Graves’ disease is an autoimmune disorder characterised by pathogenic thyroid stimulating receptor (TSHR) antibodies. With a global prevalence of 0.5-2% and an annual incidence of 1 in 4000/year, it has significant physiological, emotional and financial burden [1,2]. Current treatment options do not target the underlying immune mechanism and are suboptimal with issues of inadequate remission, side effects and chronic pill burden . Previous studies have examined T cell responses to autoantigens in the peripheral blood of Graves’ disease patients, but results have been inconclusive as to the most immunogenic self-peptides[4-6]. To better understand the local autoimmune response, this study aims to identify the most immunogenic TSH receptor epitopes from thyroid tissue itself.
Human thyroid tissue was obtained from three Graves’ disease patients undergoing elective thyroidectomy. In a novel technique, CD4+ T cells were isolated, expanded and cloned from thyroid tissue over 3-4 weeks. Reactivity of each clone towards 31 overlapping peptides of the TSHR extracellular domain was tested in the presence of matched antigen presenting cells using IFN-g ELISA.
Preliminary results in a HLA-DR DRB1*1301+ 1501+ patient with treatment-resistant Graves’ disease shows that individual clones produce IFN-g in response to several TSHR peptide groups. Reactivity of identified epitopes will be confirmed in this patient’s peripheral blood mononuclear cells, and peptide reactivity of clones derived from the other 2 patients will be tested. This study will provide important information regarding the thyroid-specific T cell immune responses in Graves’ disease. Through delineation of the immunogenic peptides, we will develop a precise understanding of the immunogenic region of the TSHR autoantigen in Graves’ disease. This will provide a foundation for further research into new diagnostic tests and treatment options.