Although the mechanism of hyperthyroidism in Graves’ disease is well understood, the autoimmune process that causes it is not. Autoimmunity occurs when the immune system loses tolerance to “self” molecules and instead interprets them as harmful invaders and targets the tissues where they’re present. The mechanisms that break self-tolerance in Graves’ disease are not clear. Similar to other autoimmune diseases, loss of tolerance to “self” is likely due to a combination of genetic and environmental factors. It has been proposed that the thyroid proteins targeted by the immune system in people with Graves’ disease may have properties that contribute to loss of immune tolerance.[1] However, direct evidence for this hypothesis is lacking. Although several animal models are known to develop autoimmunity against the thyroid gland,[2] they differ from Graves’ disease in that these models are associated with different antibodies and do not develop hyperthyroidism.[1]
Loss of self-tolerance may also occur via common mechanisms across different autoimmune diseases because up to 25% of people with one autoimmune disorder tend to develop additional ones.[3] This phenomenon has also been observed for Graves’ disease, in which 20% of patients also have at least one additional autoimmune disorder.[4]
References
- ^McLachlan SM, Rapoport BBreaking tolerance to thyroid antigens: changing concepts in thyroid autoimmunity.Endocr Rev.(2014-Feb)
- ^David JM, Dick EJ, Hubbard GBSpontaneous pathology of the common marmoset (Callithrix jacchus) and tamarins (Saguinus oedipus, Saguinus mystax).J Med Primatol.(2009-Oct)
- ^Cojocaru M, Cojocaru IM, Silosi IMultiple autoimmune syndrome.Maedica (Bucur).(2010-Apr)
- ^Ferrari SM, Fallahi P, Ruffilli I, Elia G, Ragusa F, Benvenga S, Antonelli AThe association of other autoimmune diseases in patients with Graves' disease (with or without ophthalmopathy): Review of the literature and report of a large series.Autoimmun Rev.(2019-Mar)