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Background  Autoantibodies against the second extracellular loop of the β 1 -adrenergic receptor (β 1 -AA) not only contribute to increased susceptibility to heart failure, but also play a causative role in myocardial remodeling through their sympathomimetic-like effects that are induced upon binding to the β 1 -adrenergic receptor. However, their role in the function of T lymphocytes has never been previously investigated. Our present study was designed to determine whether β 1 -AA isolated from the sera of dilated cardiomyopathy (DCM) patients caused the proliferation of T cells and the secretion of cytokines.    Methods  Blood samples were collected from 95 DCM patients as well as 95 healthy subjects, and β 1 -AA was detected using ELISA. The CD3 + T lymphocytes were selected separately through flow cytometry and the effect of β 1 -AA on T lymphocyte proliferation was examined by CCK-8 kits and CFSE assay. Western blotting was used to analyze the expressions of phospho-VASP and phospho-p38 MAPK.    Results  β 1 -AA enhanced the proliferation of T lymphocytes. This effect could be blocked by the selective β 1 -adrenergic receptor antagonist metoprolol, PKA inhibitor H89, and p38 MAPK inhibitor SB203580. Furthermore, the expression of the phosphorylated forms of phospho-VASP and phospho-p38 MAPK were markedly increased in the presence of β 1 -AA. β 1 -AA also inhibited the secretion of interferon-γ (IFN-γ) while promoting an increase in interleukin-4 (IL-4) levels.    Conclusions  These results demonstrate that β 1 -AA isolated from DCM patients binds to β 1 -AR on the surface of T cells, causing changes in T-cell proliferation and secretion through the β 1 -AR/cAMP/PKA and p38 MAPK pathways.

β1-Adrenoceptor Autoantibodies from DCM Patients Enhance the Proliferation of T Lymphocytes through the β1-AR/cAMP/PKA and p38 MAPK Pathways