FAILURE TO DEMONSTRATE CELL-MEDIATED-IMMUNITY TO ORBITAL TISSUE ANTIGENS AND EPITOPIC FRAGMENTS OF A 64-KDA PROTEIN IN THE MAJORITY OF PATIENTS WITH THYROID-ASSOCIATED OPHTHALMOPATHY

We have studied a possible role of T cell sensitization to eye muscle antigens in patients with thyroid-associated ophthalmopathy (TAO). Per ipheral blood mononuclear cell (PBMC) proliferation in response to cru de porcine orbital tissue antigens, partially purified porcine eye mus cle membrane proteins and predicted epitopic fragments of the recombin ant 64 kDa protein 1 D, was determined in patients with TAO and thyroi d autoimmunity without eye disease, When membrane and cytosol fraction s were used as antigen PBMC from 43% of patients with TAO but only 12. 5% of normal subjects were responsive to a crude orbital connective ti ssue membrane fraction, although this difference was not significant. We were unable to demonstrate specific recognition of partially purifi ed eye muscle membrane fractions; although most of the fractions teste d were occasionally recognized by T cells from patients with ophthalmo pathy, this was also the case for patients with autoimmune thyroid dis ease without ophthalmopathy and normal subjects. We did not clearly id entify epitopic sequences within the 1D protein, most of the predicted peptides tested being recognized not only by T cells from a small pro portion of patients with TAO, but also by those from some patients wit h autoimmune thyroid disease without ophthalmopathy and normal subject s. It is noteworthy however that approximately 22% of TAO patients, bu t no normal subjects, were positive to one or more of three peptides, suggesting that reactivity to the 1D protein may play a role in the pa thogenesis of the eye disorder in some patients with TAO. The inconsis tent and generally low T cell responses to crude and purified antigens noted in a few patients with TAO could be explained by low numbers of specifically sensitized lymphocytes in peripheral blood.