The nature of the putative autoantigen in Graves' ophthalmopathy (Go) remains an enigma but the sequence similarity between thyroglobulin (Tg) and acetylcholinesterase (ACHE) provides a rationale for epitopes which are common to the thyroid gland and the eye orbit.
The nature of the putative autoantigen in Graves' ophthalmopathy (Go) remains an enigma but the sequence similarity between thyroglobulin (Tg) and acetylcholinesterase (ACHE) provides a rationale for epitopes which are common to the thyroid gland and the eye orbit.
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.
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.
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.
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.
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.
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.
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.
These findings suggest that IL-6 may play a role in the pathogenesis of GO by increasing expression of the putative autoantigen within the adipose/connective tissues of the orbit.
Whether IL-6 also stimulates adipogenesis in the orbit is unclear at present, but such an effect could contribute to the increased volume of orbital adipose/connective tissue characteristic of this condition.
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.
Magnetic Resonance Imaging (MRI) of the orbit, in one family, showed absence or hypotrophy of the eyelid superior levator muscle suggesting a possible role of FOXL2 in the development of this extra-ocular muscle.
The increased expression of the macrophage-derived cytokines IL-1 beta, TNF-alpha, and IL-10 suggests the presence of macrophage activation and ongoing antigen presentation within the orbit in GO.
The increased expression of the macrophage-derived cytokines IL-1 beta, TNF-alpha, and IL-10 suggests the presence of macrophage activation and ongoing antigen presentation within the orbit in GO.
In addition to these direct effects, cytokines can modulate the immune reaction in GO by increasing major histocompatibility complex (MHC) class II, adhesion molecules, CD40, prostaglandin and heat shock protein expression in the orbit, thereby having a role in localising and augmenting the inflammatory response.
Orbital imaging in CFEOM1 due to various amino acid substitutions in the kinesin KIF21A demonstrates consistent abnormalities of motor and sensory innervation in the orbit.
These results support the concept that orbital adipogenesis is enhanced in GO and suggest that elevated levels of sFRP-1 in the GO orbit may be involved in stimulating this pathogenic process.
Thus, the exaggerated capacity of orbital fibroblasts to express high levels of both IL-6 and its receptor in an anatomic site-selective manner could represent an important basis for immune responses localized to the orbit in Graves' disease.