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, respectively. Despite their opposing clinical manifestation, they have several enigmatic 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 nodules. These T cells can trigger a humoral response in susceptible individuals, leading 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.