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While agonistic anti-\u03b21-adrenergic receptor antibodies (anti-\u03b21AR-EC\n                      <jats:sub>II<\/jats:sub>\n                      ) have a recognized pathogenic role in idiopathic dilated cardiomyopathy (DCM), the relevance of HRA in gCMP remains unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      One hundred gCMP patients with confirmed genetic variants in cardiomyopathy genes were compared with 100 age- and sex-matched healthy individuals. Antibody reactivities were quantified using bead-based flow cytometric assays against cardiac antigens: The second extracellular loop of the \u03b21 adrenergic receptor (\u03b21AR-EC\n                      <jats:sub>II<\/jats:sub>\n                      ), Troponin I3 (TPI3), Tropomyosin 1 (TPM1), Myosin heavy chain 6 and 7 (MYH6, MYH7) and Myosin light chain 7 (MYL7).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>gCMP patients showed higher anti-TPI3 and lower anti-TPM1 antibody levels compared to controls indicating increased induction of the former and loss of the latter in gCMP patients. Age and sex influenced HRA patterns in both groups. Anti-MYH6 and anti-TPM1 antibody levels were negatively associated with left ventricular ejection fraction (LVEF), both overall and within specific gCMP subtypes, including hypertrophic and arrhythmogenic cardiomyopathy. Additionally, anti-MYH6 antibody levels were negatively associated with right ventricular function, measured by tricuspid annular plane systolic excursion (TAPSE).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings stress the diagnostic potential of HRA profiling and indicate that gCMP patients might profit from therapeutic targeting of HRA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12872-026-06808-3","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:05:10Z","timestamp":1792674310000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Heart-reactive antibody levels differentially associate with ventricular function in hereditary cardiomyopathies"],"prefix":"10.1186","volume":"26","author":[{"given":"Dennis","family":"Schiffer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boshra","family":"Afshar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Grosser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Pet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Schmidbauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Bauser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Boivin-Jahns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Jahns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Frantz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Heuschmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"St\u00f6rk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Gerull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Beyersdorf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Morbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"key":"6808_CR1","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1056\/NEJM200012073432304","volume":"343","author":"M Kamisago","year":"2000","unstructured":"Kamisago M, Sharma SD, DePalma SR, et al. 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The study protocol was conducted in accordance with the Declaration of Helsinki. The study involving patients with genetic cardiomyopathy (gCMP) was approved by the Ethics Committee of the Medical Faculty, Julius Maximilians University, W\u00fcrzburg, Germany (vote #29\/17). The STAAB study protocol was also approved by the Ethics Committee of the Medical Faculty, Julius Maximilians University, W\u00fcrzburg, Germany (vote #98\/13). Written informed consent for publication was obtained from all participants.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"D. Schiffer: received travel grants from Alnylam Pharmaceuticals. C. Morbach: reports a research cooperation between the University of W\u00fcrzburg and Tomtec Imaging Systems funded by a research grant from the Bavarian Ministry of Economic Affairs, Regional Development and Energy, German Germany (MED-1811-0011, LSM-2104-0002, and LSM-2403-0005);. She further received advisory and speakers honoraria as well as travel grants from Tomtec, Edwards, Alnylam, Pfizer, Boehringer Ingelheim, Eli Lilly, AstraZeneca, Novo Nordisk, Alexion, Janssen, Bayer, Intellia, Bristol Myers Squibb and Cytokinetics; she serves as principal investigator in trials sponsored by Alnylam, Bayer, Novo Nordisk, Intellia and AstraZeneca. B. Gerull: received advisory and speakers honoraria from Alnylam, Chiesi, Boehringer Ingelheim Pharma and BMS and is a principal investigator of a clinical trial sponsored by Tenaya.","order":2,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"964"}}