Autoantibodies to the thyroid microsomal/thyroid peroxidase antigen are polyclonal and directed to several distinct antigenic sites.

A detailed examination of the epitopes recognized by autoantibodies (aAbs) to the thyroid microsomal antigen/thyroid peroxidase (TMA/TPO) in patients with thyroid autoimmune disease has been made using a combination of immunochemical and enzymatic techniques. Our results demonstrate the the autoimmune response to thyroid microsomal antigen/thyroid peroxidase (TMA/TPO) is multifocal and far more heterogeneous than hitherto recognized. By immunoblotting with aAbs, antigenic determinants on the TMA/TPO have been recognized that are either susceptible to polypeptide denaturation and/or sensitive to the effects of reducing agents. Furthermore, these aAbs can inhibit, to varying degrees, the enzymatic activity of solubilized preparations of TPO in microsomes, as ascertained by peroxidation of guaiacol and iodide. A large proportion of the autoimmune response is directed to the guaiacol peroxidation site. The data support the view that the autoimmune reactivity to the TMA/TPO is a specific polyclonal response with a minimum of six distinct, independent determinants that are recognized by aAbs.