated-orcid":false,"given":"Satoshi","family":"Kubo","sequence":"first","affiliation":[{"name":"The First Department of Internal Medicine School of Medicine University of Occupational and Environmental Health Japan Kitakyushu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne Sofie","family":"Siebuhr","sequence":"additional","affiliation":[{"name":"Nordic Bioscience, Biomarkers and Research Herlev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne\u2010C.","family":"Bay\u2010Jensen","sequence":"additional","affiliation":[{"name":"Nordic Bioscience, Biomarkers and Research Herlev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pernille","family":"Juhl","sequence":"additional","affiliation":[{"name":"Nordic Bioscience, Biomarkers and Research Herlev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morten A.","family":"Karsdal","sequence":"additional","affiliation":[{"name":"Nordic Bioscience, Biomarkers and Research Herlev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yurie","family":"Satoh","sequence":"additional","affiliation":[{"name":"The First Department of Internal Medicine School of Medicine University of Occupational and Environmental Health Japan Kitakyushu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuyuki","family":"Todoroki","sequence":"additional","affiliation":[{"name":"The First Department of Internal Medicine School of Medicine University of Occupational and Environmental Health Japan Kitakyushu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhisa","family":"Nakano","sequence":"additional","affiliation":[{"name":"The First Department of Internal Medicine School of Medicine University of Occupational and Environmental Health Japan Kitakyushu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shingo","family":"Nakayamada","sequence":"additional","affiliation":[{"name":"The First Department of Internal Medicine School of Medicine University of Occupational and Environmental Health Japan Kitakyushu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiya","family":"Tanaka","sequence":"additional","affiliation":[{"name":"The First Department of Internal Medicine School of Medicine University of Occupational and Environmental Health Japan Kitakyushu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,2,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2011.149"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30933-9"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2013.46"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780390811"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI107827"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780331211"},{"key":"e_1_2_7_8_1","first-page":"S100","article-title":"The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI): a review of their usefulness and validity in rheumatoid arthritis","volume":"23","author":"Aletaha D","year":"2005","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_7_9_1","first-page":"288","article-title":"Systemic lupus erythematosus disease activity index 2000","volume":"29","author":"Gladman DD","year":"2002","journal-title":"J Rheumatol"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780230510"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38098"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204424"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780220205"},{"key":"e_1_2_7_14_1","first-page":"1281","article-title":"Inter and intraobserver variability of total skin thickness score (modified Rodnan TSS) in systemic sclerosis","volume":"22","author":"Clements P","year":"1995","journal-title":"J Rheumatol"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.079756"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kev441"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41232-016-0001-x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keh156"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.115568"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.33463"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2015.188"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.135.6.1351"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.169748"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1159\/000232587"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.13-3014"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00106008"},{"key":"e_1_2_7_27_1","article-title":"Increased remodelling of interstitial collagens and basement membrane is suppressed by treatment in patients with rheumatoid arthritis: serological evaluation of a one\u2010year prospective study of 149 Japanese patients","author":"Gudmann NS","year":"2018","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.14092"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-017-0509-x"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.114264"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30541"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00139009"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780370111"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2005.03.005"}],"container-title":["International Journal of Rheumatic Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2F1756-185X.13804","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1756-185X.13804","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1756-185X.13804","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1756-185X.13804","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T13:35:28Z","timestamp":1693834528000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1756-185X.13804"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,5]]},"references-count":33,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,4]]}},"alternative-id":["10.1111\/1756-185X.13804"],"URL":"https:\/\/doi.org\/10.1111\/1756-185x.13804","archive":["Portico"],"relation":{},"ISSN":["1756-1841","1756-185X"],"issn-type":[{"value":"1756-1841","type":"print"},{"value":"1756-185X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,5]]},"assertion":[{"value":"2018-11-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}