title: Subclass specificity of autoantibodies against myosin in patients with idiopathic dilated cardiomyopathy: pro-inflammatory antibodies in DCM patients.
abstract: Detection of antimyosin antibodies in non-inflammatory cardiac disease undermines their disease specificity as a sensitive marker of damage in dilated cardiomyopathy (DCM) patients. Antibody subclass specificity could provide a more sensitive marker of disease and possibly discriminate the humoral autoimmune responses in different cardiac diseases. Frequency and reactivity of autoantibodies against alpha- and beta-isoforms of myosin heavy chain (mhc) were evaluated by ELISA for IgG, IgM, and subclasses IgG1, IgG2, and IgG3 in patients with DCM (NYHA III/IV, n = 82), end stage ischemic heart disease (E-IHD: NYHA III/IV, n = 62), mild ischemic heart disease (NYHA I/II, n = 27), and controls (n = 54). Autoantibodies against atrial and ventricular myosin were raised in heart failure patients compared to mild-IHD and controls but with different antigen affinities. Reactivity in E-IHD was significantly raised against (ventricular) beta-mhc compared with only mild-IHD patients, suggesting a relative increase in ventricular specific antibodies in IHD patients with a higher NYHA class. IgG subclass analysis for IgG1, IgG2, and IgG3 against alpha- and beta-mhc showed statistically raised levels of IgG3 only in DCM patients and a significantly higher reactivity of IgG2 in heart failure patients versus controls. The results demonstrate immunological heterogeneity of antimyosin antibodies developed in different clinical entities. Pro-inflammatory characteristics of IgG3 antibodies in a select group of patients with DCM may contribute to autoimmune mechanisms of injury in these patients.
authors.affiliation: National Heart and Lung Institute, Harefield Hospital, Harefield, Middlesex, UB9 6JH, United Kingdom.
authors.forename: R S
authors.initials: RS
authors.lastname: Warraich
authors.forename: M J
authors.initials: MJ
authors.lastname: Dunn
authors.forename: M H
authors.initials: MH
authors.lastname: Yacoub
mesh_terms: D001323:Autoantibodies / Q000145:classification / Q000276:immunology*; D002311:Cardiomyopathy, Dilated / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000145:classification / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007136:Immunoglobulins / Q000145:classification / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018995:Myosin Heavy Chains / Q000276:immunology; D009218:Myosins / Q000276:immunology*; D020033:Protein Isoforms / Q000276:immunology
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D020033:Protein Isoforms; D018995:Myosin Heavy Chains; D009218:Myosins