{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T10:01:14Z","timestamp":1780048874659,"version":"3.53.1"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T00:00:00Z","timestamp":1646179200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T00:00:00Z","timestamp":1646179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004810","name":"Samfundet Folkh\u00e4lsan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004810","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007797","name":"Helsingin Yliopisto","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007797","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003756","name":"Biomedicum Helsinki-s\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003756","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004212","name":"P\u00e4ivikki ja Sakari Sohlbergin S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004212","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010135","name":"Finska L\u00e4kares\u00e4llskapet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010135","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008723","name":"Suomen L\u00e4\u00e4ketieteen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008723","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007417","name":"Paulon S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007417","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004012","name":"Jane ja Aatos Erkon S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004012","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9liuksen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Helsinki including Helsinki University Central Hospital"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Inclusion body myositis (IBM) has an unclear molecular etiology exhibiting both characteristic inflammatory T-cell activity and rimmed-vacuolar degeneration of muscle fibers. Using in-depth gene expression and splicing studies, we aimed at understanding the different components of the molecular pathomechanisms in IBM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed RNA-seq on RNA extracted from skeletal muscle biopsies of clinically and histopathologically defined IBM (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200924), tibial muscular dystrophy (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096), and histopathologically normal group (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20099). In a comprehensive transcriptomics analysis, we analyzed the differential gene expression, differential splicing and exon usage, downstream pathway analysis, and the interplay between coding and non-coding RNAs (micro RNAs and long non-coding RNAs).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We observe dysregulation of genes involved in calcium homeostasis, particularly affecting the T-cell activity and regulation, causing disturbed Ca\n                      <jats:sup>2+<\/jats:sup>\n                      -induced apoptotic pathways of T cells in IBM muscles. Additionally, LCK\/p56, which is an essential gene in regulating the fate of T-cell apoptosis, shows increased expression and altered splicing usage in IBM muscles.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Our analysis provides a novel understanding of the molecular mechanisms in IBM by showing a detailed dysregulation of genes involved in calcium homeostasis and its effect on T-cell functioning in IBM muscles. Loss of T-cell regulation is hypothesized to be involved in the consistent observation of no response to immune therapies in IBM patients. Our results show that loss of apoptotic control of cytotoxic T cells could indeed be one component of their abnormal cytolytic activity in IBM muscles.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-022-11029-7","type":"journal-article","created":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T12:02:46Z","timestamp":1646222566000},"page":"4161-4173","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Comprehensive transcriptomic analysis shows disturbed calcium homeostasis and deregulation of T lymphocyte apoptosis in inclusion body myositis"],"prefix":"10.1007","volume":"269","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3549-558X","authenticated-orcid":false,"given":"Mridul","family":"Johari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Vihola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Palmio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manu","family":"Jokela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per Harald","family":"Jonson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaakko","family":"Sarparanta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanna","family":"Huovinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Savarese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hackman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjarne","family":"Udd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,2]]},"reference":[{"key":"11029_CR1","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1212\/WNL.0000000000004333","volume":"89","author":"C Ikenaga","year":"2017","unstructured":"Ikenaga C, Kubota A, Kadoya M et al (2017) Clinicopathologic features of myositis patients with CD8-MHC-1 complex pathology. Neurology 89:1060\u20131068. https:\/\/doi.org\/10.1212\/WNL.0000000000004333","journal-title":"Neurology"},{"key":"11029_CR2","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1212\/wnl.56.3.323","volume":"56","author":"MC Dalakas","year":"2001","unstructured":"Dalakas MC, Koffman B, Fujii M, Spector S, Sivakumar K, Cupler E (2001) A controlled study of intravenous immunoglobulin combined with prednisone in the treatment of IBM. Neurology 56:323\u2013327. https:\/\/doi.org\/10.1212\/wnl.56.3.323","journal-title":"Neurology"},{"key":"11029_CR3","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1007\/s00415-012-6439-0","volume":"259","author":"H Cai","year":"2012","unstructured":"Cai H, Yabe I, Sato K et al (2012) Clinical, pathological, and genetic mutation analysis of sporadic inclusion body myositis in Japanese people. J Neurol 259:1913\u20131922. https:\/\/doi.org\/10.1007\/s00415-012-6439-0","journal-title":"J Neurol"},{"key":"11029_CR4","first-page":"17","volume":"24","author":"V Askanas","year":"2005","unstructured":"Askanas V, Engel WK (2005) Sporadic inclusion-body myositis: a proposed key pathogenetic role of the abnormalities of the ubiquitin-proteasome system, and protein misfolding and aggregation. Acta Myol 24:17\u201324","journal-title":"Acta Myol"},{"key":"11029_CR5","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1097\/00002281-199811000-00005","volume":"10","author":"V Askanas","year":"1998","unstructured":"Askanas V, Engel WK (1998) Sporadic inclusion-body myositis and hereditary inclusion-body myopathies: current concepts of diagnosis and pathogenesis. Curr Opin Rheumatol 10:530\u2013542. https:\/\/doi.org\/10.1097\/00002281-199811000-00005","journal-title":"Curr Opin Rheumatol"},{"key":"11029_CR6","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s11926-010-0102-5","volume":"12","author":"SA Greenberg","year":"2010","unstructured":"Greenberg SA (2010) Theories of the pathogenesis of inclusion body myositis. Curr Rheumatol Rep 12:221\u2013228. https:\/\/doi.org\/10.1007\/s11926-010-0102-5","journal-title":"Curr Rheumatol Rep"},{"key":"11029_CR7","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1093\/jnen\/nlv023","volume":"75","author":"A Hiniker","year":"2016","unstructured":"Hiniker A, Daniels BH, Margeta M (2016) T-cell-mediated inflammatory myopathies in HIV-positive individuals: a histologic study of 19 cases. J Neuropathol Exp Neurol 75:239\u2013245. https:\/\/doi.org\/10.1093\/jnen\/nlv023","journal-title":"J Neuropathol Exp Neurol"},{"key":"11029_CR8","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1212\/wnl.51.2.598","volume":"51","author":"AA Amato","year":"1998","unstructured":"Amato AA, Shebert RT (1998) Inclusion body myositis in twins. Neurology 51:598\u2013600. https:\/\/doi.org\/10.1212\/wnl.51.2.598","journal-title":"Neurology"},{"key":"11029_CR9","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1111\/ene.13244","volume":"24","author":"M Johari","year":"2017","unstructured":"Johari M, Arumilli M, Palmio J et al (2017) Association study reveals novel risk loci for sporadic inclusion body myositis. Eur J Neurol 24:572\u2013577. https:\/\/doi.org\/10.1111\/ene.13244","journal-title":"Eur J Neurol"},{"key":"11029_CR10","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1136\/annrheumdis-2019-215046","volume":"78","author":"S Rothwell","year":"2019","unstructured":"Rothwell S, Chinoy H, Lamb JA et al (2019) Focused HLA analysis in Caucasians with myositis identifies significant associations with autoantibody subgroups. Ann Rheum Dis 78:996\u20131002. https:\/\/doi.org\/10.1136\/annrheumdis-2019-215046","journal-title":"Ann Rheum Dis"},{"key":"11029_CR11","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1212\/wnl.59.8.1170","volume":"59","author":"SA Greenberg","year":"2002","unstructured":"Greenberg SA, Sanoudou D, Haslett JN et al (2002) Molecular profiles of inflammatory myopathies. Neurology 59:1170\u20131182. https:\/\/doi.org\/10.1212\/wnl.59.8.1170","journal-title":"Neurology"},{"key":"11029_CR12","doi-asserted-by":"publisher","first-page":"17016","DOI":"10.1073\/pnas.0708115104","volume":"104","author":"I Eisenberg","year":"2007","unstructured":"Eisenberg I, Eran A, Nishino I et al (2007) Distinctive patterns of microRNA expression in primary muscular disorders. Proc Natl Acad Sci USA 104:17016\u201317021. https:\/\/doi.org\/10.1073\/pnas.0708115104","journal-title":"Proc Natl Acad Sci USA"},{"key":"11029_CR13","doi-asserted-by":"publisher","first-page":"8024","DOI":"10.1038\/s41598-017-08603-9","volume":"7","author":"PD Hamann","year":"2017","unstructured":"Hamann PD, Roux BT, Heward JA et al (2017) Transcriptional profiling identifies differential expression of long non-coding RNAs in Jo-1 associated and inclusion body myositis. Sci Rep 7:8024. https:\/\/doi.org\/10.1038\/s41598-017-08603-9","journal-title":"Sci Rep"},{"key":"11029_CR14","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s40478-017-0427-7","volume":"5","author":"DR Amici","year":"2017","unstructured":"Amici DR, Pinal-Fernandez I, Mazala DA et al (2017) Calcium dysregulation, functional calpainopathy, and endoplasmic reticulum stress in sporadic inclusion body myositis. Acta Neuropathol Commun 5:24. https:\/\/doi.org\/10.1186\/s40478-017-0427-7","journal-title":"Acta Neuropathol Commun"},{"key":"11029_CR15","doi-asserted-by":"publisher","first-page":"2590","DOI":"10.1093\/brain\/awz207","volume":"142","author":"SA Greenberg","year":"2019","unstructured":"Greenberg SA, Pinkus JL, Kong SW, Baecher-Allan C, Amato AA, Dorfman DM (2019) Highly differentiated cytotoxic T cells in inclusion body myositis. Brain 142:2590\u20132604. https:\/\/doi.org\/10.1093\/brain\/awz207","journal-title":"Brain"},{"key":"11029_CR16","doi-asserted-by":"publisher","first-page":"e1193","DOI":"10.1212\/WNL.0000000000008128","volume":"93","author":"I Pinal-Fernandez","year":"2019","unstructured":"Pinal-Fernandez I, Casal-Dominguez M, Derfoul A et al (2019) Identification of distinctive interferon gene signatures in different types of myositis. Neurology 93:e1193\u2013e1204. https:\/\/doi.org\/10.1212\/WNL.0000000000008128","journal-title":"Neurology"},{"key":"11029_CR17","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1136\/annrheumdis-2019-216599","volume":"79","author":"I Pinal-Fernandez","year":"2020","unstructured":"Pinal-Fernandez I, Casal-Dominguez M, Derfoul A et al (2020) Machine learning algorithms reveal unique gene expression profiles in muscle biopsies from patients with different types of myositis. Ann Rheum Dis 79:1234\u20131242. https:\/\/doi.org\/10.1136\/annrheumdis-2019-216599","journal-title":"Ann Rheum Dis"},{"key":"11029_CR18","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1016\/j.nmd.2013.08.007","volume":"23","author":"MR Rose","year":"2013","unstructured":"Rose MR, Group EIW (2013) 188th ENMC International Workshop: Inclusion Body Myositis, 2-4 December 2011, Naarden, The Netherlands. Neuromuscul Disord 23:1044\u20131055. https:\/\/doi.org\/10.1016\/j.nmd.2013.08.007","journal-title":"Neuromuscul Disord"},{"key":"11029_CR19","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1086\/342380","volume":"71","author":"P Hackman","year":"2002","unstructured":"Hackman P, Vihola A, Haravuori H et al (2002) Tibial muscular dystrophy is a titinopathy caused by mutations in TTN, the gene encoding the giant skeletal-muscle protein titin. Am J Hum Genet 71:492\u2013500. https:\/\/doi.org\/10.1086\/342380","journal-title":"Am J Hum Genet"},{"key":"11029_CR20","doi-asserted-by":"publisher","first-page":"2833","DOI":"10.1016\/j.ajpath.2015.06.018","volume":"185","author":"S Huovinen","year":"2015","unstructured":"Huovinen S, Penttila S, Somervuo P et al (2015) Differential isoform expression and selective muscle involvement in muscular dystrophies. Am J Pathol 185:2833\u20132842. https:\/\/doi.org\/10.1016\/j.ajpath.2015.06.018","journal-title":"Am J Pathol"},{"key":"11029_CR21","doi-asserted-by":"publisher","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","volume":"34","author":"S Chen","year":"2018","unstructured":"Chen S, Zhou Y, Chen Y, Gu J (2018) fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics 34:i884\u2013i890. https:\/\/doi.org\/10.1093\/bioinformatics\/bty560","journal-title":"Bioinformatics"},{"key":"11029_CR22","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin A, Davis CA, Schlesinger F et al (2013) STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29:15\u201321. https:\/\/doi.org\/10.1093\/bioinformatics\/bts635","journal-title":"Bioinformatics"},{"key":"11029_CR23","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","volume":"30","author":"Y Liao","year":"2014","unstructured":"Liao Y, Smyth GK, Shi W (2014) featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30:923\u2013930. https:\/\/doi.org\/10.1093\/bioinformatics\/btt656","journal-title":"Bioinformatics"},{"key":"11029_CR24","doi-asserted-by":"publisher","first-page":"D109","DOI":"10.1093\/nar\/gkh023","volume":"32","author":"S Griffiths-Jones","year":"2004","unstructured":"Griffiths-Jones S (2004) The microRNA Registry. Nucleic Acids Res 32:D109-111. https:\/\/doi.org\/10.1093\/nar\/gkh023","journal-title":"Nucleic Acids Res"},{"key":"11029_CR25","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love MI, Huber W, Anders S (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15:550. https:\/\/doi.org\/10.1186\/s13059-014-0550-8","journal-title":"Genome Biol"},{"key":"11029_CR26","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1093\/biostatistics\/kxw041","volume":"18","author":"M Stephens","year":"2016","unstructured":"Stephens M (2016) False discovery rates: a new deal. Biostatistics 18:275\u2013294. https:\/\/doi.org\/10.1093\/biostatistics\/kxw041","journal-title":"Biostatistics"},{"key":"11029_CR27","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1186\/s12859-015-0670-5","volume":"16","author":"SW Hartley","year":"2015","unstructured":"Hartley SW, Mullikin JC (2015) QoRTs: a comprehensive toolset for quality control and data processing of RNA-Seq experiments. BMC Bioinformatics 16:224. https:\/\/doi.org\/10.1186\/s12859-015-0670-5","journal-title":"BMC Bioinformatics"},{"key":"11029_CR28","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw501","volume":"44","author":"SW Hartley","year":"2016","unstructured":"Hartley SW, Mullikin JC (2016) Detection and visualization of differential splicing in RNA-Seq data with JunctionSeq. Nucleic Acids Res 44:e127. https:\/\/doi.org\/10.1093\/nar\/gkw501","journal-title":"Nucleic Acids Res"},{"key":"11029_CR29","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu G, Wang LG, Han Y, He QY (2012) clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16:284\u2013287. https:\/\/doi.org\/10.1089\/omi.2011.0118","journal-title":"OMICS"},{"key":"11029_CR30","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.1109\/TVCG.2014.2346248","volume":"20","author":"A Lex","year":"2014","unstructured":"Lex A, Gehlenborg N, Strobelt H, Vuillemot R, Pfister H (2014) UpSet: visualization of intersecting sets. IEEE Trans Vis Comput Graph 20:1983\u20131992. https:\/\/doi.org\/10.1109\/TVCG.2014.2346248","journal-title":"IEEE Trans Vis Comput Graph"},{"key":"11029_CR31","doi-asserted-by":"publisher","first-page":"i436","DOI":"10.1093\/bioinformatics\/btz363","volume":"35","author":"G Sturm","year":"2019","unstructured":"Sturm G, Finotello F, Petitprez F et al (2019) Comprehensive evaluation of transcriptome-based cell-type quantification methods for immuno-oncology. Bioinformatics 35:i436\u2013i445. https:\/\/doi.org\/10.1093\/bioinformatics\/btz363","journal-title":"Bioinformatics"},{"key":"11029_CR32","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/nmeth.3337","volume":"12","author":"AM Newman","year":"2015","unstructured":"Newman AM, Liu CL, Green MR et al (2015) Robust enumeration of cell subsets from tissue expression profiles. Nat Methods 12:453\u2013457. https:\/\/doi.org\/10.1038\/nmeth.3337","journal-title":"Nat Methods"},{"key":"11029_CR33","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1002\/ana.24847","volume":"81","author":"A-K G\u00fcttsches","year":"2017","unstructured":"G\u00fcttsches A-K, Brady S, Krause K et al (2017) Proteomics of rimmed vacuoles define new risk allele in inclusion body myositis. Ann Neurol 81:227\u2013239. https:\/\/doi.org\/10.1002\/ana.24847","journal-title":"Ann Neurol"},{"key":"11029_CR34","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/j.bbamem.2013.07.009","volume":"1838","author":"N Joseph","year":"2014","unstructured":"Joseph N, Reicher B, Barda-Saad M (2014) The calcium feedback loop and T cell activation: how cytoskeleton networks control intracellular calcium flux. Biochim Biophys Acta 1838:557\u2013568. https:\/\/doi.org\/10.1016\/j.bbamem.2013.07.009","journal-title":"Biochim Biophys Acta"},{"key":"11029_CR35","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1146\/annurev.immunol.19.1.497","volume":"19","author":"RS Lewis","year":"2001","unstructured":"Lewis RS (2001) Calcium signaling mechanisms in T lymphocytes. Annu Rev Immunol 19:497\u2013521. https:\/\/doi.org\/10.1146\/annurev.immunol.19.1.497","journal-title":"Annu Rev Immunol"},{"key":"11029_CR36","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/1074-7613(95)90113-2","volume":"3","author":"BJ Calnan","year":"1995","unstructured":"Calnan BJ, Szychowski S, Chan FK, Cado D, Winoto A (1995) A role for the orphan steroid receptor Nur77 in apoptosis accompanying antigen-induced negative selection. Immunity 3:273\u2013282. https:\/\/doi.org\/10.1016\/1074-7613(95)90113-2","journal-title":"Immunity"},{"key":"11029_CR37","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1084\/jem.20080101","volume":"205","author":"J Thompson","year":"2008","unstructured":"Thompson J, Winoto A (2008) During negative selection, Nur77 family proteins translocate to mitochondria where they associate with Bcl-2 and expose its proapoptotic BH3 domain. J Exp Med 205:1029\u20131036. https:\/\/doi.org\/10.1084\/jem.20080101","journal-title":"J Exp Med"},{"key":"11029_CR38","doi-asserted-by":"publisher","first-page":"E8017","DOI":"10.1073\/pnas.1721049115","volume":"115","author":"M Liebmann","year":"2018","unstructured":"Liebmann M, Hucke S, Koch K et al (2018) Nur77 serves as a molecular brake of the metabolic switch during T cell activation to restrict autoimmunity. Proc Natl Acad Sci 115:E8017\u2013E8026. https:\/\/doi.org\/10.1073\/pnas.1721049115","journal-title":"Proc Natl Acad Sci"},{"key":"11029_CR39","doi-asserted-by":"publisher","first-page":"4323","DOI":"10.1093\/emboj\/19.16.4323","volume":"19","author":"HD Youn","year":"2000","unstructured":"Youn HD, Chatila TA, Liu JO (2000) Integration of calcineurin and MEF2 signals by the coactivator p300 during T-cell apoptosis. EMBO J 19:4323\u20134331. https:\/\/doi.org\/10.1093\/emboj\/19.16.4323","journal-title":"EMBO J"},{"key":"11029_CR40","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/s1074-7613(00)00010-8","volume":"13","author":"HD Youn","year":"2000","unstructured":"Youn HD, Liu JO (2000) Cabin1 represses MEF2-dependent Nur77 expression and T cell apoptosis by controlling association of histone deacetylases and acetylases with MEF2. Immunity 13:85\u201394. https:\/\/doi.org\/10.1016\/s1074-7613(00)00010-8","journal-title":"Immunity"},{"key":"11029_CR41","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1038\/nri1085","volume":"3","author":"E Palmer","year":"2003","unstructured":"Palmer E (2003) Negative selection\u2013clearing out the bad apples from the T-cell repertoire. Nat Rev Immunol 3:383\u2013391. https:\/\/doi.org\/10.1038\/nri1085","journal-title":"Nat Rev Immunol"},{"key":"11029_CR42","doi-asserted-by":"publisher","first-page":"R120","DOI":"10.1186\/ar2009","volume":"8","author":"K Raza","year":"2006","unstructured":"Raza K, Scheel-Toellner D, Lee CY et al (2006) Synovial fluid leukocyte apoptosis is inhibited in patients with very early rheumatoid arthritis. Arthritis Res Ther 8:R120. https:\/\/doi.org\/10.1186\/ar2009","journal-title":"Arthritis Res Ther"},{"key":"11029_CR43","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/s41584-019-0186-x","volume":"15","author":"SA Greenberg","year":"2019","unstructured":"Greenberg SA (2019) Inclusion body myositis: clinical features and pathogenesis. Nat Rev Rheumatol 15:257\u2013272. https:\/\/doi.org\/10.1038\/s41584-019-0186-x","journal-title":"Nat Rev Rheumatol"},{"key":"11029_CR44","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s13395-018-0152-3","volume":"8","author":"K Nakka","year":"2018","unstructured":"Nakka K, Ghigna C, Gabellini D, Dilworth FJ (2018) Diversification of the muscle proteome through alternative splicing. Skeletal Muscle 8:8. https:\/\/doi.org\/10.1186\/s13395-018-0152-3","journal-title":"Skeletal Muscle"},{"key":"11029_CR45","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.4049\/jimmunol.172.3.1437","volume":"172","author":"X-Z Yu","year":"2004","unstructured":"Yu X-Z, Levin SD, Madrenas J, Anasetti C (2004) Lck is required for activation-induced T cell death after TCR ligation with partial agonists. J Immunol 172:1437\u20131443. https:\/\/doi.org\/10.4049\/jimmunol.172.3.1437","journal-title":"J Immunol"},{"key":"11029_CR46","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.immuni.2007.07.015","volume":"27","author":"L McNeill","year":"2007","unstructured":"McNeill L, Salmond RJ, Cooper JC et al (2007) The differential regulation of Lck kinase phosphorylation sites by CD45 is critical for T cell receptor signaling responses. Immunity 27:425\u2013437. https:\/\/doi.org\/10.1016\/j.immuni.2007.07.015","journal-title":"Immunity"},{"key":"11029_CR47","doi-asserted-by":"publisher","first-page":"370","DOI":"10.4161\/chan.21947","volume":"6","author":"JL Thompson","year":"2012","unstructured":"Thompson JL, Shuttleworth TJ (2012) A plasma membrane-targeted cytosolic domain of STIM1 selectively activates ARC channels, an arachidonate-regulated store-independent Orai channel. Channels (Austin) 6:370\u2013378. https:\/\/doi.org\/10.4161\/chan.21947","journal-title":"Channels (Austin)"},{"key":"11029_CR48","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1016\/j.neurobiolaging.2013.12.029","volume":"35","author":"A Cortese","year":"2014","unstructured":"Cortese A, Plagnol V, Brady S et al (2014) Widespread RNA metabolism impairment in sporadic inclusion body myositis TDP43-proteinopathy. Neurobiol Aging 35:1491\u20131498. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2013.12.029","journal-title":"Neurobiol Aging"},{"key":"11029_CR49","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.nmd.2014.12.009","volume":"25","author":"CC Weihl","year":"2015","unstructured":"Weihl CC, Baloh RH, Lee Y et al (2015) Targeted sequencing and identification of genetic variants in sporadic inclusion body myositis. Neuromuscul Disord 25:289\u2013296. https:\/\/doi.org\/10.1016\/j.nmd.2014.12.009","journal-title":"Neuromuscul Disord"},{"key":"11029_CR50","doi-asserted-by":"publisher","first-page":"218 e211","DOI":"10.1016\/j.neurobiolaging.2016.07.024","volume":"47","author":"Q Gang","year":"2016","unstructured":"Gang Q, Bettencourt C, Machado PM et al (2016) Rare variants in SQSTM1 and VCP genes and risk of sporadic inclusion body myositis. Neurobiol Aging 47:218 e211-218 e219. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2016.07.024","journal-title":"Neurobiol Aging"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-022-11029-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-022-11029-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-022-11029-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T12:28:50Z","timestamp":1658147330000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-022-11029-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,2]]},"references-count":50,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["11029"],"URL":"https:\/\/doi.org\/10.1007\/s00415-022-11029-7","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.06.30.450477","asserted-by":"object"}]},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,2]]},"assertion":[{"value":"15 October 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 February 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 February 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 March 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors report no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"The study was performed in line with the principles of the Declaration of Helsinki. Ethical approval for this study falls under HUS:195\/13\/03\/00\/11. Informed consent from the patients was obtained at the time of sample collection.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}