Human cardiac myosin autoantibodies impair myocyte contractility: a cause-and-effect relationship

The functional relevance of autoantibodies (Abs) against cardiac myosin ( CM) in clinical idiopathic dilated cardiomyopathy (DCM) remains controversial. The study sought to determine effects of human Abs affinity-purified (AF) by immunoaffinity column chromotography on excitation-contraction coupling in isolated myocytes. Effects of CM-Abs from heart failure patients with DCM (n = 19) and ischemic heart disease (IHD, n = 19) on contractility, L-type Ca2+ current, and Ca2+ transients in continuously perfused rat ventricular myocytes were studied. Immunofluorescence studies using confocal microscopy were carried out to determine whether Abs were internalized. AF-Abs from either group did not differ in IgG titer but differed in their elution profiles. The IgG3 subclass response was higher in AF fractions from DCM (21%) than IHD (5%) patients. The Abs reduced the capacity of field-stimulated myocytes to contract in a dose-dependent manner. Inhibition of contraction, as a percentage of untreated cells, was greater with DCM than IHD-Abs ( P = 0.004), and the effect was independent of Ab titer. An increase in frequency of the beating myocytes (0.2 to 3.0 Hz) raised peak systolic and diastolic levels of [Ca2+](i) of cells treated with DCM but not IHD-Abs ( P < 0.005). The AF-Abs were not internalized by myocytes and had no effect on L-type Ca2+ currents. The altered sensitivity of the myofilaments to [Ca2+](i) by CM-Abs may represent a potential mechanism of autoantibody-mediated impairment in clinical DCM. -Warraich, R. S., Griffiths, E., Falconar, A., Pabbathi, V., Bell, C., Angelini, G., Suleiman, M.-S., Yacoub, M. H. Human cardiac myosin autoantibodies impair myocyte contractility: a cause-and-effect relationship.