Thyroid peroxidase

Thyroid peroxidase, also known as thyroperoxidase (TPO), is a 100 kDa, glycosylated heme-protein bound to the apical membrane of the thyrocyte. The TPO gene has been mapped at 2p13. It comprises 17 exons, spanning more than 150 kb of DNA. Inactivating mutations of the TPO gene result in partially or totally deficient iodide organification and, consequently, in hypothyroidism. TPO is synthetized in polyribosomes and undergoes glycosylation in the Golgi apparatus. Upon packaging into vesicles, TPO reaches the apical membrane. TSH stimulates all these steps, from TPO production to targeting to the apical membrane of the thyrocyte. TPO, thyroglobulin (Tg) and TSH receptor are the major thyroid autoantigens. TPO has been isolated and identified only in the 80s as the “thyroid microsomal antigen,” previously reported as a target of the autoimmune process in Hashimoto’s thyroiditis. Similarly to Tg autoantibodies (Ab), TPOAb are found also in patients with Graves’ disease, underlining that both Hashimoto’s thyroiditis and Graves’ disease are characterized in their initial stage by a common breakdown of self-tolerance. Up to 10% of euthyroid subjects can be found positive for TPOAb and are at risk of developing an autoimmune thyroid disease (AITD), as demonstrated by precociously altered ultrasound echogenicity. Moreover, a number of studies have highlighted the relation between thyroid autoimmunity and cancer.