{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T11:30:23Z","timestamp":1792150223994,"version":"4.4.0"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T00:00:00Z","timestamp":1619395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Juvenile idiopathic inflammatory\/immune myopathies (IIMs) constitute a highly heterogeneous group of disorders with diagnostic difficulties and prognostic uncertainties. Circulating myositis\u2010specific autoantibodies (MSAs) have been recognized as reliable tools for patient substratification. Considering the key role of type I interferon (IFN) up\u2010regulation in juvenile IIM, we undertook the present study to investigate whether IFN\u2010induced 15\u2010kd protein (ISG\u201015) could be a reliable biomarker for stratification and diagnosis and to better elucidate its role in juvenile IIM pathophysiology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study included 56 patients: 24 with juvenile dermatomyositis (DM), 12 with juvenile overlap myositis (OM), 10 with Duchenne muscular dystrophy, and 10 with congenital myopathies. Muscle biopsy samples were assessed by immunohistochemistry, immunoblotting, and real\u2010time quantitative polymerase chain reaction. Negative regulators of type I IFN (<jats:italic>ISG15<\/jats:italic> and <jats:italic>USP18<\/jats:italic>) and positive regulators of type I IFN (<jats:italic>DDX58<\/jats:italic> and <jats:italic>IFIH1<\/jats:italic>) were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>ISG15<\/jats:italic> expression discriminated patients with juvenile IIM from those with nonimmune myopathies and, among patients with juvenile IIM, discriminated those with DM from those with OM. Among patients with juvenile DM, up\u2010regulation of the type I IFN positive regulators <jats:italic>DDX58<\/jats:italic> and <jats:italic>IFIH1<\/jats:italic> was similar regardless of MSA status. In contrast, the highest levels of the type I IFN negative regulator <jats:italic>ISG15<\/jats:italic> were observed in patients who were positive for melanoma differentiation\u2013associated gene 5 (MDA\u20105). Finally, <jats:italic>ISG15<\/jats:italic> levels were inversely correlated with the severity of muscle histologic abnormalities and positively correlated with motor performance as evaluated by the Childhood Myositis Assessment Scale and by manual muscle strength testing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Muscle <jats:italic>ISG15<\/jats:italic> expression is strongly associated with juvenile DM, with patients exhibiting a different ISG\u201015 muscle signature according to their MSA class. Patients with juvenile DM who are positive for MDA\u20105 have higher expression of <jats:italic>ISG15<\/jats:italic> in both gene form and protein form compared to the other subgroups. Moreover, our data show that negative regulation of type I IFN correlates with milder muscle involvement.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41625","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T10:06:13Z","timestamp":1607940373000},"page":"1044-1052","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["From Diagnosis to Prognosis: Revisiting the Meaning of Muscle <i>ISG15<\/i> Overexpression in Juvenile Inflammatory Myopathies"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0258-4738","authenticated-orcid":false,"given":"Cyrielle","family":"Hou","sequence":"first","affiliation":[{"name":"Institut Mondor de Recherche Biom\u00e9dicale Universit\u00e9 Paris\u2010Est Cr\u00e9teil INSERM  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chlo\u00e9","family":"Durrleman","sequence":"additional","affiliation":[{"name":"Institut Mondor de Recherche Biom\u00e9dicale Universit\u00e9 Paris\u2010Est Cr\u00e9teil INSERM Centre de Reference pour les Maladies Neuromusculaires FILNEMUS  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baptiste","family":"Periou","sequence":"additional","affiliation":[{"name":"Institut Mondor de Recherche Biom\u00e9dicale Universit\u00e9 Paris\u2010Est Cr\u00e9teil INSERM H\u00f4pital Henri\u2010Mondor AP\u2010HP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Barnerias","sequence":"additional","affiliation":[{"name":"Centre de Reference pour les Maladies Neuromusculaires FILNEMUS  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Bodemer","sequence":"additional","affiliation":[{"name":"H\u00f4pital Necker\u2010Enfants Malades AP\u2010HP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Desguerre","sequence":"additional","affiliation":[{"name":"Centre de Reference pour les Maladies Neuromusculaires FILNEMUS  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Quartier","sequence":"additional","affiliation":[{"name":"H\u00f4pital Necker\u2010Enfants Malades AP\u2010HP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8057-333X","authenticated-orcid":false,"given":"Isabelle","family":"Melki","sequence":"additional","affiliation":[{"name":"Laboratoire de Neurog\u00e9n\u00e9tique et Neuroinflammation Institut Imagine H\u00f4pital Necker\u2010Enfants Malades AP\u2010HP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian I.","family":"Rice","sequence":"additional","affiliation":[{"name":"University of Manchester School of Biological Sciences  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu P.","family":"Rodero","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie et Biologie Mod\u00e9lisation et Immunologie pour la Th\u00e9rapie CNRS UMR 8601 Universit\u00e9 Paris\u2010Descartes  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1300-0187","authenticated-orcid":false,"given":"Jean\u2010Luc","family":"Charuel","sequence":"additional","affiliation":[{"name":"H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re AP\u2010HP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9deric","family":"Relaix","sequence":"additional","affiliation":[{"name":"Institut Mondor de Recherche Biom\u00e9dicale Universit\u00e9 Paris\u2010Est Cr\u00e9teil INSERM  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Bader\u2010Meunier","sequence":"additional","affiliation":[{"name":"H\u00f4pital Necker\u2010Enfants Malades AP\u2010HP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oisJ\u00e9r\u00f4me","family":"Authier","sequence":"additional","affiliation":[{"name":"Institut Mondor de Recherche Biom\u00e9dicale Universit\u00e9 Paris\u2010Est Cr\u00e9teil INSERM Centre de Reference pour les Maladies Neuromusculaires H\u00f4pital Henri\u2010Mondor AP\u2010HP FILNEMUS  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2190-6843","authenticated-orcid":false,"given":"Cyril","family":"Gitiaux","sequence":"additional","affiliation":[{"name":"Institut Mondor de Recherche Biom\u00e9dicale Universit\u00e9 Paris\u2010Est Cr\u00e9teil INSERM Centre de Reference pour les Maladies Neuromusculaires H\u00f4pital Necker\u2010Enfants Malades AP\u2010HP FILNEMUS  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40320"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000000222"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12444"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2019.10.005"},{"key":"e_1_2_6_6_1","first-page":"470","article-title":"Vasculopathy\u2010related clinical and pathological features are associated with severe juvenile dermatomyositis","volume":"55","author":"Gitiaux C","year":"2015","journal-title":"Rheumatology (Oxford)"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kex516"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000002575"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41236"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000653"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41096"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032713-120231"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.26.15623"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008128"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.1.211"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40328"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21805"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2018-000811"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.59.8.1170"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199910)42:10<2213::AID-ANR25>3.0.CO;2-8"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23012"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12498"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kez525"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.3378"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11496"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13801"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24555"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2015.11.010"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20464"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4346"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.08.009"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.41625","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/art.41625","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.41625","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T20:32:11Z","timestamp":1759955531000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.41625"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,26]]},"references-count":30,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1002\/art.41625"],"URL":"https:\/\/doi.org\/10.1002\/art.41625","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,26]]},"assertion":[{"value":"2020-05-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}