IgG subclass reactivity to human cardiac myosin in cardiomyopathy patientsis indicative of a Th1-like autoimmune disease

Studies performed in mice together with the demonstration of increased leve ls of heart-specific autoantibodies, cytokines and cytokine receptors in se ra from cardiomyopathy (CMP) patients argued for a pathogenic role of autoi mmune mechanisms in CMP. This study was designed to analyse the presence of IgG anti-heart antibodies in sera from patients suffering from hypertrophi c and dilatative forms of CMP as well as from patients with ischaemic heart disease and healthy individuals. Patients' sera were analysed for IgG reac tivity to Western-blotted extracts prepared from human epithelial and endot helial cells, heart and skeletal muscle specimens as well as from Streptoco ccus pyogenes. The IgG subclass (IgG1-4) reactivity to purified human cardi ac myosin was analysed by ELISA. While sera from CMP patients and healthy i ndividuals displayed comparable IgG reactivity to a variety of human protei ns, cardiac myosin represented the prominent antigen detected strongly and preferentially by sera from CMP patients. Pronounced IgG anti-cardiac myosi n reactivity was frequently found in sera from patients with dilatative CMP and reduced ventricular function. ELISA analyses revealed a prominent IgG2 /IgG3 anti-cardiac myosin reactivity in CMP sera, indicating a preferential Th1-like immune response. Elevated anti-cytomegalovirus, anti-enterovirus IgG titres as well as IgG reactivity to nitrocellulose-blotted S. pyogenes proteins were also frequently observed in the group of CMP patients. If fur ther work can support the hypothesis that autoreactivity to cardiac myosin represents a pathogenic factor in CMP, specific immunomodulation of this Th 1- towards a Th2-like immune response may represent a promising therapeutic strategy for CMP.