Subclass specificity of autoantibodies against myosin in patients with idiopathic dilated cardiomyopathy: pro-inflammatory antibodies in DCM patients.

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. Copyright 1999 Academic Press.