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The goal of this study was to identify skin biomarkers that could be prognostic for the progression of skin fibrosis in patients with early diffuse cutaneous <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c (dc<jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed clinical data and gene expression in skin biopsy samples from 38 placebo\u2010treated patients, part of the Roche Safety and Efficacy of Subcutaneous Tocilizumab in Adults with Systemic Sclerosis (<jats:styled-content style=\"fixed-case\">FASSCINATE<\/jats:styled-content>) phase <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> study of tocilizumab in <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c. <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> samples were analyzed using <jats:styled-content style=\"fixed-case\">nC<\/jats:styled-content>ounter. A\u00a0trajectory model based on a modified Rodnan skin thickness score was used to describe 3 skin disease trajectories over time. We examined the association of skin gene expression with skin score trajectory groups, by chi\u2010square test. Logistic regression was used to examine the prognostic power of each gene identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that placebo\u2010treated patients with high expression of messenger <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> for <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>14, <jats:styled-content style=\"fixed-case\">SERPINE<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>13<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">OSMR<\/jats:styled-content> at baseline were more likely to have progressive skin score trajectories. We also found that those genes were prognostic for the risk of\u00a0skin progression and that <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>13<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">OSMR<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">SERPINE<\/jats:styled-content>1 performed the best.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Skin gene expression of biomarkers associated with macrophages (<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>14, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>13<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>1) and transforming growth factor \u03b2 activation (<jats:styled-content style=\"fixed-case\">SERPINE<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> OSMR<\/jats:styled-content>) are prognostic for progressive skin disease in patients with dc<jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c. These biomarkers may provide guidance in decision\u2010making about which patients should be considered for aggressive therapies and\/or for clinical trials.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40455","type":"journal-article","created":{"date-parts":[[2018,5,31]],"date-time":"2018-05-31T17:32:38Z","timestamp":1527787958000},"page":"912-919","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Skin Gene Expression Is Prognostic for the Trajectory of Skin Disease in Patients With Diffuse Cutaneous Systemic Sclerosis"],"prefix":"10.1002","volume":"70","author":[{"given":"Giuseppina","family":"Stifano","sequence":"first","affiliation":[{"name":"Boston University School of Medicine Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Sornasse","sequence":"additional","affiliation":[{"name":"Genentech San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"Rice","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Na","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyin","family":"Chen\u2010Harris","sequence":"additional","affiliation":[{"name":"Genentech San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh","family":"Khanna","sequence":"additional","affiliation":[{"name":"University of Michigan Scleroderma Program Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelika","family":"Jahreis","sequence":"additional","affiliation":[{"name":"Genentech San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Siegel","sequence":"additional","affiliation":[{"name":"Genentech San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Lafyatis","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Medical Center Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,5,28]]},"reference":[{"key":"e_1_2_7_2_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_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.10589"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200011)43:11<2437::AID-ANR10>3.0.CO;2-U"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22721"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000113"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-205226"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-119-10-199311150-00007"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4598"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00232-4"},{"key":"e_1_2_7_11_1","unstructured":"Hoffmann\u2010La Roche sponsor.A phase II\/III multicenter randomized double\u2010blind placebo\u2010controlled study to assess the efficacy and safety of tocilizumab versus placebo in patients with systemic sclerosis. 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