{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T11:57:48Z","timestamp":1776772668355,"version":"3.51.2"},"reference-count":55,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["K24 AR063120"],"award-info":[{"award-number":["K24 AR063120"]}],"id":[{"id":"10.13039\/100000069","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":[[2023,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Patients with diffuse cutaneous systemic sclerosis (dcSSc) display a complex clinical phenotype. Transcriptional profiling of whole blood or tissue from patients are affected by changes in cellular composition that drive gene expression and an inability to detect minority cell populations. We undertook this study to focus on the 2 main subtypes of circulating monocytes, classical monocytes (CMs) and nonclassical monocytes (NCMs) as a biomarker of SSc disease severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>SSc patients were recruited from the Prospective Registry for Early Systemic Sclerosis. Clinical data were collected, as well as peripheral blood for isolation of CMs and NCMs. Age\u2010, sex\u2010, and race\u2010matched healthy volunteers were recruited as controls. Bulk macrophages were isolated from the skin in a separate cohort. All samples were assayed by RNA sequencing (RNA\u2010seq).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We used an unbiased approach to cluster patients into 3 groups (groups A\u2013C) based on the transcriptional signatures of CMs relative to controls. Each group maintained their characteristic transcriptional signature in NCMs. Genes up\u2010regulated in group C demonstrated the highest expression compared to the other groups in SSc skin macrophages, relative to controls. Patients from groups B and C exhibited worse lung function than group A, although there was no difference in SSc skin disease at baseline, relative to controls. We validated our approach by applying our group classifications to published bulk monocyte RNA\u2010seq data from SSc patients, and we found that patients without skin disease were most likely to be classified as group A.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We are the first to show that transcriptional signatures of CMs and NCMs can be used to unbiasedly stratify SSc patients and correlate with disease activity outcome measures.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42380","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T05:15:21Z","timestamp":1666674921000},"page":"595-608","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Three Distinct Transcriptional Profiles of Monocytes Associate with Disease Activity in Scleroderma Patients"],"prefix":"10.1002","volume":"75","author":[{"given":"Hadijat\u2010Kubura M.","family":"Makinde","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Feinberg School of Medicine, Northwestern University  Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia L. 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Scott","family":"Budinger","sequence":"additional","affiliation":[{"name":"Division of Division of Pulmonary and Critical Care, Department of Medicine Feinberg School of Medicine, Northwestern University  Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8059-9978","authenticated-orcid":false,"given":"Shervin","family":"Assassi","sequence":"additional","affiliation":[{"name":"Prospective Registry of Early Systemic Sclerosis (PRESS) consortium, and Division of Rheumatology University of Texas Health Science Center at Houston"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5472-3840","authenticated-orcid":false,"given":"Tracy M.","family":"Frech","sequence":"additional","affiliation":[{"name":"PRESS consortium, and Division of Rheumatology and Immunology, Department of Medicine Vanderbilt University  Nashville 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