{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T12:49:28Z","timestamp":1782305368340,"version":"3.54.5"},"reference-count":48,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T00:00:00Z","timestamp":1780185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T00:00:00Z","timestamp":1780185600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["WA2474\/11\u20101"],"award-info":[{"award-number":["WA2474\/11\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["WA2474\/14\u20101"],"award-info":[{"award-number":["WA2474\/14\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012681","name":"Universit\u00e4tsklinikum K\u00f6ln","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012681","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac desmosome disease, as more than 50% of affected patients carry pathogenic variants in desmosome protein\u2010coding genes. In this study, we focused on the role and mechanisms of pathogenic and non\u2010pathogenic autoantibodies against intercalated disc (ICD) proteins such as desmoglein2 (DSG2) in ACM patients, healthy relatives (HR), and murine ACM models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>IgG fractions from ACM patients, HR, healthy controls, and murine ACM models were isolated. Besides ELISA and cleavage assay, dissociation assay, immunostaining, Triton\u2010X\u2010100 assay, Western blots, and atomic force microscopy were performed in murine cardiac slices, HL\u20101 cells, or induced pluripotent stem cells\u2010derived cardiomyocytes (hiPSC\u2010CMs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>IgG fractions from ACM patients and HR, but not murine ACM model\u2010derived or grouped healthy controls IgG (G\u2010HC), revealed positive ICD staining. Three out of six ACM patients derived IgGs that reduced cardiomyocyte cohesion. Pathogenic autoantibodies, bound to DSG2 in healthy and ACM hiPSC\u2010CMs, cleaved and reduced DSG2 interaction at the molecular level. We investigated GSK\u20103\u03b2 contribution to the cardiomyocyte cohesion loss and observed GSK\u20103\u03b2 reduced baseline cohesion in cultured cardiomyocytes and cardiac slices. Among five ACM\u2010IgGs, three HR\u2010IgGs tested, three pathogenic ACM\u2010IgGs activated GSK\u20103\u03b2 upstream of p38MAPK, leading to phosphorylation and junctional loss of \u03b2\u2010catenin. GSK\u20103\u03b2 inhibition rescued the loss of cell cohesion in ACM hiPSC\u2010CMs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pathogenic autoantibodies targeting DSG2 are present in ACM patients and impair cardiomyocyte cohesion in a GSK\u20103\u03b2\u2010dependent manner. In contrast, autoantibodies are absent in murine ACM models and are non\u2010pathogenic in some patients and HR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apha.70254","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T03:24:57Z","timestamp":1780284297000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Autoantibodies in Patients With Arrhythmogenic Cardiomyopathy Activate\n                    <scp>GSK<\/scp>\n                    \u20103\u03b2, Resulting in a Loss of Cardiomyocyte Cohesion"],"prefix":"10.1111","volume":"242","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1891-5161","authenticated-orcid":false,"given":"Soumyata","family":"Pathak","sequence":"first","affiliation":[{"name":"Vegetative Anatomy, Institute of Anatomy, LMU Medizin Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstanze","family":"Stangner","sequence":"additional","affiliation":[{"name":"Vegetative Anatomy, Institute of Anatomy, LMU Medizin Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Kempf","sequence":"additional","affiliation":[{"name":"Vegetative Anatomy, Institute of Anatomy, LMU Medizin Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sina","family":"Moztarzadeh","sequence":"additional","affiliation":[{"name":"Vegetative Anatomy, Institute of Anatomy, LMU Medizin Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Hiermaier","sequence":"additional","affiliation":[{"name":"Vegetative Anatomy, Institute of Anatomy, LMU Medizin Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Wider","sequence":"additional","affiliation":[{"name":"Vegetative Anatomy, Institute of Anatomy, LMU Medizin Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlene","family":"Rauschmayer","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Human Biology and BioImaging LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Williams","sequence":"additional","affiliation":[{"name":"Comprehensive Heart Failure Center and Department of Medicine I University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Stengl","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Human Biology and BioImaging LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Gerull","sequence":"additional","affiliation":[{"name":"Comprehensive Heart Failure Center and Department of Medicine I University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Biller","sequence":"additional","affiliation":[{"name":"ARVC\u2010Selbsthilfe e.V. 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