This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Schuppert, F. Articles by Kohn, L. D. Search for Related Content PubMed PubMed Citation Articles by Schuppert, F. Articles by Kohn, L. D.

Increased Major Histocompatibility Complex (MHC) Expression in Nontoxic Goiters Is Associated with Iodide Depletion, Enhanced Ability of the Follicular Thyroglobulin to Increase MHC Gene Expression, and Thyroid Autoantibodies

Department of Clinical Endocrinology, Hannover Medical School (F.S., D.E.), D-30625 Hannover, Germany; Department of Surgery, Essen University (A.F.), D-45122 Essen, Germany; Chair of Endocrinology, University G. D’Annunzio (G.N.), I-66100 Chieti, Italy; and Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (K.S., L.D.K.), Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Frank Schuppert, M.D., Department of Clinical Endocrinology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany.

Recent studies suggest that thyroglobulin (TG) accumulated in the follicular lumen of colloid nodular goiters can increase major histocompatibility complex (MHC) class I gene expression in FRTL-5 thyrocytes. Iodide deficiency, also present in these patients, was separately suggested to enhance thyroidal MHC class I and class II gene expression in vivo and in vitro. To test the clinical relevance of these observations, we examined 41 nontoxic goiters surgically removed from patients who had compression problems. Northern analysis revealed that there was a mean 3.9-fold increase in MHC class I expression and a 8.3-fold increase in class II expression by comparison to 9 normal glands. In situ hybridization showed that thyrocytes were the main source of class I and class II transcripts; histological examination revealed that lymphocytic infiltration was minimal to nonexistent. The iodine content of the 41 nontoxic goiters was significantly lower than in normal glands, consistent with increased MHC class I and class II. There is also a profound accumulation of TG in the follicles of the nontoxic goiters, and TG purified from the follicles of these glands increased MHC class I gene expression in FRTL-5 thyroid cells significantly more than TG from normal glands per mg protein. Nearly all patients with nontoxic goiter had low, but significantly elevated, levels of antibodies against thyroid peroxidase and/or against TG in their sera compared with those in normal individuals. Moreover, there was a positive correlation between the titer of the serum antibodies against thyroid peroxidase and against TG and MHC class I and class II expression in the thyroid. The data support the possibility that the TG accumulated in the follicular lumen of nontoxic goiters together with relative iodine deficiency contributes to increased MHC expression in thyroid cells in vivo and that increased MHC gene expression contributes to the ability of thyroid antigens to trigger an autoimmune reaction.