AUTOIMMUNE ENDOCRINE OPHTHALMOPATHY AND RETROBULBAR ANTIGENS

Endocrine Ophthalmopathy (EO) is based on autoimmune processes that le ad to lymphocyte infiltration of the retrobulbar space. In this study, antigenic character of retrobulbar adipose, connective and muscle tis sue as well as of cultured fibroblasts and myoblasts were examined. Sa mples were obtained from EO patients (n = 13, 8 fem., age 26-82 years, median 47 years) undergoing orbital decompression surgery. Retrobulba r and abdominal tissue from 7 controls (4 fem., 48-74y) was investigat ed, too. Tissues were homogenized and the proteins were separated by S DS-PAGE according to molecular weight. In order to recover the separat ed proteins in soluble form, an electroelution technique was employed. Twenty-two separated soluble protein fractions were used as antigenic stimuli for autologous peripheral blood mononuclear cells (PBMC) sepa rated by Ficoll gradient centrifugation. Subsequently, the proliferati on of T cells was measured by [H-3]-thymidine uptake. A marked T cell re sponse to protein fractions with molecular weight of 6-10 kD and 19 -26kD was detected (p<0.001). These autoantigens were found readily re producible in adipose tissue in 8 out of 9 EO patients, stimulation in dex (SI) to antigen 6 -10 kD 29 +/- 4.6 (mean+/-SEM); 19 -26 kD 5 +/- 1.4 and in 3 out of 4 patients using retrobulbar eye muscle tissue (SI : 6-10kD 23 +/- 4.2; 19-26 kD 6 +/- 2). Using the proteins of cultured fibroblasts as antigen, the autologous PBMC from 2 out of 4 tested EO -patients also responded;(SI: 7 +/- 2; 4 +/- 1.4). Testing cultured re trobulbar myoblasts of an EO patient, a response to the 19 -26 kD anti gen was found only (SI: 8.0). In response to retrobulbar adipose or mu scle proteins, PBMC of Z controls showed also a higher proliferation r ate (SI: 16 +/- 3.5; 13 +/- 2.8), whereas, a response to abdominal adi pose or muscle proteins (4 controls) was never found. Thus, two orbita l antigens reacting with autologous T cells could be demonstrated and may play an important role in the immunopathogenesis of EO. According to these findings, retrobulbar fibroblast antigens are most likely the main T cell targets.