title: Cellular autoimmunity to cardiac myosin in patients with a recent myocardial infarction.
abstract: After a large myocardial infarction (MI) a progressive remodeling process can occur that results in a severe mechanical dysfunction of the heart. Among the determinants of remodeling, immune mediated inflammation has been suggested as an important contributor. However, the role of autoimmunity to cardiac antigens that are released to the circulation has not been sufficiently addressed. Cardiac myosin is a contractile protein that is unique to the myocardium and has been shown to induce a humoral immune response in patients after MI, and to trigger an autoimmune myocarditis in experimental rats and mice. In the current study, we evaluated humoral and cellular immune responses to myosin in patients with and without a history of recent MI. Eighteen patients with MI, 2 weeks to 4 months prior to initiation of the study, and eighteen control subjects were enrolled. Peripheral blood mononuclear cells (PMBC) were obtained and subjected to priming with different concentrations of cardiac myosin. Interferon-gamma and TNF-alpha were measured in conditioned medium obtained from the cultured PMBC upon priming with cardiac myosin. Humoral immune responses were also assessed by evaluating IgG anti-myosin antibodies. We have found that a third of the patients with the recent history of MI and none of the control subjects had a proliferative response to cardiac myosin evident by stimulation indices greater than 1.5. No differences were detected between the patients and controls with regard to IFN-gamma and TNF-alpha secreted by their PMBC, nor were there differences in the serum levels of IgG anti-myosin antibodies. Thus, in patients with a recent history of MI, cellular autoimmunity to cardiac myosin is present as compared with controls. It remains to be determined whether this autoimmune response is associated with an adverse outcome.
authors.affiliation: Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Miriam
authors.initials: M
authors.lastname: Moraru
authors.forename: Arie
authors.initials: A
authors.lastname: Roth
authors.forename: Gad
authors.initials: G
authors.lastname: Keren
authors.forename: Jacob
authors.initials: J
authors.lastname: George
mesh_terms: D015551:Autoimmunity; D024722:Cardiac Myosins / Q000276:immunology*; D016022:Case-Control Studies; D002465:Cell Movement / Q000276:immunology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000276:immunology / Q000503:physiopathology*; D009206:Myocardium / Q000166:cytology / Q000276:immunology*
chemical_list: D024722:Cardiac Myosins