The thyrotropin receptor (TSHR) represents the central autoantigen involved in GD and has been proposed as the thyroid antigen shared with the orbit that could explain the infiltration of immune cells into tissues surrounding the eye.
GD is a systemic autoimmune thyroid disorder characterized by the infiltration of immune effector cells and thyroid-antigen-specific T cells into the thyroid and thyroid stimulating hormone receptor (TSHR) expressing tissues, i.e. orbit, skin, with the production of autoantibodies to well-defined thyroidal antigens.
Recent studies have suggested a link between the stimulation of adipogenesis within the orbit in GO and the expression in these tissues of TSH receptor (TSHR), the putative orbital autoantigen.
As the TSH receptor (TSHR) is the primary target for autoimmunity against the thyroid in Graves' disease, much effort has gone into investigating the role of TSHR messenger ribonucleic acid (mRNA) transcripts in extrathyroidal tissue, particularly in the orbit.
Recent evidence suggests that TSHR may also serve as an orbital autoantigen in Graves' ophthalmopathy (GO) and that expression of this protein is increased in the fatty connective tissues of the orbit in this condition.
Our results suggest that TNF-alpha, IFN-gamma, and transforming growth factor-beta may act within the orbit in GO to modulate expression of the putative orbital autoantigen, TSHr.
These studies suggest that the expression of this receptor in the orbit in vivo may be stimulated by TSH or other TSHr ligands, and that this stimulation may be important in the development of GO.
These results suggest that the expression of TSH-R in the orbit, especially fibroblasts, may play a role in the pathogenesis and clinical manifestations of the ophthalmopathy in patients with TAO, although a secondary effect, involving fibroblasts in TAO is also possible.
Although the presence of this TSH-R variant could provide the antigenic link between the thyroid and the orbit in Graves' disease and thyroid-associated ophthalmopathy (TAO), the etiopathophysiological significance of this finding remains to be elucidated.