The etiology of human disease such as insulin-dependent diabetes mellitus, multiple sclerosis, idiopathic thrombocytopenic purpura, chronic aggressive hepatitis and post measles encephalitis have all been related to possible infection followed by autoimmune reactions. The availability of heart-specific autoantibodies generated in the course of Coxsackie B3 infection of certain strains of mice provides us with a unique opportunity to evaluate the oft-stated hypothesis that autoimmunity contributes significantly to post-infectious myocarditis. With these autoantibodies we can identify and isolate the target antigens and test their ability to engender an autoimmune response under experimental conditions. Initially, we will characterize the tissue reactivity of the CB3-induced autoantibodies by immunofluorescence analyses. Characterized antisera will be used in the identification of the heart specific autoantigens. These antigens will be solubilized from heart homogenates and sarcolemmal-subsarcolemmal vesicle preparations and then electrophoresed on acrylimide gels. Once identified by immunodetection of Western blotted myocardial antigens, heart specific serological reagents (i.e., xenoantiserum, alloantiserum and monoclonal antibodies) will be prepared from these enriched antigens. The reactivity of these serological reagents will be compared with the heart specific autoantibodies (antiserum and monoclonal antibodies) from CB3 infected animals. We will examine the mechanisms for initiating the post-infectious autoimmunity using these serological reagents and purified autoantigens. In vitro and in vivo experiments will determine whether an autologous antigen, a cross-reacting antigen or an anti-id antibody are the major stimuli of the post-infectious autoimmune myocarditis. Experiments will be designed to study disorders of the normal immunoregulatory mechanisms involved in autoimmune myocarditis. These investigations can be directly related to clinical post-infectious myocarditis and lead to more rational modes of prevention or treatment of these cardiopathies.
Showing the most recent 10 out of 34 publications
