{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:21:25Z","timestamp":1791908485238,"version":"4.3.4"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,7,20]],"date-time":"2009-07-20T00:00:00Z","timestamp":1248048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2010,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We investigated interferon\u2010stimulated gene 15 (ISG15), a poorly understood ubiquitin\u2010like modifier, and its enzymatic pathway in dermatomyositis (DM), an autoimmune disease primarily involving muscle and skin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We generated microarray data measuring transcript abundance for approximately 18,000 genes in each of 113 human muscle biopsy specimens, and studied biopsy specimens and cultured skeletal muscle using immunohistochemistry, immunoblotting proteomics, real\u2010time quantitative polymerase chain reaction, and laser\u2010capture microdissection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Transcripts encoding ISG15\u2010conjugation pathway proteins were markedly upregulated in DM with perifascicular atrophy (DM\u2010PFA) muscle (ISG15 339\u2010fold, HERC5 62\u2010fold, and USP18 68\u2010fold) compared with 99 non\u2010DM samples. Combined analysis with publicly available microarray datasets showed that &gt;50\u2010fold ISG15 transcript elevation had 100% sensitivity and specificity for 28 biopsies from adult DM\u2010PFA and juvenile DM patients compared with 199 muscle samples from other muscle diseases. Free ISG15 and ISG15\u2010conjugated proteins were only found on immunoblots from DM\u2010PFA muscle. Cultured human skeletal muscle exposed to type 1 interferons produced similar transcripts and ISG15 protein and conjugates. Laser\u2010capture microdissection followed by proteomic analysis showed deficiency of titin in DM perifascicular atrophic myofibers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>A large\u2010scale microarray study of muscle samples demonstrated that among a diverse group of muscle diseases DM was uniquely associated with upregulation of the ISG15 conjugation pathway. Exposure of human skeletal muscle cell culture to type 1 interferons produced a molecular picture highly similar to that seen in human DM muscle. Perifascicular atrophic myofibers in DM were deficient in a number of skeletal muscle proteins including titin. 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