{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:28:52Z","timestamp":1791300532219,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,4,17]],"date-time":"2013-04-17T00:00:00Z","timestamp":1366156800000},"content-version":"vor","delay-in-days":47,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>We previously identified a circulating autoantibody against a 43 kDa muscle autoantigen in sporadic inclusion body myositis (IBM) and demonstrated the feasibility of an IBM diagnostic blood test. Here, we sought to identify the molecular target of this IBM autoantibody, understand the relationship between IBM autoimmunity and muscle degeneration, and develop an IBM blood test with high diagnostic accuracy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>IBM blood samples were screened using mass spectrometry and a synthetic human peptidome. Plasma and serum samples (N=200 patients) underwent immunoblotting assays, and results were correlated to clinical features. Muscle biopsy samples (n=30) were examined by immunohistochemistry and immunoblotting. Exome or whole genome sequencing was performed on DNA from 19 patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both mass spectrometry and screening of a 413,611 human peptide library spanning the entire human proteome identified cytosolic 5\u2032\u2010nucleotidase 1A (cN1A; NT5C1A) as the likely 43 kDa IBM autoantigen, which was then confirmed in dot blot and Western blot assays using recombinant cN1A protein. Moderate reactivity of anti\u2010cN1A autoantibodies was 70% sensitive and 92% specific, and high reactivity was 34% sensitive and 98% specific for the diagnosis of IBM. One to 3 major cN1A immunodominant epitopes were identified. cN1A reactivity by immunohistochemistry accumulated in perinuclear regions and rimmed vacuoles in IBM muscle, localizing to areas of myonuclear degeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Autoantibodies against cN1A are common in and highly specific to IBM among muscle diseases, and may provide a link between IBM's dual processes of autoimmunity and myodegeneration. Blood diagnostic testing is feasible and should improve early and reliable diagnosis of IBM. Ann Neurol 2013;73:408\u2013418<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.23840","type":"journal-article","created":{"date-parts":[[2012,12,22]],"date-time":"2012-12-22T14:33:23Z","timestamp":1356186803000},"page":"408-418","source":"Crossref","is-referenced-by-count":255,"title":["Cytosolic 5\u2032\u2010nucleotidase 1A autoimmunity in sporadic inclusion body myositis"],"prefix":"10.1002","volume":"73","author":[{"given":"H.","family":"Benjamin Larman","sequence":"first","affiliation":[{"name":"Department of Genetics Harvard University Medical School Boston MA"},{"name":"Division of Genetics, Department of Medicine Brigham and Women's Hospital Boston MA"},{"name":"Howard Hughes Medical Institute, Chevy Chase  MD"},{"name":"Division of Health Sciences and Technology Harvard\u2013Massachusetts Institute of Technology Cambridge MA"},{"name":"Department of Materials Science and Engineering Massachusetts Institute of Technology Cambridge 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