Thyroid injury, autoantigen availability, and the initiation of autoimmune thyroiditis

Iodine depletion prevents disease and iodine repletion, which may cause thyroid cell injury by reactive oxygen intermediates, initiates disease in the Obese Strain chicken model of spontaneous autoimmune thyroiditis (AT). To examine the role of cell injury and autoantigen availability in AT induction we compared the immune responses that followed blunt trauma to the OS thyroid in the absence of iodine and the administration of normal dietary iodine in the absence of thyroid injury. Serum thyroglobulin concentrations were elevated following thyroid injury and the extensive thyroid infiltrates had high macrophage/CD4 + , CD8 + , B cell ratios consistent with an acute inflammatory response. The response was self limiting and undetectable in all animals 2 weeks later. Birds raised on a similar low iodine regimen were withdrawn from the regimen and given normal dietary iodine. Their thyroids showed no evidence of acute ultrastructural damage. The resulting early thyroid infiltrates had low macrophage/CD4 + , CD8 + , B cell ratios. Two weeks later these animals showed severe thyroid infiltration (43%) and after 4 weeks all animals had >90% infiltration. Thus, the presence or absence of thyroidal iodine, whether accompanied by injury or not, determined the nature and consequence of the immune response which argues against hypotheses that include obligatory injury at disease onset. Taken with previous work, this study suggests that iodination of an autoreactive thyroglobulin epitope is a requisite pathogenic action of iodine and supports the notion that in some organ-specific autoimmunity, a component of the dysregulation is associated with aberrant activity of the target tissue.