{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T08:42:43Z","timestamp":1793090563460,"version":"4.5.0"},"reference-count":129,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T00:00:00Z","timestamp":1742428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Myocarditis leads to dilated cardiomyopathy (DCM) with one-third failing to recover normal ejection fraction (EF 50%). Our previous studies have supported a Th17 autoimmune pathogenesis where IL17A and IL-6 are elevated in myocarditis patients who do not recover normal EF. In the non-recovered group, autoantibody mechanisms of pathogenesis in myocardial injury and systolic dysfunction are not fully understood. Furthermore, in our myocarditis cohort, cardiac myosin (CM) autoantibodies (AAbs) were elevated and cross-reactive with the \u03b2\u2212adrenergic receptor (\u03b2AR). Here we studied cross-reactive CM\/\u03b2AR serum AAbs and human myocarditis-derived monoclonal antibodies (mAbs) to define their potential pathogenic mechanisms and to identify unique human CM epitopes associated with non-recovery in a longitudinal (n=41) cohort. Elevated CM IgG AAbs in the non-recovered phenotype correlated with reduced EF and poor outcomes. Human CM epitopes unique to the non-recovered phenotype shared strong amino acid sequence homology with extracellular loops of \u03b2ARs and supported molecular mimicry and cross-reactivity between CM and \u03b2AR. Myocarditis-derived IgG and human mAb 2C.4 activated protein kinase A (PKA) in an IgG, CM, and \u03b2AR-dependent manner in H9c2 heart myoblast cell line, and transcriptomic analysis revealed mAb 2C.4 induced fibrosis pathways which were highly similar pathways seen with isoproterenol, a beta receptor agonist. Our data translate into new mechanistic insights from our small longitudinal group of myocarditis\/DCM patients and into potential therapeutic targets and biomarkers for future studies.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1500909","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T09:41:54Z","timestamp":1742463714000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Cardiac autoantibodies promote a fibrotic transcriptome and reduced ventricular recovery in human myocarditis"],"prefix":"10.3389","volume":"16","author":[{"given":"Jennifer 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