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

Recent studies suggest that thyroglobulin (TG) accumulated in the follicula r lumen of colloid nodular goiters can increase major histocompatibility co mplex (MHC) class I gene expression in FRTL-5 thyrocytes. Iodide deficiency , also present in these patients, was separately suggested to enhance thyro idal MHC class I and class LI gene expression in vivo and in vitro. To test the clinical relevance of these observations, we examined 41 nontoxic goit ers surgically removed from patients who had compression problems. Northern analysis revealed that there was a mean 3.9-fold increase in MHC class I e xpression 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 reveal ed that lymphocytic infiltration was minimal to nonexistent. The iodine con tent of the 41 nontoxic goiters was significantly lower than in normal glan ds, consistent with increased MHC class I and class II. There is also a pro found accumulation of TG in the follicles of the nontoxic goiters, and TG p urified from the follicles of these glands increased MHC class I gene expre ssion in FRTL-5 thyroid cells significantly more than TG from normal glands per mg protein. Nearly all patients with nontoxic goiter had low, but sign ificantly elevated, levels of antibodies against thyroid peroxidase and/or against TG in their sera compared with those in normal individuals. Moreove r, there was a positive correlation between the titer of the serum antibodi es against thyroid peroxidase and against TG and MHC class I and class II e xpression in the thyroid. The data support the possibility that the TG accu mulated 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 o f thyroid antigens to trigger an autoimmune reaction.