Linking Iodine with Autoimmune Thyroiditis

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Environmental Health Perspectives Volume 107, Supplement 5, October 1999]

Linking Iodine with Autoimmune Thyroiditis

Noel R. Rose,1,2 Rasooly,1 Ali M. Saboori,2 and C. Lynne Burek2

1Department of Molecular Microbiology and Immunology, 2Department of

Pathology, The s Hopkins Medical Institutions, Baltimore, land USA

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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)-H2h4 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-H2h4 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. Key words:

autoimmune disease, autoimmunity, iodine, thyroglobulin, thyroiditis,

thyronine, thyroxine, tyrosine. -- Environ Health Perspect 107(suppl

5):749-752 (1999).

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