{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T07:51:01Z","timestamp":1781769061774,"version":"3.54.5"},"reference-count":13,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"am","delay-in-days":323,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T00:00:00Z","timestamp":1714348800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005726","name":"Karen Brown Scleroderma Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005726","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01\u2010AR\u2010073284"],"award-info":[{"award-number":["R01\u2010AR\u2010073284"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R56\u2010AR\u2010078211"],"award-info":[{"award-number":["R56\u2010AR\u2010078211"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["N01\u2010AI\u201005419"],"award-info":[{"award-number":["N01\u2010AI\u201005419"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["HHSN 272201100025C"],"award-info":[{"award-number":["HHSN 272201100025C"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["W81XWH\u201022\u20101\u20100162"],"award-info":[{"award-number":["W81XWH\u201022\u20101\u20100162"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>In the randomized Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial, myeloablation, followed by hematopoietic stem cell transplantation (HSCT), led to the normalization of systemic sclerosis (SSc) peripheral blood cell (PBC) gene expression signature at the 26\u2010month visit. Herein, we examined long\u2010term molecular changes ensuing 54 months after randomization for individuals receiving an HSCT or 12 months of intravenous cyclophosphamide (CYC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Global PBC transcript studies were performed in study participants at pretreatment baseline and at 38 months and 54 months after randomization, as well as in healthy controls using Illumina HT\u201012 arrays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty (HSCT = 19 and CYC = 11) participants had 38\u2010month samples available, and 26 (HSCT = 16 and CYC = 11) had 54\u2010month samples available. In the paired comparison to baseline, a significant down\u2010regulation of interferon modules and an up\u2010regulation of cytotoxic\/natural killer module were observed at the 38\u2010month and 54\u2010month visits in the HSCT arm, indicating a long\u2010term normalization of baseline SSc gene expression signature. No differentially expressed modules were detected in the CYC arm. In comparison to samples from healthy controls, 38\u2010month visit samples in the HSCT arm showed an up\u2010regulation of B cell and plasmablast modules and a down\u2010regulation of myeloid and inflammation modules. Importantly, 54\u2010month HSCT samples did not show any differentially expressed modules compared to healthy control samples, suggesting completion of immune reconstitution. Participants in the CYC arm continued to show an SSc transcript signature in comparison to controls at both time points.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Paralleling the observed clinical benefit, HSCT leads to durable long\u2010term normalization of the molecular signature in SSc, with completion of immune resetting to 54 months after HSCT.<\/jats:p><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art42847-toc-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42847","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T04:25:28Z","timestamp":1710735928000},"page":"1288-1293","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Myeloablation Followed by Hematopoietic Stem Cell Transplantation and Long\u2010Term Normalization of Systemic Sclerosis Molecular Signatures"],"prefix":"10.1002","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5149-3966","authenticated-orcid":false,"given":"Nancy","family":"Wareing","sequence":"first","affiliation":[{"name":"UTHealth Houston McGovern Medical School  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Baylor Institute for Immunology Research  Dallas Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynette","family":"Keyes\u2010Elstein","sequence":"additional","affiliation":[{"name":"Rho Inc.  Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen A.","family":"Goldmuntz","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases, NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marka A.","family":"Lyons","sequence":"additional","affiliation":[{"name":"UTHealth Houston McGovern Medical School  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"McSweeney","sequence":"additional","affiliation":[{"name":"Colorado Blood Cancer Institute  Denver"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7857-2373","authenticated-orcid":false,"given":"Daniel E.","family":"Furst","sequence":"additional","affiliation":[{"name":"University of California Los Angeles, and University of Washington  Seattle"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Nash","sequence":"additional","affiliation":[{"name":"Colorado Blood Cancer Institute  Denver"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie J.","family":"Crofford","sequence":"additional","affiliation":[{"name":"Vanderbilt University  Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly","family":"Welch","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases, NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Pinckney","sequence":"additional","affiliation":[{"name":"Rho Inc.  Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5070-2535","authenticated-orcid":false,"given":"Maureen D.","family":"Mayes","sequence":"additional","affiliation":[{"name":"UTHealth Houston McGovern Medical School  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1379-9216","authenticated-orcid":false,"given":"Keith M.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Duke University  Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8059-9978","authenticated-orcid":false,"given":"Shervin","family":"Assassi","sequence":"additional","affiliation":[{"name":"UTHealth Houston McGovern Medical School  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60982-3"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.6368"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1703327"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-215770"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780230510"},{"issue":"2","key":"e_1_2_6_7_1","first-page":"202","article-title":"Scleroderma (systemic sclerosis): classification, subsets and pathogenesis","volume":"15","author":"LeRoy EC","year":"1988","journal-title":"J Rheumatol"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3642"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt660"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.24785"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keab257"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-019-1889-8"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2021-221925"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200702-326OC"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/am-pdf\/10.1002\/art.42847","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.42847","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T14:07:19Z","timestamp":1759932439000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.42847"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,29]]},"references-count":13,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1002\/art.42847"],"URL":"https:\/\/doi.org\/10.1002\/art.42847","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,29]]},"assertion":[{"value":"2023-06-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}