Autoimmune thyroid diseases as a cost of physiological autoimmune surveillance

Graves' disease (GD) and Hashimoto's thyroiditis (HT) are common autoimmune diseases of the thyroid gland, causing hyperthyroidism and hypothyroidism, re-spectively. Despite their opposing clinical manifestation, they have several enig-matic links. Here, we propose that GD and HT have the same fundamental origin: both diseases are the cost of a beneficial physiological process called autoimmune surveillance of hypersecreting mutants. Autoreactive T cells selectively eliminate mutant cells that hypersecrete the hormones and threaten to become toxic nod-ules. These T cells can trigger a humoral response in susceptible individuals, lead-ing to the production of antibodies against thyroid antigens. This shared origin can explain similarities in incidence and risk factors between HT and GD, despite their opposite clinical phenotypes.