T-cell receptor gene polymorphisms in familial cardiomyopathy: correlation with anti-beta-receptor autoantibodies.
Cardiac autoantibodies have been detected in a significant proportion of patients with dilated cardiomyopathy, but their relation to the pathogenesis of the disease remains unknown. This issue was examined in 41 members of an Ohio family with a heritable disorder of the cardiac conduction system and the myocardium. In 41.5% of all members studied, serum anti-beta-receptor antibodies were identified by a combination of techniques: ligand binding inhibition assay, enzyme-linked immunoassay of a beta 1-receptor peptide, and adenylate cyclase inhibition. The prevalence of autoantibodies was significantly higher (p < 0.01) in the affected (64.7%) than in the unaffected (25.0%) members. A 10.0 kb restriction fragment length polymorphism of the C beta region of the T-cell receptor gene was also overrepresented in affected males (60% versus 30% unaffected males, p < 0.01). In males, the presence of anti-beta-receptor antibodies was linked to the 10.0 kb C beta polymorphism. In affected males, a BlgII C alpha 2.14 kb polymorphism was also more frequent (62% versus 32% in unaffected, p < 0.01) and was linked to the presence of anti-beta-receptor antibodies. The distribution of haplotypes defined by V beta 8, C alpha, and C beta probes was significantly different between affected and unaffected (p < 0.04) and between antibody-positive and antibody-negative individuals. Since the major function of the T-cell receptor is the recognition of processed autoantigens, these results provide additional support for the role of autoimmunity in dilated cardiomyopathy.
Department of Laboratory Medicine, University of Minnesota Medical School, Minneapolis 55455.
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C
Limas
C J
CJ
Limas
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H
Boudoulas
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H
Graber
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Bair
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Sparks
C F
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Wooley
D000328:Adult; D001323:Autoantibodies / Q000378:metabolism*; D015551:Autoimmunity; D009202:Cardiomyopathies / Q000235:genetics* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005192:Family Health; D005260:Female; D005796:Genes; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*
D001323:Autoantibodies; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta