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.
Limas
C
C
Department of Laboratory Medicine, University of Minnesota Medical School, Minneapolis 55455.
Limas
C J
CJ
Boudoulas
H
H
Graber
H
H
Bair
R
R
Sparks
L
L
Wooley
C F
CF
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