Immune Responses in Graves’ Orbitopathy (GOCART)

Research summary

Around a quarter of patients with the most common cause of thyroid gland overactivity (Graves' disease) develop a complication known as Graves' orbitopathy (GO). In GO, tissues in the space behind the eyeballs (the orbit) become inflamed, causing pressure to build up. This causes intense pain, restriction of eye movements, and in some cases permanent damage to sight. The pressure causes the eyeballs to bulge forward (proptosis), causing a startled, staring appearance which is disfiguring and a cause of great psychological harm (at least a third develop significant depression and anxiety). Following an initial highly active phase, patients with GO develop long lasting changes in the tissues of the orbit, which means the eyeballs remain projected forwards. Patients may be treated with high doses of steroids, and some require surgery to decompress the orbit, both to save sight and also to improve the appearance of the eyes. It is well established that antibodies targeting a receptor which stimulates the thyroid gland are the cause of its overactivity in Graves' disease. Whilst this antibody is also important in GO, the majority of GD patients do not develop this complication. Why this might be is unknown. We also don't know if different antibodies are important in GO, and whether they are made by inflammatory cells local to the eye. The reason some patients develop long term disfigurement is also not understood. In this project, we will use advanced techniques to analyse the makeup of the inflamed orbit, one cell at a time, from samples taken during decompression surgery. We will look at the antibody producing cells in the orbit and compare them to those in the blood, to see whether they are likely to be driving the disease. We will also look to see how the cells in the orbit are different between the initial and long term phases, and if there are subsets which may be responsible for this progression. Finally, we will perform experiments to see how antibodies and other inflammatory molecules cause changes in fibroblasts, important structural cells of the orbit.

Principal Investigator

Dr Alexander Clarke

Contact us

Email: ERGO@ouh.nhs.uk

IRAS number

303518