{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T09:52:24Z","timestamp":1762854744718,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"a bequest donated by a late IBM patient who chose to remain confidential"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Muscles"],"abstract":"<jats:p>Inclusion body myositis (IBM) is a late-onset, treatment-resistant inflammatory myopathy. Approximately half of IBM patients develop autoantibodies against cytosolic 5\u2032-nucleotidase 1A (cN1A), but their role in disease pathogenesis remains unclear. This pilot study examined the effects of anti-cN1A-positive IBM serum on human primary myotubes\u2019 transcriptome profile, using anti-cN1A-negative IBM and healthy sera as controls. Exposure to anti-cN1A-positive serum altered the expression of 1126 genes, with upregulation of adaptive immune response genes, notably CTSH and CTSZ, encoding cathepsins H and Z. These findings were validated using a publicly available independent dataset comprising transcriptomes from fresh muscle tissue samples. NT5C1A mRNA, which encodes cN1A, was not detected in cultured myotubes regardless of the presence of autoantibodies. The findings suggest distinct pathological mechanisms in anti-cN1A-positive IBM, independent of direct antibody-target interactions. The role of cathepsins in IBM pathogenesis warrants further investigation.<\/jats:p>","DOI":"10.3390\/muscles4040053","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T13:51:08Z","timestamp":1762782668000},"page":"53","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Altered Transcriptome Signature in Primary Human Myotubes Exposed to Inclusion Body Myositis Serum: A Pilot Case Comparison of Anti-cN1A Positive and Negative Sera"],"prefix":"10.3390","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9979-6074","authenticated-orcid":false,"given":"Nataliya","family":"Slater","sequence":"first","affiliation":[{"name":"Personalised Medicine Center, School of Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, WA 6150, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5008-9080","authenticated-orcid":false,"given":"Abha","family":"Chopra","sequence":"additional","affiliation":[{"name":"Personalised Medicine Center, School of Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, WA 6150, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4827-4778","authenticated-orcid":false,"given":"Ramesh","family":"Ram","sequence":"additional","affiliation":[{"name":"Personalised Medicine Center, School of Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, WA 6150, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abbie","family":"Adams","sequence":"additional","affiliation":[{"name":"Personalised Medicine Center, School of Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, WA 6150, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank L.","family":"Mastaglia","sequence":"additional","affiliation":[{"name":"Perron Institute for Neurological and Translational Science, Nedlands, WA 6009, Australia"},{"name":"Centre for Neuromuscular & Neurological Disorders, University of Western Australia, Crawley, WA 6009, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6591-1444","authenticated-orcid":false,"given":"Merrilee","family":"Needham","sequence":"additional","affiliation":[{"name":"Personalised Medicine Center, School of Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, WA 6150, Australia"},{"name":"Perron Institute for Neurological and Translational Science, Nedlands, WA 6009, Australia"},{"name":"School of Medicine, University of Notre Dame Australia, Fremantle, WA 6160, Australia"},{"name":"Department of Neurology, Fiona Stanley Hospital, Murdoch, WA 6150, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6081-8494","authenticated-orcid":false,"given":"Jerome D.","family":"Coudert","sequence":"additional","affiliation":[{"name":"Personalised Medicine Center, School of Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, WA 6150, Australia"},{"name":"Perron Institute for Neurological and Translational Science, Nedlands, WA 6009, Australia"},{"name":"School of Medicine, University of Notre Dame Australia, Fremantle, WA 6160, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.nmd.2024.03.001","article-title":"272nd ENMC international workshop: 10 Years of progress-revision of the ENMC 2013 diagnostic criteria for inclusion body myositis and clinical trial readiness. 16\u201318 June 2023, Hoofddorp, The Netherlands","volume":"37","author":"Lilleker","year":"2024","journal-title":"Neuromuscul. 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