Thyroid-stimulating autoantibody production in vitro

Article metrics

Abstract

GRAVES' disease is an autoimmune disorder in which hyperthyroidism is associated with the presence of thyroid-stimulating autoantibodies1. Recent work suggests that these antibodies, collectively termed TSAb, are antibodies to the thyrotrophin (TSH) receptor which stimulate the thyroid by binding to the receptor and activating adenylate cyclase1–5. Synthesis of the autoantibody in vivo may result from defects in both the thyroid and the immune system. In the case of the thyroid, this may be an aberration in the synthesis or shedding of plasma membrane components related to the TSH receptor. In the case of the immune system, a current view is that autoantibody formation is the result of a suppressor T cell defect6. An in vitro model of TSAb synthesis would permit an analysis of the role of the thyroid and the immune system in the events leading to thyroid-stimulating antibody production. Attempts have been made to study TSAb production in short-term cultures of peripheral blood lymphocytes from Graves' patients. These studies, however, did not use optimal conditions for immunoglobulin production and the levels of TSAb reported were close to the limits of detectability of the imprecise assay methods used7–11. In the study described here we have used the optimal conditions for culturing lymphocytes provided by Marbrook flasks12 in conjunction with two new sensitive and precise methods for detecting TSAb—the radio-receptor13 and cytochemical assays14,15. With this system we have readily been able to detect TSAb production in cultures of Graves' lymphocytes.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Hall, R., Rees Smith, B. & Mukhtar, E. D. Clin. Endocr. 4, 213–230 (1975).

  2. 2

    Mukhtar, E. D., Rees Smith, B., Pyle, G. A., Hall, R. & Vice, P. Lancet i, 713–720 (1975).

  3. 3

    Fayet, G. et al. FEBS Lett. 32, 299–302 (1973).

  4. 4

    Manley, S. W., Bourke, J. R. & Hawker, R. W. J. Endocr. 61, 437–445 (1974).

  5. 5

    Mehdi, S. Q. & Nussey, S. S. Biochem. J. 145, 105–111 (1975).

  6. 6

    Allison, A. C. & Denman, A. M. Br. med. Bull. 32, 124–129 (1976).

  7. 7

    McKenzie, J. M. & Gordon, J. in Current Topics in Thyroid Research (eds Cassano, C. & Andreoli, M.) 445 (Academic, New York, 1965).

  8. 8

    Miyai, K., Fukuchi, M., Kumahara, U. & Abe, H. J. clin. Endocr. Metab. 27, 855–860 (1967).

  9. 9

    Wall, J. R., Good, B. F., Forbes, I. J. & Hetzel, B. S. Clin. exp. Immun. 4, 555–561 (1973).

  10. 10

    Knox, A. J. S., von Westarp, C., Row, V. V. & Volpé, R. J. clin. Endocr. Metab. 43, 330–337 (1976).

  11. 11

    Knox, A. J. S., von Westarp, C., Row, V. V. & Volpé, R. Metabolism 25, 1217–1223 (1976).

  12. 12

    Marbrook, J. Lancet ii, 1279–1281 (1967).

  13. 13

    Rees Smith, B. & Hall, R. Lancet ii, 427–431 (1974).

  14. 14

    Bitensky, L., Alaghband-Zadeh, J. & Chayen, J. Clin. Endocr. 3, 363–374 (1974).

  15. 15

    Petersen, V., Smith, B. R. & Hall, R. J. clin. Endocr. Metab. 41, 199–202 (1975).

  16. 16

    Wu, L. Y. F., Lawton, A. R. & Cooper, M. D. J. clin. Invest. 52, 3180–3189 (1973).

  17. 17

    Janossy, G., Gomez de la Concha, E., Waxdal, M. J. & Platts-Mills, T. Clin. exp. Immun. 26, 108–117 (1976).

  18. 18

    Weinstein, Y. & Melmon, K. L. Immun. Comm. 5, 401–416 (1976).

  19. 19

    Bøyüm, A. Scand. J. Immun. 5 suppl. 5, 9–15 (1976).

  20. 20

    Wide, L., Nillius, S. J., Gemzell, C. & Roos, P. Acta Endocr. suppl. 174, 1–58 (1974).

  21. 21

    Gilbert, D. M., Besser, G. M., Bitensky, L. & Chayen, J. J. Endocr. (in the press).

  22. 22

    North, J. R. & Maizeis, R. M. Immunology 32, 771–776 (1977).

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

MCLACHLAN, S., SMITH, B., PETERSEN, V. et al. Thyroid-stimulating autoantibody production in vitro. Nature 270, 447–449 (1977) doi:10.1038/270447a0

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.