Epitopes specificity of antibodies to thyroid peroxidase in patients with Graves’ disease, Hashimoto’s thyroiditis and overlap-syndrome

BACKGROUND: Antibodies against thyroid peroxidase (anti-TPO) serve as clinical markers of thyroid autoimmune diseases (TAIDs). By trying to elucidate the causes of heterogeneity in autoantibody levels among patients with different TAIDs it becomes possible to clarify the pathophysiology of GD and HT. OBJECTIVE: To investigate the heterogeneity of epitopes recognized by anti-TPO in patients with Hashimoto’s thyroiditis (HT), Graves’ disease (GD) and overlap-syndrome. METHODS: We carried out a cross-sectional study on 398 patients with GD, HT and overlap syndrome and analyzed the specificity of epitopes and binding constants of TPO with monoclonal antibodies (MAbs). Ten MAbs to TPO were used, of which five were reactive with native TPO and the rest were reactive with denaturated TPO. RESULTS: The autoantibodies in blood serum of HT patients inhibited the binding of MAb63 more significantly than those in serum of GD patients: 59.62 % versus 54.02 %, respectively (p = 0.001). The anti-TPOs in serum of GD patients inhibited the binding of MAb77 more significantly than those in serum of HT patients: 54.36 % versus 51.13 %, respectively (p = 0.047). The binding of MAb45 was more inhibited in serum of patients with anti-TPO concentration over 1000 IU/ml (58.36 %). The blood serum of patients with overlap-syndrome showed less significant inhibition of MAb63 binding than that of patients with no overlap-syndrome: 52.47 % versus 58.81 %, respectively (p = 0.043). CONCLUSION: Mapping the epitopes to TPO with the help of MAbs may improve the differential diagnosis between different thyroid autoimmunities.