Anti-heart autoantibodies in familial dilated cardiomyopathy.
ABSTRACT Familial aggregation is a feature of myocarditis and dilated cardiomyopathy (DCM). Myocarditis, a clinically polymorphic inflammatory disease of the myocardium, is diagnosed by endomyocardial biopsy (EMB) and may lead to DCM. Mutations in several genes encoding myocyte structural proteins are known monogenic DCM causes, but because of high etiologic and genetic heterogeneity, the gene defects identified so far account for a minority of cases. In the last decade, it has been discovered that autoimmunity plays a pivotal role in myocarditis and DCM that are thought to represent different stages of an organ-specific autoimmune disease in genetically predisposed individuals. None of the available genetic studies in familial DCM has taken into account the autoimmune phenotype markers in the characterization of index patients and relatives, thus it is not known whether or not the described gene defects are involved in the autoimmune form of the disease. In animal models autoimmune myocarditis/DCM can be induced by viral infection, immunization with heart-specific autoantigens, or develop spontaneously in genetically predisposed strains. It may be cell or antibody-mediated; susceptibility is based upon multiple MHC and non-MHC genes. In patients, the diagnosis of autoimmune myocarditis/DCM requires exclusion of viral genome on EMB and detection of serum heart-reactive autoantibodies. They are found in index patients and relatives from about 60% of both familial and non-familial pedigrees and predict DCM development among healthy relatives. Some antibodies have functional effects on cardiac myocytes in vitro, in animal models and possibly in a DCM subset without inflammation, responsive to extracorporeal immunoadsorption. Cardiac-specific autoantibodies, which are shown to be disease-specific for myocarditis/DCM, can be used as biomarkers for identifying patients in whom, in the absence of active infection of the myocardium, immunosuppression and/or immunomodulation may be beneficial and their relatives at risk. Future studies should clarify genetic basis of human autoimmune myocarditis/DCM as well as genotype/immune phenotype correlations.
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ABSTRACT: Cardiomyopathy is a major cause of sudden unexpected death in young patients, it contributes significantly to the societal burden of heart failure. Now significant evidences from animal models and clinical studies suggests that viral myocarditis is important in the etiology of dilated cardiomyopathy. Enterovirus, and especially Coxsackieviruses of group B (CVB), is the most common infectious agent [1, 2]. Enteroviruses (family Picornaviridae) are nonenveloped icosahedral viruses that contain a single plus-strand RNA genome of about 7,500bp. The CVB are typical enteroviruses and 5' end of the genome is not capped but is linked covalently to the viral protein, VPg. The virus receptor, human coxsackievirus and adenovirus receptor (CAR), a protein of the immunoglobulin superfamily [3-5], most likely interacts with virus capsid in the depression that surrounds the 5-fold axes of symmetry.
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ABSTRACT: Growing evidence indicates a cardio-pathogenic role of autoantibodies against β1-adrenergic receptors (β1AR). In particular autoantibodies stimulating β1AR-mediated cAMP-production (i.e. agonistic β1AR autoantibodies) play a paramount role in chronic heart failure. When induced by immunisation, such autoantibodies cause heart failure in rodents; when present in patients they negatively affect survival in heart failure. However, the true prevalence and clinical impact of agonistic β1AR autoantibodies in human heart disease are still unclear, as are the events triggering their production, and the inter-relationship between autoantibody level and disease activity. β1AR autoantibodies can be removed by extracorporeal absorption or neutralised by systemic administration of synthetic epitope mimics. Only patients bearing agonistic β1AR autoantibodies in their bloodstream will benefit from these approaches. Therefore, reliable detection of agonistic β1AR autoantibodies is a key pre-requisite for the future implementation of these strategies. β1AR autoantibodies impact on conformation and down-stream signalling of the receptor by binding a conformational epitope, which is poorly represented by synthetic mimics and readily destroyed by fixation. Consequently, β1AR autoantibodies can reliably be detected only by assays utilising the native β1AR as a test antigen. To provide a sufficient basis for diagnostic predictions or therapeutic decisions, one must also determine whether β1AR autoantibodies stimulate the receptor, which again requires native, cell-based reporter systems. Translation of these procedures into versatile diagnostic tests fitting the requirements of general health care is a challenge for future development. Here, we will review the state of diagnostic and therapeutic efforts in the field of β1AR-directed autoimmunity, thereby aiming to furnish a conceptual frame for the further development of novel, more reliable diagnostic tools and more specific antibody-targeted therapeutic concepts.Autoimmunity reviews. 08/2014;
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ABSTRACT: Systemic lupus erythematosus is an inflammatory disorder of autoimmune origin that can involve multiple organs. Cardiac compromise can occur in patients with established disease, or it can be the initial manifestation in some of these patients. The heart commitment in this disorder can vary in their severity until producing life-threatening conditions, and it can affect any structure or heart tissue. Additionally, the systemic inflammation present is associated to accelerated atherosclerosis that can evolve to early ischemic heart disease, increasing the risk of cardiovascular illness significantly when it is compared with general population. The main characteristics of heart manifestations in systemic lupus erythematosus are discussed, as well as their diagnosis and treatment.Revista Colombiana de Reumatología. 09/2013; 20(3):148-154.