Endocrine Abstracts

Objective: Graves’ disease (GD), also known as toxic diffuse goiter, is an autoimmune thyroid disorder caused by thyroid-stimulating autoantibodies (TSAb) against the thyrotropin receptor (TSHR), resulting in overstimulation of the thyroid gland and hyperthyroidism. Thyroid eye disease (TED) is a chronic inflammatory condition of the orbit and the most common extra thyroidal manifestation of Graves’ disease (GD) affecting approximately 40% of GD patients. A complex immune-mediated cycle involving lymphocytes, adipocytes, and orbital fibroblasts underlies TED. The aim of this study was to evaluate the therapeutic effect of maraviroc, a CCR5 receptor antagonist, in Graves’ disease and thyroid eye disease.

Methods: Mice were immunized with either a TSHR A-subunit plasmid for induction of Graves’ disease or a with ß-Gal plasmid as a control. Maraviroc was administered orally to one of the TSHR immunized groups for eight weeks. The typical clinical features of thyroid eye disease and inflammation were assessed by serological and immunohistochemical analysis.

Results: Maraviroc treatment mitigated autoimmune hyperthyroidism without affecting body weight. In the orbit, it normalized brown adipose tissue levels and showed a trend towards reduced T-cell infiltration, albeit not statistically significant. Maraviroc also reduced macrophage infiltration, particularly F4/80+ macrophages, in the TSHR-immunized group.

Conclusion and outlook: In this study, a mouse model of GD and TED was used to compare the therapeutic effect of Maraviroc between TSHR immunized and ß-Gal control mice. Our results show that maraviroc blocks the development of the local pathologies of GD and TED in the severe phase of the autoimmune disorder and slightly prevents development of the autoimmune response. Our findings suggest a beneficial effect of the drug on the outcome of experimental GO, but further studies are needed to better understand the molecular mechanisms of action of maraviroc and to develop therapies, especially for thyroid eye disease.