In Graves disease, thyroid-stimulating autoantibodies activate the thyrotropin receptor (TSHR), leading to increased thyroid hormone secretion and clinical thyrotoxicosis, but the exact molecular interactions are not know. In 15 July Journal of Clinical Investigation, Gregorio D. Chazenbalk and colleagues show that the thyroid-stimulating autoantibodies preferentially recognize the free A subunit, not the thyrotropin holoreceptor (J Clin Invest 2002, 110:209-217).

Chazenbalk et al. studied sera from 20 patients with Graves disease using flow cytometry. They observed that epitopes recognized by a mouse thyroid-stimulating monoclonal antibody are poorly accessible when the thyrotropin holoreceptor is present on the cell surface. But despite poor recognition by thyroid-stimulating autoantibodies (TSAb's) of the holoreceptor, soluble TSHR A subunits (known to be shed from surface TSHR) fully neutralized autoantibody-binding activity.

These results "provide evidence that TSAb's in Graves disease preferentially recognize the free A subunit and not the TSH holoreceptor," concluded the authors. "This...