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. 1999 Oct;107(Suppl 5):749–752. doi: 10.1289/ehp.99107s5749

Linking iodine with autoimmune thyroiditis.

N R Rose 1, L Rasooly 1, A M Saboori 1, C L Burek 1
PMCID: PMC1566262  PMID: 10502541

Abstract

A great deal of circumstantial evidence has linked iodine with the rising incidence of autoimmune thyroiditis in the United States. In our investigations, we have shown directly that T cells from humans with chronic lymphocytic thyroiditis proliferate in the presence of iodinated but not in the presence of noniodinated human thyroglobulin. Moreover, the proliferative response is restored when the thyroglobulin is iodinated artificially in vitro. Using a panel of monoclonal antibodies, we found evidence that the presence of iodine induces a number of stereochemical changes in the conformation of the molecule, resulting in the loss of some antigenic determinants and the appearance of others. One prominent determinant was associated with the iodine-containing amino acid thyroxine. Both the number and position of the iodine substituents determine the precise specificity of this epitope. A new model for the study of the role of iodine in inducing thyroid autoimmunity has become available in the form of the nonobese diabetic (NOD)-H2(h4) mouse. This animal develops autoimmune thyroiditis spontaneously but in relatively low prevalence. However, if iodine is added to the drinking water, the prevalence and severity of the thyroid lesions increase markedly. The immune response is specific for thyroglobulin, both in terms of the antibody response and T-cell proliferation. In fact, the appearance of lesions can be predicted by the presence of thyroglobulin-specific IgG2b antibody. The disease, moreover, can be transferred adoptively, using spleen cells from iodine-fed donors treated in vitro with iodinated thyroglobulin. The effects of iodine feeding are greater in conventional animals compared with those maintained under specific pathogen-free conditions. Based on T-cell proliferation, it appears that the NOD-H2(h4) strain of mice has innately a greater response to murine thyroglobulin than do other mouse strains and that the proliferation is increased even more by feeding iodine. We suggest, therefore, that the presence of iodine increases the autoantigenic potency of thyroglobulin, a major pathogenic antigen in the induction of autoimmune thyroiditis. This animal model provides a unique opportunity for investigating in detail the mechanisms by which an environmental agent can trigger a pathogenic autoimmune response in a susceptible host.

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Selected References

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  1. Braverman L. E. Effects of iodine on thyroid function in man. Trans Am Clin Climatol Assoc. 1991;102:143–152. [PMC free article] [PubMed] [Google Scholar]
  2. Braverman L. E., Ingbar S. H., Vagenakis A. G., Adams L., Maloof F. Enhanced susceptibility to iodide myxedema in patients with Hashimoto's disease. J Clin Endocrinol Metab. 1971 Apr;32(4):515–521. doi: 10.1210/jcem-32-4-515. [DOI] [PubMed] [Google Scholar]
  3. Bresler H. S., Burek C. L., Hoffman W. H., Rose N. R. Autoantigenic determinants on human thyroglobulin. II. Determinants recognized by autoantibodies from patients with chronic autoimmune thyroiditis compared to autoantibodies from healthy subjects. Clin Immunol Immunopathol. 1990 Jan;54(1):76–86. doi: 10.1016/0090-1229(90)90007-d. [DOI] [PubMed] [Google Scholar]
  4. Bresler H. S., Burek C. L., Rose N. R. Autoantigenic determinants on human thyroglobulin. I. Determinant specificities of murine monoclonal antibodies. Clin Immunol Immunopathol. 1990 Jan;54(1):64–75. doi: 10.1016/0090-1229(90)90006-c. [DOI] [PubMed] [Google Scholar]
  5. Gavaret J. M., Dème D., Nunez J., Salvatore G. Sequential reactivity of tyrosyl residues of thyroglobulin upon iodination catalyzed by thyroid peroxidase. J Biol Chem. 1977 May 25;252(10):3281–3285. [PubMed] [Google Scholar]
  6. Hay I. D. Thyroiditis: a clinical update. Mayo Clin Proc. 1985 Dec;60(12):836–843. doi: 10.1016/s0025-6196(12)64789-2. [DOI] [PubMed] [Google Scholar]
  7. Jacobson D. L., Gange S. J., Rose N. R., Graham N. M. Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin Immunol Immunopathol. 1997 Sep;84(3):223–243. doi: 10.1006/clin.1997.4412. [DOI] [PubMed] [Google Scholar]
  8. Konno N., Makita H., Yuri K., Iizuka N., Kawasaki K. Association between dietary iodine intake and prevalence of subclinical hypothyroidism in the coastal regions of Japan. J Clin Endocrinol Metab. 1994 Feb;78(2):393–397. doi: 10.1210/jcem.78.2.8106628. [DOI] [PubMed] [Google Scholar]
  9. Lamas L., Ingbar S. H. The effect of varying iodine content on the susceptibility of thyroglobulin to hydrolysis by thyroid acid protease. Endocrinology. 1978 Jan;102(1):188–197. doi: 10.1210/endo-102-1-188. [DOI] [PubMed] [Google Scholar]
  10. Oddie T. H., Fisher D. A., McConahey W. M., Thompson C. S. Iodine intake in the United States: a reassessment. J Clin Endocrinol Metab. 1970 May;30(5):659–665. doi: 10.1210/jcem-30-5-659. [DOI] [PubMed] [Google Scholar]
  11. Rasooly L., Burek C. L., Rose N. R. Iodine-induced autoimmune thyroiditis in NOD-H-2h4 mice. Clin Immunol Immunopathol. 1996 Dec;81(3):287–292. doi: 10.1006/clin.1996.0191. [DOI] [PubMed] [Google Scholar]
  12. Rasooly L., Rose N. R., Saboori A. M., Ladenson P. W., Burek C. L. Iodine is essential for human T cell recognition of human thyroglobulin. Autoimmunity. 1998;27(4):213–219. doi: 10.3109/08916939808993833. [DOI] [PubMed] [Google Scholar]
  13. Rawitch A. B., Chernoff S. B., Litwer M. R., Rouse J. B., Hamilton J. W. Thyroglobulin structure-function. The amino acid sequence surrounding thyroxine. J Biol Chem. 1983 Feb 25;258(4):2079–2082. [PubMed] [Google Scholar]
  14. Roitt I. M., Cooke A. The role of autoantigen in autoimmunity. Immunol Lett. 1987 Dec;16(3-4):259–263. doi: 10.1016/0165-2478(87)90155-6. [DOI] [PubMed] [Google Scholar]
  15. Rose N. R. Autoimmune diseases: tracing the shared threads. Hosp Pract (1995) 1997 Apr 15;32(4):147–154. doi: 10.1080/21548331.1997.11443469. [DOI] [PubMed] [Google Scholar]
  16. Rose N. R. The role of infection in the pathogenesis of autoimmune disease. Semin Immunol. 1998 Feb;10(1):5–13. doi: 10.1006/smim.1997.0100. [DOI] [PubMed] [Google Scholar]
  17. Roti E., Minelli R., Gardini E., Bianconi L., Gavaruzzi G., Ugolotti G., Neri T. M., Braverman L. E. Iodine-induced subclinical hypothyroidism in euthyroid subjects with a previous episode of amiodarone-induced thyrotoxicosis. J Clin Endocrinol Metab. 1992 Nov;75(5):1273–1277. doi: 10.1210/jcem.75.5.1331165. [DOI] [PubMed] [Google Scholar]
  18. Saboori A. M., Rose N. R., Bresler H. S., Vladut-Talor M., Burek C. L. Iodination of human thyroglobulin (Tg) alters its immunoreactivity. I. Iodination alters multiple epitopes of human Tg. Clin Exp Immunol. 1998 Aug;113(2):297–302. doi: 10.1046/j.1365-2249.1998.00643.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Saboori A. M., Rose N. R., Bresler H. S., Vladut-Talor M., Burek C. L. Iodination of human thyroglobulin (Tg) alters its immunoreactivity. I. Iodination alters multiple epitopes of human Tg. Clin Exp Immunol. 1998 Aug;113(2):297–302. doi: 10.1046/j.1365-2249.1998.00643.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Saboori A. M., Rose N. R., Burek C. L. Iodination of human thyroglobulin (Tg) alters its immunoreactivity. II. Fine specificity of a monoclonal antibody that recognizes iodinated Tg. Clin Exp Immunol. 1998 Aug;113(2):303–308. doi: 10.1046/j.1365-2249.1998.00644.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Saboori A. M., Rose N. R., Burek C. L. Iodination of human thyroglobulin (Tg) alters its immunoreactivity. II. Fine specificity of a monoclonal antibody that recognizes iodinated Tg. Clin Exp Immunol. 1998 Aug;113(2):303–308. doi: 10.1046/j.1365-2249.1998.00644.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sundick R. S., Bagchi N., Brown T. R. The role of iodine in thyroid autoimmunity: from chickens to humans: a review. Autoimmunity. 1992;13(1):61–68. doi: 10.3109/08916939209014636. [DOI] [PubMed] [Google Scholar]
  23. Tajiri J., Higashi K., Morita M., Umeda T., Sato T. Studies of hypothyroidism in patients with high iodine intake. J Clin Endocrinol Metab. 1986 Aug;63(2):412–417. doi: 10.1210/jcem-63-2-412. [DOI] [PubMed] [Google Scholar]
  24. Vladutiu A. O., Rose N. R. Autoimmune murine thyroiditis relation to histocompatibility (H-2) type. Science. 1971 Dec 10;174(4014):1137–1139. doi: 10.1126/science.174.4014.1137. [DOI] [PubMed] [Google Scholar]
  25. Weatherall D., Sarvetnick N., Shizuru J. A. Genetic control of diabetes mellitus. Diabetologia. 1992 Dec;35 (Suppl 2):S1–S7. doi: 10.1007/BF00586273. [DOI] [PubMed] [Google Scholar]
  26. Weaver D. K., Batsakis J. G., Nishiyama R. H. Relationship of iodine to "lymphocytic goiters". Arch Surg. 1969 Feb;98(2):183–186. doi: 10.1001/archsurg.1969.01340080075014. [DOI] [PubMed] [Google Scholar]

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