Human S-antigen determinant recognition in uveitis.

PURPOSE Soluble antigen (S-Ag) is a member of the arrestin family of protein with which it shares a high level of homology. It is an immunologically privileged retinal antigen that can elicit experimental autoimmune uveitis (EAU) and is thought to be a target for ocular inflammatory diseases. This study was conducted to identify in humans, the immunogenic determinants of human S-Ag and to establish whether a specific response profile occurs in particular ocular inflammatory conditions. METHODS Peripheral blood lymphocyte responses were measured against a panel of 40 overlapping synthetic peptides of human S-Ag in patients with chronic uveitis and compared with control subjects. Patients with Behçet disease, sarcoidosis, Vogt-Koyanagi-Harada, and sympathetic ophthalmia were tested. RESULTS A limited number of immunodominant determinants were identified for Behçet disease and sarcoidosis. These were all located at sites of limited homology with other known arrestins. In addition, several individual patients had prominent proliferative responses to multiple determinants well above that of control subjects. This determinant spread was observed in all disease entities except sympathetic ophthalmia, which did not show any immunoreactivity to S-Ag. Significant response shifts were also noted over time in two patients. CONCLUSIONS The results indicate that there are specific immunodominant determinants to human S-Ag in patients with certain forms of uveitis. However, in individual patients, response is not limited to these determinants. In the chronic stage of disease, response is spread over many determinants.