Type IIB Hypersensitivity: Graves’ Disease - Mechanisms of Autoimmune Tissue Injury and Examples

Type IIB Hypersensitivity: Graves’ Disease

Graves’ disease is an organ-specific auto-immune disease of the thyroid mediated by stimulatory (agonistic) autoantibodies. Autoantibodies to the thyroid-stimu-lating hormone receptor (TSHR) cause hyperthyroidism in patients with Graves’ disease. The pathogenicity of anti-TSHR autoantibodies is demonstrated by the occurrence of neonatal Graves’ disease after passive transplacental transfer of IgG thyroid-stimulating autoantibodies from a mother with Graves’ disease to the fetus. The anti-TSHR autoantibodies in Graves’ disease inhibit binding of TSH to its recep-tor 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 nevertheless stimulate TSHR signaling, causing increased production of thyroid hormone.