{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:24:00Z","timestamp":1788452640730,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100015391","name":"Myositis Association","doi-asserted-by":"publisher","award":["90097118"],"award-info":[{"award-number":["90097118"]}],"id":[{"id":"10.13039\/100015391","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01\u2010AR076390"],"award-info":[{"award-number":["R01\u2010AR076390"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS095969"],"award-info":[{"award-number":["R01 NS095969"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS082563"],"award-info":[{"award-number":["R01 NS082563"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["630399"],"award-info":[{"award-number":["630399"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Inclusion body myositis (IBM) is an idiopathic inflammatory myopathy with muscle pathology characterized by endomysial inflammation, rimmed vacuoles, and cytoplasmic mislocalization of transactive response DNA\u2010binding protein 43 (TDP\u201043). We aimed to determine whether loss of TDP\u201043 splicing repression led to the production of \u201ccryptic peptides\u201d that could be detected in muscle biopsies as a useful biomarker for IBM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used an antisera against a neoepitope encoded by a TDP\u201043\u2010dependent cryptic exon within hepatoma\u2010derived growth factor\u2010like protein 2 (\n                      <jats:italic>HDGFL2<\/jats:italic>\n                      ) for immunohistochemical analysis on muscle biopsy samples of 122 patients with IBM, 181 disease controls, and 16 healthy controls without abnormal muscle pathology. In situ hybridization was also utilized to detect the localization of cryptic\n                      <jats:italic>HDGFL2<\/jats:italic>\n                      transcripts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found cryptic\n                      <jats:italic>HDGFL2<\/jats:italic>\n                      peptides localized within myonuclei from muscle biopsies in 79 of 122 patients with IBM (65%), and this staining correlated with TDP\u201043 depletion. In contrast, cryptic\n                      <jats:italic>HDGFL2<\/jats:italic>\n                      immunoreactivity was absent in 197 muscle biopsies from a variety of disease controls, except for 2 patients with vacuolar myopathies. Notably, we show that cryptic\n                      <jats:italic>HDGFL2<\/jats:italic>\n                      transcripts are accompanied by the detection of cryptic\n                      <jats:italic>HDGFL2<\/jats:italic>\n                      in muscle fibers of IBM without rimmed vacuoles and TDP\u201043 aggregates.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Together, our findings establish that loss of TDP\u201043 splicing repression occurs in myonuclei of IBM skeletal muscle and suggest that detection of cryptic peptides in muscle biopsies may be a useful biomarker. We suggest that a therapeutic strategy designed to restore TDP\u201043 function should be considered to attenuate the degeneration of skeletal muscle in this devastating disease. ANN NEUROL 2025;97:629\u2013641<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.27167","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T04:20:12Z","timestamp":1736137212000},"page":"629-641","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Loss of\n                    <scp>TDP<\/scp>\n                    \u201043 Splicing Repression Occurs in Myonuclei of Inclusion Body Myositis Patients"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2264-1696","authenticated-orcid":false,"given":"Chiseko","family":"Ikenaga","sequence":"first","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew B.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine E.","family":"Irwin","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins University School of Medicine  Baltimore MD"},{"name":"Solomon H. 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