Autoantibodies to thyroglobulin in health and disease |
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Authors: | Noel R Rose C Lynne Burek |
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Institution: | (1) Department of Pathology and Department of Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, MD |
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Abstract: | Thyroglobulin (Tg)—a heavily glycosylated, iodinated protein—isa major autoantigen in autoimmune thyroiditis. Tg also induces
thyroiditis by immunization of experimental animals. Humans with chronic lymphocytic thyroiditis characteristically produce
autoantibodies to thyroglobu lin, but similar autoantibodies are also found in some clinically normal, euthyroid individuals.
A comparison of the fine specificity of autoantibodies in humans and in experimentally immunized mice was carried out, based
on their ability to inhibit a panel of monoclonal antibodies (MAbs). Patients with autoimmune thyroid disease, as well as
normal individuals, produced autoantibodies mainly to the conserved, cross-reactive determinants of thyroglobulin. Patients
developed additional autoantibodies to species-restricted epitopes. The determinants recognized by patients with Graves' disease
differed in some respects from epitopes recognized by thyroiditis patients or patients with differentiated thyroid carcinoma.
Similarly, mice that are genetically susceptible to thyroiditis produced autoantibodies that reacted with the mouse-specific
antigenic determinants. Using an autoantibody that reacts with one of the epitopes associated with thyroiditis, a reactive
15-k Da fragment of human Tg—localized at the carboxy end of the molecule—was isolated and sequenced. Iodine plays an important
role in the precise specificity of the disease-associated epitope, since T cells from patients with thyroiditis react with
iodinated but not noniodinated human thyroglobulin. Addition of iodine to Tg generates new or cryptic epitopes. Use of a selected
MAb as a surrogate for the T-cell receptor suggests that a specific iodine-containing epitope is sometimes involved in recognition.
Finally, thyroglobulin-reactive autoantibodies exhibit proteolytic activity on thyroglobulin. |
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Keywords: | Thyroglobulin iodine thyroiditis autoimmune disease autoimmunity autoantigen thyroxine |
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