Graves Disease Induced by Shed Antigens

Researchers have found that the autoantibodies against the thyroid gland that cause the hyperthyroidism characteristic of Graves disease preferentially recognize an antigen that is cleaved from the thyroid stimulating hormone receptor (TSHR) and shed into the extracellular milieu.

Investigators at Cedars-Sinai Medical Center (Los Angeles, CA, USA) used a novel adenovirus-mediated animal model of Graves disease to show that goiter and hyperthyroidism occur to a much greater extent when the adenovirus expressed the free A subunit as opposed to a genetically modified TSHR that did not readily cleave into subunits. Non-cleaving glycoprotein hormone receptors did not generate functional autoantibodies. These findings were published in the June 16, 2003, issue of the Journal of Clinical Investigation.

The authors conclude, "These data show that shed A subunits induce or amplify the immune response leading to hyperthyroidism and provide a new insight into the etiology of Graves disease.” They also note, however, that while the data increase help to explain why autoantibodies arise to the TSHR, stimulate the thyroid, and result in Graves hperthyroidism, the mechanisms responsible for TSHR cleavage require further exploration.




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