6910 Hypothyroidism Induced by a TSH Receptor Peptide -Implications for Thyroid Autoimmunity

Abstract Disclosure: P. xiang: None. R. Latif: None. S.A. Morshed: None. T.F. Davies: None. The “Neutral” thyrotropin receptor autoantibodies (N-TSHR-Ab) directed at the TSHR ectodomain's hinge region have been shown to induce thyroid cell damage in vitro and also when administered in vivo. For example, during these earlier studies we developed a mouse monoclonal antibody (MC1) specific for a peptide (aa 322-340) in the hinge region (MC1 - Mab) which was able to induce thyroid cell stress and apoptosis. In order to examine the effect of in vivo generated N-TSHR-Abs we immunized Balb/c mice with the same hinge region peptide and examined their thyroid function over the subsequent 18 weeks. We found that TSHR-peptide immunized mice developed N-TSHR-Abs against the peptide which resulted in thyroid damage shown by thyroid follicular cell apoptosis, thyroglobulin release, induction of thyroglobulin antibodies and hypothyroidism with increased TSH levels. These data add further evidence to the complexity of the immune response to the TSHR and indicate that the simple presence of stimulating type TSHR antibodies is not the entire story of Graves’ disease. Presentation: 6/3/2024