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We studied a clinically homogeneous group of early diffuse cutaneous SSc patients not exposed to immunosuppressive drugs who were enrolled in a clinical trial and compared their immune parameters to healthy control subjects.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Lymphocyte subsets were enumerated by multi-parameter flow cytometry of peripheral blood mononuclear cells at baseline visit. Production of the cytokines IL-4 and IL-17 was measured by intracellular flow cytometry following T cell activation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>SSc patients had increased percentages of CD4+ T cells but lower percentages of CD8+ T cells versus controls. The CD28-negative population was expanded in SSc, in the CD4 subset. Striking expansion of CD319+ T cells was noted among the CD4+ cells, in which they were barely detectable in healthy subjects. Frequencies of IL-4 producing cells did not differ between SSc and controls, but expansion of IL-17 producing cells was observed in SSc. A higher proportion of CD319+ cells produced cytokines, compared to other CD4+ cells. Numbers of activated T cells, regulatory T cells, and B cells were similar in SSc and control groups. Circulating follicular helper but not peripheral helper T cells were slightly expanded in SSc.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>In this carefully selected group of early diffuse cutaneous SSc patients, analysis of immune cell parameters has identified abnormalities that likely reflect disease pathogenesis and that are candidate biomarkers for sub-classification and targeted treatment. The CD4+CD319+ (SLAM-F7+) cells are cytotoxic and oligoclonal, were recently shown to be a dominant T cell population in perivascular lymphocytic infiltrates in SSc skin, actively secrete cytokines, and are emerging as a target for novel treatments of SSc.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13075-020-02383-w","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T18:03:54Z","timestamp":1609956234000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Lymphocyte subset abnormalities in early diffuse cutaneous systemic sclerosis"],"prefix":"10.1186","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0230-6607","authenticated-orcid":false,"given":"David A.","family":"Fox","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven K.","family":"Lundy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Whitfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Berrocal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Rasmussen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ray","family":"Ohara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Stinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikel","family":"Gurrea-Rubio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Wiewiora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Spino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Bush","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Furst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiv","family":"Pillai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh","family":"Khanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,6]]},"reference":[{"issue":"10103","key":"2383_CR1","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1016\/S0140-6736(17)30933-9","volume":"390","author":"CP Denton","year":"2017","unstructured":"Denton CP, Khanna D. 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He has received consultant fees from Pfizer, CSL Behring, and Juno Therapeutics, also unrelated.SKL is currently employed full-time at SystImmune Inc. doing work unrelated to the subject of this study. There are no competing interests.CS has received consultant fees from EICOS Sciences, Inc.SP is on the SAB of Abpro Inc. but this is not related to the subject to this study.DF has received grant support from Actelion, Amgen, BMS Corbus, Galapagos GSK, NIH, Novartis, Pfizer, Sanofi, and Roche\/Genentech. He has received consultant fees from Actelion, Amgen, BMS, Corbus, Galapagos Novartis, and Pfizer.Dr. Khanna reports personal consultancy fees as part of clinical trials design from Acceleron, Actelion, Blade Therapeutics, Galapagos, GSK, Mitsubishi Tanabi, Sanofi-Aventis\/Genzyme, and UCB Pharma and grants and personal consultancy fees from Bayer, BMS, and Genentech\/Roche during the conduct of this study. He has stock options in Eicos Sciences Inc. He is funded by the NIH\/ NIAMS K24 AR063120.MLW has received consulting fees from Bristol Myers Squib. Dr. Whitfield is a scientific founder and has received unrelated grant support from Celdara Medical LLC. He has received unrelated consulting fees from Abbvie, Acceleron, Celdara Medical, Corbus Pharmaceuticals, and Boeringer-Ingelheim.PC, SR, RO, AS, EW, VJB\u2014no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"10"}}