{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T04:29:11Z","timestamp":1785644951466,"version":"3.56.0"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction\/Aims<\/jats:title>\n                    <jats:p>Anti\u20103\u2010hydroxy\u20103\u2010methylglutaryl\u2010CoA reductase (HMGCR) autoantibodies (aAbs) are pathogenic in immune\u2010mediated necrotizing myopathy (IMNM), partly through complement activation. C5 inhibition did not restore muscle strength in mice or patients with overt IMNM, suggesting additional pathogenic mechanisms. In\u00a0vitro studies have suggested that anti\u2010HMGCR aAbs might impair myoblast fusion and myotube differentiation, but this has not been investigated in\u00a0vivo. This study aimed at assessing the impact of anti\u2010HMGCR aAbs on muscle regeneration in a mouse model of muscle necrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Muscle necrosis was induced by cardiotoxin (CTX) injection into the gastrocnemius of C57BL\/6 or C5\u2010deficient C57BL\/10 mice. Mice received intraperitoneal injections of IgG purified from an anti\u2010HMGCR\n                      <jats:sup>+<\/jats:sup>\n                      IMNM patient every other day. At Days 3 and 6, muscle strength was assessed, blood collected, and muscles frozen for histological analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In C5\u2010deficient mice, anti\u2010HMGCR\n                      <jats:sup>+<\/jats:sup>\n                      IgG did not impair muscle regeneration after CTX\u2010induced muscle damage. In contrast, in complement\u2010competent mice, aAbs reduced muscle strength (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0047), prolonged the presence of myofiber necrosis at Days 3 and 6 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0415 and\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0103), and decreased the number of Pax7\n                      <jats:sup>+<\/jats:sup>\n                      (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0317) and MyoG\n                      <jats:sup>+<\/jats:sup>\n                      (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0079) regenerating fibers by more than 50% at Day 6.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings establish the cytotoxicity of anti\u2010HMGCR aAbs on regenerating muscle cells through a primarily complement\u2010mediated mechanism, without directly impairing cellular regeneration per se. Given the still unmet medical needs of IMNM, C5 or upstream complement\u2010targeted therapies early in the disease course, as well as aAb reduction, B\/plasma cell depletion via CAR\u2010T cells or bispecific antibodies deserves further clinical investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mus.70016","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T08:50:22Z","timestamp":1756716622000},"page":"1300-1308","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Effect of Anti\u20103\u2010Hydroxy\u20103\u2010Methylglutaryl\u2010\n                    <scp>CoA<\/scp>\n                    Reductase (\n                    <scp>HMGCR<\/scp>\n                    ) Human Autoantibodies on Muscle Regeneration in Mice"],"prefix":"10.1002","volume":"72","author":[{"given":"Sarah","family":"Julien","sequence":"first","affiliation":[{"name":"Univ Rouen Normandie, INSERM, U1234, F\u201076000  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honorine","family":"Tomasevic","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, INSERM, U1234, F\u201076000  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thara","family":"Jaworski","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, INSERM, U1234, F\u201076000  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachid","family":"Zoubairi","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, INSERM, U1234, F\u201076000  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremie","family":"Martinet","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, INSERM, U1234, F\u201076000  Rouen France"},{"name":"CHU de Rouen, Laboratory of Immunology and Biotherapy, F\u201076000  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Drouot","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, INSERM, U1234, F\u201076000  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7591-307X","authenticated-orcid":false,"given":"Olivier","family":"Boyer","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, INSERM, U1234, F\u201076000  Rouen France"},{"name":"CHU de Rouen, Laboratory of Immunology and Biotherapy, F\u201076000  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2018.09.008"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-213518"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kead298"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1495415"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1447182"},{"issue":"8","key":"e_1_2_9_7_1","first-page":"2036","article-title":"Prevention of Anti\u2010HMGCR Immune\u2010Mediated Necrotising Myopathy by C5 Complement Inhibition in a Humanised Mouse Model","volume":"10","author":"Julien S.","year":"2022","journal-title":"Biomedicine"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(23)00003-6"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9051297"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2011.tb00387.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2015.tb00646.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24902"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4468"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2005.029835"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13395-018-0171-0"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13395-023-00323-1"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-020-00515-9"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0147198"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.5603\/FHC.2012.0021"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20211504"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232113380"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar1895"},{"issue":"25","key":"e_1_2_9_23_1","article-title":"In Immune\u2010Mediated Necrotising Myopathy, Anti\u2010HMGCR Antibodies Inhibit HMGCR Activity, Leading to the Sarcoplasmic Accumulation of Lipid Droplets and Myofibres Necrosis","volume":"496","author":"Giannini M.","year":"2025","journal-title":"Annals of the Rheumatic Diseases"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.09.065"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2217831120"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2024-225773"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2024-225732"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.10.054"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2024.09.009"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2315990121"}],"container-title":["Muscle &amp; Nerve"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.70016","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T17:12:49Z","timestamp":1762794769000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mus.70016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":29,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/mus.70016"],"URL":"https:\/\/doi.org\/10.1002\/mus.70016","archive":["Portico"],"relation":{},"ISSN":["0148-639X","1097-4598"],"issn-type":[{"value":"0148-639X","type":"print"},{"value":"1097-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"2024-08-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}