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Life\u2010limiting, progressive fibrotic changes as a consequence of vasculopathy and autoimmunity are characteristic in varying extent for lc<jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c and dc<jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c. Previously, an increased <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201033 serum concentration in early phase <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c patients and an elevated tissue expression of its receptor, <jats:styled-content style=\"fixed-case\">ST<\/jats:styled-content>2L, on endothelial cells (<jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content>) were described. While suggested as a biomarker for fibrotic diseases, for example liver fibrosis, the role of soluble <jats:styled-content style=\"fixed-case\">ST<\/jats:styled-content>2 (<jats:styled-content style=\"fixed-case\">sST<\/jats:styled-content>2) in the pathological processes and its contribution to vascular fibrosis in <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c has not been investigated. Here, we showed that <jats:styled-content style=\"fixed-case\">sST<\/jats:styled-content>2 is elevated in late phase limited cutaneous <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c (lc<jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c) as compared to patients with shorter disease duration or with the diffuse subtype of <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c. We demonstrated that <jats:styled-content style=\"fixed-case\">sST<\/jats:styled-content>2, not <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201033, is significantly increased in serum of lc<jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c patients with disease duration over 9\u00a0years. Soluble <jats:styled-content style=\"fixed-case\">ST<\/jats:styled-content>2 was not elevated in healthy controls or in <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c patients with early skin involvement or disease duration shorter than 9\u00a0years. Furthermore, we observed that <jats:styled-content style=\"fixed-case\">sST<\/jats:styled-content>2 serum levels were lowered by iloprost (prostacyclin) treatment. After 5\u00a0days of iloprost infusion, <jats:styled-content style=\"fixed-case\">sST<\/jats:styled-content>2 serum levels fell in 6 of 7 patients. Therefore, we not only like to propose <jats:styled-content style=\"fixed-case\">sST<\/jats:styled-content>2 as a biomarker for progressive vascular fibrosis, but moreover, suggest that the involvement of <jats:styled-content style=\"fixed-case\">sST<\/jats:styled-content>2 in the pathogenesis of lc<jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c may be exploited therapeutically.<\/jats:p>","DOI":"10.1111\/sji.12317","type":"journal-article","created":{"date-parts":[[2015,6,20]],"date-time":"2015-06-20T01:09:15Z","timestamp":1434762555000},"page":"269-274","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Increased Serum Levels of the <scp>IL<\/scp>\u201033 Neutralizing <scp>sST<\/scp>2 in Limited Cutaneous Systemic Sclerosis"],"prefix":"10.1111","volume":"82","author":[{"given":"A.","family":"Wagner","sequence":"first","affiliation":[{"name":"pharmazentrum frankfurt\/ZAFES University Hospital Frankfurt Goethe University Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"K\u00f6hm","sequence":"additional","affiliation":[{"name":"Division of Rheumatology University Hospital Frankfurt Goethe University Frankfurt am Main Germany"},{"name":"Fraunhofer Institute for Molecular Biology and Applied Ecology IME Project Group Translational Medicine &amp; Pharmacology TMP Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Nordin","sequence":"additional","affiliation":[{"name":"Rheumatology Unit Department of Medicine Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Svenungsson","sequence":"additional","affiliation":[{"name":"Rheumatology Unit Department of Medicine Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.M.","family":"Pfeilschifter","sequence":"additional","affiliation":[{"name":"pharmazentrum frankfurt\/ZAFES University Hospital Frankfurt Goethe University Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4499-2510","authenticated-orcid":false,"given":"H. H.","family":"Radeke","sequence":"additional","affiliation":[{"name":"pharmazentrum frankfurt\/ZAFES University Hospital Frankfurt Goethe University Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,8,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2014.09.004"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003080"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2012.04.005"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201141629"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2014.03.004"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-011-1686-5"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-014-0037-0"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.119321"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1593\/tlo.12418"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204424"},{"key":"e_1_2_7_12_1","first-page":"1892","article-title":"Skin thickness score in systemic sclerosis: an assessment of interobserver variability in 3 independent studies","volume":"20","author":"Clements PJ","year":"1993","journal-title":"J Rheumatol"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.3109\/03009742.2014.926566"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2013-0093OC"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0079176"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38277"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.5306"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-201553"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.148247"},{"key":"e_1_2_7_20_1","first-page":"18","article-title":"Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis","volume":"37","author":"Cutolo M","year":"2000","journal-title":"J Rheumatol"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.33463"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-006-0425-9"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keq139"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903306"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-010-8198-y"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204487"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202814"},{"key":"e_1_2_7_28_1","first-page":"1573","article-title":"Criteria for the classification of early systemic sclerosis","volume":"28","author":"LeRoy EC","year":"2001","journal-title":"J Rheumatol"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2015.01.034"}],"container-title":["Scandinavian Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fsji.12317","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fsji.12317","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/sji.12317","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T23:03:37Z","timestamp":1696201417000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/sji.12317"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,18]]},"references-count":28,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,9]]}},"alternative-id":["10.1111\/sji.12317"],"URL":"https:\/\/doi.org\/10.1111\/sji.12317","archive":["Portico"],"relation":{},"ISSN":["0300-9475","1365-3083"],"issn-type":[{"value":"0300-9475","type":"print"},{"value":"1365-3083","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8,18]]},"assertion":[{"value":"2015-01-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-06-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-08-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}