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We performed RNA\u2010sequencing analysis on skin biopsy samples and peripheral blood mononuclear cells (PBMCs) from SSc patients and unaffected controls to better understand the pathogenesis of SSc.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed these data 1) to test for case\/control differences and 2) to identify genes whose expression levels correlate with SSc severity as measured by local skin score, modified Rodnan skin thickness score (MRSS), forced vital capacity (FVC), or diffusing capacity for carbon monoxide (D\n                      <jats:sc>Lco<\/jats:sc>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that PBMCs from SSc patients showed a strong type I interferon signature. This signal was found to be replicated in the skin, with additional signals for increased extracellular matrix (ECM) genes, classical complement pathway activation, and the presence of B cells. Notably, we observed a marked decrease in the expression of\n                      <jats:italic>SPAG17<\/jats:italic>\n                      , a cilia component, in SSc skin. We identified genes that correlated with the MRSS, DL\n                      <jats:sc>co<\/jats:sc>\n                      , and FVC in SSc PBMCs and skin using weighted gene coexpression network analysis. These genes were largely distinct from the case\/control differentially expressed genes. In PBMCs, type I interferon signatures negatively correlated with the DL\n                      <jats:sc>co<\/jats:sc>\n                      . In SSc skin, ECM gene expression positively correlated with the MRSS. Network analysis of SSc skin genes that correlated with clinical features identified the noncoding RNAs\n                      <jats:italic>SOX9\u2010AS1<\/jats:italic>\n                      and\n                      <jats:italic>ROCR<\/jats:italic>\n                      , both near the\n                      <jats:italic>SOX9<\/jats:italic>\n                      locus, as highly connected, \u201chub\u2010like\u201d genes in the network.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These results identify noncoding RNAs and\n                      <jats:italic>SPAG17<\/jats:italic>\n                      as novel factors potentially implicated in the pathogenesis of SSc.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.42281","type":"journal-article","created":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T09:36:28Z","timestamp":1656408988000},"page":"108-119","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Alterations of the Primary Cilia Gene\n                    <i>SPAG17<\/i>\n                    and\n                    <i>SOX9<\/i>\n                    Locus Noncoding RNAs Identified by RNA\u2010Sequencing Analysis in Patients With Systemic Sclerosis"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5921-2399","authenticated-orcid":false,"given":"Elisha D. 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Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7178-9729","authenticated-orcid":false,"given":"Isaac A.","family":"Goldberg","sequence":"additional","affiliation":[{"name":"Scleroderma Program, Feinberg School of Medicine Northwestern University  Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Morales\u2010Heil","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Rheumatology Washington University  St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4873-2628","authenticated-orcid":false,"given":"Benjamin D.","family":"Korman","sequence":"additional","affiliation":[{"name":"Scleroderma Program, Feinberg School of Medicine Northwestern University  Chicago 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