Immune 4


Type IIB Hypersensitivity: Graves Disease

Graves disease is an organ-specific autoimmune disease of the thyroid mediated by stimulatory (agonistic) autoantibodies. Autoantibodies to the thyroid stimulating hormone receptor (TSHR) cause hyperthroidism in patients with Graves disease. The pathogenicity of anti-TSHR autoantibodies is demonstrated by the occurence of neonatal Graves disease after passive transplacental transfer of IgG thyroid stimulating autoantibodies in Graves disease inhibit binding of TSH to its receptor by binding to a conformational  epitope (the part of the antigen recognized by an antibody) of the extracellular domain of the TSHR. Although the autoantibodies appear to interact with TSHR somewhat differently than the natural ligand, they nevertheles stimulate TSHR signaling, causing increased production of thyroid hormone.

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