Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1990 Nov;86(5):1658–1663. doi: 10.1172/JCI114888

Mapping of a functional autoimmune epitope on the beta 1-adrenergic receptor in patients with idiopathic dilated cardiomyopathy.

Y Magnusson 1, S Marullo 1, S Hoyer 1, F Waagstein 1, B Andersson 1, A Vahlne 1, J G Guillet 1, A D Strosberg 1, A Hjalmarson 1, J Hoebeke 1
PMCID: PMC296916  PMID: 1700798

Abstract

The presence and properties of serum autoantibodies against beta-adrenergic receptors in patients with idiopathic dilated cardiomyopathy were studied using synthetic peptides derived from the predicted sequences of the human beta-adrenergic receptors. Peptides corresponding to the sequences of the second extracellular loop of the human beta 1- and beta 2-adrenergic receptors were used as antigens in an enzyme immunoassay to screen sera from patients with dilated cardiomyopathy (n = 42), ischemic heart disease (n = 17), or healthy blood donors (n = 34). The sera of thirteen dilated cardiomyopathy patients, none of the ischemic heart disease patients, and four of the healthy controls monospecifically recognized the beta 1-peptide. Only affinity-purified antibodies of these patients had a inhibitory effect on radioligand binding to the beta 1 receptor of C6 rat glioma cells. They recognized the receptor protein by immunoblot and bound in situ to human myocardial tissue. We conclude that a subgroup of patients with idiopathic dilated cardiomyopathy have in their sera autoantibodies specifically directed against the second extracellular loop of the beta 1-adrenergic receptor. These antibodies could serve as a marker of an autoimmune response with physiological and/or pathological implications.

Full text

PDF
1658

Images in this article

1660Image
on p.1660
1660Image
on p.1660
1661Image
on p.1661
1661Image
on p.1661

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bristow M. R., Ginsburg R., Umans V., Fowler M., Minobe W., Rasmussen R., Zera P., Menlove R., Shah P., Jamieson S. Beta 1- and beta 2-adrenergic-receptor subpopulations in nonfailing and failing human ventricular myocardium: coupling of both receptor subtypes to muscle contraction and selective beta 1-receptor down-regulation in heart failure. Circ Res. 1986 Sep;59(3):297–309. doi: 10.1161/01.res.59.3.297. [DOI] [PubMed] [Google Scholar]
  2. Bristow M. R., Hershberger R. E., Port J. D., Minobe W., Rasmussen R. Beta 1- and beta 2-adrenergic receptor-mediated adenylate cyclase stimulation in nonfailing and failing human ventricular myocardium. Mol Pharmacol. 1989 Mar;35(3):295–303. [PubMed] [Google Scholar]
  3. Cervantes-Olivier P., Delavier-Klutchko C., Durieu-Trautmann O., Kaveri S., Desmandril M., Strosberg A. D. The beta 2-adrenergic receptors of human epidermoid carcinoma cells bear two different types of oligosaccharides which influence expression on the cell surface. Biochem J. 1988 Feb 15;250(1):133–143. doi: 10.1042/bj2500133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Clément J. M., Szmelcman S., Jehanno M., Martineau P., Schwartz O., Hofnung M. Propriétés neutralisantes pour le virus HIV d'une protéine hybride Ma1E-CD4 exprimée chez E. coli et purifiable en une étape. C R Acad Sci III. 1989;308(14):401–406. [PubMed] [Google Scholar]
  5. Dixon R. A., Sigal I. S., Candelore M. R., Register R. B., Scattergood W., Rands E., Strader C. D. Structural features required for ligand binding to the beta-adrenergic receptor. EMBO J. 1987 Nov;6(11):3269–3275. doi: 10.1002/j.1460-2075.1987.tb02645.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Emorine L. J., Marullo S., Delavier-Klutchko C., Kaveri S. V., Durieu-Trautmann O., Strosberg A. D. Structure of the gene for human beta 2-adrenergic receptor: expression and promoter characterization. Proc Natl Acad Sci U S A. 1987 Oct;84(20):6995–6999. doi: 10.1073/pnas.84.20.6995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fraser C. M. Site-directed mutagenesis of beta-adrenergic receptors. Identification of conserved cysteine residues that independently affect ligand binding and receptor activation. J Biol Chem. 1989 Jun 5;264(16):9266–9270. [PubMed] [Google Scholar]
  8. Frielle T., Collins S., Daniel K. W., Caron M. G., Lefkowitz R. J., Kobilka B. K. Cloning of the cDNA for the human beta 1-adrenergic receptor. Proc Natl Acad Sci U S A. 1987 Nov;84(22):7920–7924. doi: 10.1073/pnas.84.22.7920. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Goodwin J. F. Mechanisms in cardiomyopathies. J Mol Cell Cardiol. 1985 Jul;17 (Suppl 2):5–9. doi: 10.1016/0022-2828(85)90003-3. [DOI] [PubMed] [Google Scholar]
  10. Homburger V., Lucas M., Rosenbaum E., Vassent G., Bockaert J. Presence of both beta1- and beta2-adrenergic receptors in a single cell type. Mol Pharmacol. 1981 Nov;20(3):463–469. [PubMed] [Google Scholar]
  11. Hopp T. P., Woods K. R. Prediction of protein antigenic determinants from amino acid sequences. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3824–3828. doi: 10.1073/pnas.78.6.3824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kobilka B. K., Dixon R. A., Frielle T., Dohlman H. G., Bolanowski M. A., Sigal I. S., Yang-Feng T. L., Francke U., Caron M. G., Lefkowitz R. J. cDNA for the human beta 2-adrenergic receptor: a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor. Proc Natl Acad Sci U S A. 1987 Jan;84(1):46–50. doi: 10.1073/pnas.84.1.46. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  14. Limas C. J., Goldenberg I. F., Limas C. Autoantibodies against beta-adrenoceptors in human idiopathic dilated cardiomyopathy. Circ Res. 1989 Jan;64(1):97–103. doi: 10.1161/01.res.64.1.97. [DOI] [PubMed] [Google Scholar]
  15. Magnusson Y., Höyer S., Lengagne R., Chapot M. P., Guillet J. G., Hjalmarson A., Strosberg A. D., Hoebeke J. Antigenic analysis of the second extra-cellular loop of the human beta-adrenergic receptors. Clin Exp Immunol. 1989 Oct;78(1):42–48. [PMC free article] [PubMed] [Google Scholar]
  16. Marullo S., Delavier-Klutchko C., Eshdat Y., Strosberg A. D., Emorine L. Human beta 2-adrenergic receptors expressed in Escherichia coli membranes retain their pharmacological properties. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7551–7555. doi: 10.1073/pnas.85.20.7551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Oldstone M. B. Molecular mimicry and autoimmune disease. Cell. 1987 Sep 11;50(6):819–820. doi: 10.1016/0092-8674(87)90507-1. [DOI] [PubMed] [Google Scholar]
  18. Rothbard J. B., Taylor W. R. A sequence pattern common to T cell epitopes. EMBO J. 1988 Jan;7(1):93–100. doi: 10.1002/j.1460-2075.1988.tb02787.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sanderson J. E., Koech D., Iha D., Ojiambo H. P. T-lymphocyte subsets in idiopathic dilated cardiomyopathy. Am J Cardiol. 1985 Mar 1;55(6):755–758. doi: 10.1016/0002-9149(85)90151-1. [DOI] [PubMed] [Google Scholar]
  20. Schultheiss H. P., Schwimmbeck P., Bolte H. D., Klingenberg M. The antigenic characteristics and the significance of the adenine nucleotide translocator as a major autoantigen to antimitochondrial antibodies in dilated cardiomyopathy. Adv Myocardiol. 1985;6:311–327. [PubMed] [Google Scholar]
  21. Sterin-Borda L., Cremaschi G., Pascual J., Genaro A., Borda E. Alloimmune IgG binds and modulates cardiac beta-adrenoceptor activity. Clin Exp Immunol. 1984 Oct;58(1):223–228. [PMC free article] [PubMed] [Google Scholar]
  22. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tzartos S. J., Seybold M. E., Lindstrom J. M. Specificities of antibodies to acetylcholine receptors in sera from myasthenia gravis patients measured by monoclonal antibodies. Proc Natl Acad Sci U S A. 1982 Jan;79(1):188–192. doi: 10.1073/pnas.79.1.188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. WILKINSON G. N. Statistical estimations in enzyme kinetics. Biochem J. 1961 Aug;80:324–332. doi: 10.1042/bj0800324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Witholt B., Boekhout M., Brock M., Kingma J., Heerikhuizen H. V., Leij L. D. An efficient and reproducible procedure for the formation of spheroplasts from variously grown Escherichia coli. Anal Biochem. 1976 Jul;74(1):160–170. doi: 10.1016/0003-2697(76)90320-1. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES