Effects of Thyrotropin and Thyrotropin-Receptor-Stimulating Graves' Disease Immunoglobulin G on Cyclic Adenosine Monophosphate and Hyaluronan Production in Nondifferentiated Orbital Fibroblasts of Graves' Ophthalmopathy Patients

Thyroid ◽  
2010 ◽  
Vol 20 (5) ◽  
pp. 535-544 ◽  
Author(s):  
Clementine J.J. van Zeijl ◽  
Eric Fliers ◽  
Chris J. van Koppen ◽  
Olga V. Surovtseva ◽  
Marcel E. de Gooyer ◽  
...  
Keyword(s):  
Immunoglobulin G ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Graves Disease ◽  
Thyrotropin Receptor ◽  
Graves Ophthalmopathy ◽  
Orbital Fibroblasts

scholarly journals 40 YEARS OF IGF1: IGF1 receptor and thyroid-associated ophthalmopathy

2018 ◽  
Vol 61 (1) ◽  
pp. T29-T43 ◽  
Author(s):  
Michelle Mohyi ◽  
Terry J Smith
Keyword(s):  
Graves Disease ◽  
Physical Interaction ◽  
Therapeutic Trial ◽  
Thyrotropin Receptor ◽  
Autoimmune Process ◽  
The Past ◽  
Thyroid Associated Ophthalmopathy ◽  
Upper Face ◽  
Igf1 Receptor ◽  
Orbital Fibroblasts

Thyroid-associated ophthalmopathy (TAO) is a vexing and poorly understood autoimmune process involving the upper face and tissues surrounding the eyes. In TAO, the orbit can become inflamed and undergo substantial remodeling that is disfiguring and can lead to loss of vision. There are currently no approved medical therapies for TAO, the consequence of its uncertain pathogenic nature. It usually presents as a component of the syndrome known as Graves’ disease where loss of immune tolerance to the thyrotropin receptor (TSHR) results in the generation of activating antibodies against that protein and hyperthyroidism. The role for TSHR and these antibodies in the development of TAO is considerably less well established. We have reported over the past 2 decades evidence that the insulin-like growth factorI receptor (IGF1R) may also participate in the pathogenesis of TAO. Activating antibodies against IGF1R have been detected in patients with GD. The actions of these antibodies initiate signaling in orbital fibroblasts from patients with the disease. Further, we have identified a functional and physical interaction between TSHR and IGF1R. Importantly, it appears that signaling initiated from either receptor can be attenuated by inhibiting the activity of IGF1R. These findings underpin the rationale for therapeutically targeting IGF1R in active TAO. A recently completed therapeutic trial of teprotumumab, a human IGF1R inhibiting antibody, in patients with moderate to severe, active TAO, indicates the potential effectiveness and safety of the drug. It is possible that other autoimmune diseases might also benefit from this treatment strategy.

scholarly journals The Role of Oxidative Stress on the Pathogenesis of Graves' Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Miloš Žarković
Keyword(s):  
Oxidative Stress ◽  
The Other ◽  
Graves Disease ◽  
Graves Ophthalmopathy ◽  
Selenium Treatment ◽  
Graves Orbitopathy ◽  
Eye Involvement ◽  
Orbital Fibroblasts

Graves' disease is a most common cause of hyperthyroidism. It is an autoimmune disease, and autoimmune process induces an inflammatory reaction, and reactive oxygen species (ROSs) are among its products. When balance between oxidants and antioxidants is disturbed, in favour of the oxidants it is termed “oxidative stress” (OS). Increased OS characterizes Graves' disease. It seems that the level of OS is increased in subjects with Graves' ophthalmopathy compared to the other subjects with Graves' disease. Among the other factors, OS is involved in proliferation of orbital fibroblasts. Polymorphism of the 8-oxoG DNA N-glycosylase 1 (hOGG1) involved in repair of the oxidative damaged DNA increases in the risk for developing Grave's disease. Treatment with glucocorticoids reduces levels of OS markers. A recent large clinical trial evaluated effect of selenium on mild Graves' ophthalmopathy. Selenium treatment was associated with an improved quality of life and less eye involvement and slowed the progression of Graves' orbitopathy, compared to placebo.

Sign in / Sign up

Export Citation Format

Share Document