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Anti-beta-receptor antibodies in human dilated cardiomyopathy and correlation with HLA-DR antigens
1Department of Medicine (Cardiovascular Section), University of Minnesota School of Medicine, Minneapolis 55455.
Insights
Heart failure may involve antibodies against beta-adrenoceptors, particularly in dilated cardiomyopathy. Human Leukocyte Antigen (HLA)-DR4 is linked to these antibodies, suggesting a genetic component in this heart condition.
Area of Science:
- Cardiology
- Immunology
- Genetics
Background:
- The mechanisms behind reduced beta-adrenoceptor density in failing hearts are unclear.
- Heart failure pathogenesis may be influenced by the underlying cause.
- Antibodies against beta-adrenoceptors are found in some dilated cardiomyopathy patients.
Purpose of the Study:
- To investigate immunogenetic markers associated with anti-beta-receptor antibodies in dilated cardiomyopathy.
- To explore the role of the major histocompatibility locus in the development of these antibodies.
Main Methods:
- Ligand binding inhibition, immunoprecipitation, and immunoblotting assays were used to detect anti-beta-receptor antibodies.
- Human Leukocyte Antigen (HLA) phenotyping was performed on patients with dilated cardiomyopathy and alcoholic cardiomyopathy.
- Prevalence of HLA-DR4 and other HLA phenotypes was compared between patient groups and healthy subjects.
Main Results:
- A significantly higher prevalence of HLA-DR4 was observed in dilated cardiomyopathy patients compared to controls.
- HLA-DR4 was strongly associated with the presence of anti-beta-receptor antibodies in dilated cardiomyopathy.
- No significant HLA association was found in alcoholic cardiomyopathy, and fewer patients had anti-beta-receptor antibodies.
Conclusions:
- The presence of anti-beta-receptor antibodies in idiopathic dilated cardiomyopathy may be genetically influenced by the major histocompatibility locus.
- This suggests an autoimmune component in some cases of dilated cardiomyopathy.
- The findings differentiate the immunogenetic profile of dilated cardiomyopathy from alcoholic cardiomyopathy.
Abstract:
The mechanisms responsible for the decline in the density of beta-adrenoceptors in the failing myocardium have not been adequately defined. It is a possibility that the nature of the process leading to heart failure may determine, in large part, the pathogenesis of this decline. Sera of some patients with dilated cardiomyopathy contain antibodies directed against the beta-adrenoceptor, as judged by ligand binding inhibition, immunoprecipitation and immunoblotting assays. Because deranged immune function is thought to play a role in dilated cardiomyopathy, immunogenetic markers of the propensity to develop anti-beta-receptor antibodies were sought. The prevalence of HLA-DR4 was significantly higher in dilated cardiomyopathy patients (40 vs 24% in 511 normal subjects, pc less than 0.001). In contrast, no association was found between HLA phenotypes and alcoholic cardiomyopathy. Furthermore, 72% (13 of 18) of the HLA-DR4 dilated cardiomyopathy patients had anti-beta-receptor antibodies compared to 22% (7 of 33) HLA-DR4-negative patients; in the latter, presence of antibody was linked to the HLA-DR1 phenotype. Conversely, 67% (15 of 23) of the antibody-positive patients were typed as HLA-DR4 compared to only 10% of the antibody-negative patients. Interestingly, none of the 23 antibody-positive patients were typed as HLA-DR3 while 37% of the antibody-negative did. Only 25% of alcoholic cardiomyopathy patients had anti-beta-receptor antibodies and no preponderant HLA association could be demonstrated. These results suggest that the presence of anti-beta-receptor antibodies in patients with idiopathic dilated cardiomyopathy may be under the control of the major histocompatibility locus.