Delayed Hypersensitivity in Graves' Disease and Exophthalmos: Identification of Thyroglobulin in Normal Human Orbital Muscle

Abstract

Patients with Graves'' disease and exophthalmos demonstrate delayed hypersensitivity to antigens present in extracts of certain normal human tissue; namely, thyroid gland and retroorbital tissue. The delayed hypersensitivity can be assayed in vitro by quantitating the amount of a lymphokine, migration inhibition factor (MIF), which is produced when T [thymus derived] lymphocytes of patients with Graves'' disease and exophthalmos are exposed to these antigens. A partial purification is described for the retro-orbital tissue antigen which is responsible for the positive leukocyte migration inhibition factor assay (MIF assay) exhibited by the sensitized lymphocytes of these patients. The purified retro-orbital tissue antigen preparation demonstrates a 50 to 150-fold higher specific activity over crude homogenates in its ability to act as an antigen in the MIF assay of exophthalmic patients. Immunodiffusion, ultracentrifugation and disc electrophoretic data indicate that this purified antigen preparation, obtained from normal human retro-orbital tissue, contains thyroglobulin [TG] or a derivative of TG, immunofluorescence studies localize the anti-TG reactive material to the plasma membranes of extraocular muscle fibers of normal individuals. TG or a derivative of the TG molecule is present in the orbital muscle of normal individuals. Since TG purified from normal human thyroid glands and the purified retro-orbital tissue preparation are nearly equivalent as antigens in the MIF assay of exophthalmic patients, it is concluded that TG or an antigenic component of the TG molecule is 1 of the antigens to which patients with Graves'' disease and exophthalmos demonstrate delayed hypersensitivity.