Linking iodine with autoimmune thyroiditis.

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.

Environmental Modulation of Autoimmune Arthritis Involves the Spontaneous Microbial Induction of T Cell Responses to Regulatory Determinants Within Heat Shock Protein 65

“…Recently, it has been reported that hsp60 cross-reactive T cells mediate autoimmune pathology of the small intestine (29). In contrast to the above-mentioned studies (11)(12)(13)(14)(15)(16), in this study, we attribute reduced incidence and severity of, rather than induction of, AA to determinant mimicry.…”

“…In other experimental animal models of autoimmunity, the initiation and/or propagation of autoimmunity has been attributed to the conventional environment; for example, joint and intestinal inflammatory disease in HLA-B27 transgenic rats (12), iodine-induced autoimmune thyroiditis in NOD-H2 h4 mice (13), experimental autoimmune thyroiditis in rats (14), hemolytic anemia (15), experimental autoimmune encephalomyelitis (16), and Pristaneinduced arthritis (17). In contrast, the current study has revealed that exposure of a susceptible rat strain to the conventional environment rather leads to a significant reduction in the incidence and severity of an autoimmune disease, AA, through spontaneous induction of T cells against regulatory determinants of Bhsp65.…”

Pilot study of urinary iodine concentration and of biochemical thyroid parameters before and after cautious public health intervention on salt iodide content: The Swiss longitudinal 1996–2000 iodine study

“…Our favorable findings, however -no rise of average antibody titers and no rise of the percentage of titers found above the normal limit, but rather a decrease of all anti-Tg-Ab titers -contrast with data from elsewhere, where the increment in iodine supply had been steeper. Experimentally, the steep rise of iodine supply in genetically susceptible mice caused a higher occurrence of autoimmune thyroiditis and of positive anti-Tg-Ab titers in a dosedependent manner after only 8 weeks (Rose et al, 1997). In Sri Lanka, the prevalence of anti-Tg-Ab was found markedly raised (14.3-69.7%) in 367 schoolgirls aged 11-16 y, after commercial salt had been iodized at a variable degree in 1993 (Premawardhana et al, 2000).…”

Evidence for the role of environmental agents in the initiation or progression of autoimmune conditions.

“…Autoimmune thyroiditis is characterized by lymphocytic infiltration and generation of autoantibodies that recognize thyroidrelated molecules including thyrotropin and its receptors, the Na-I symporter (rNIS), thyroglobulin, T3, and T4 (8,11,12 (Table 2).…”