Cellular and Humoral Immune Responses of Patients With Uveitis to Type I Collagen

Abstract

Abstract: : Purpose: We have reported that the target auto–antigen in EAAU, which serves as an animal model for idiopathic human anterior uveitis (AAU), is a 22 kDa fragment of bovine type I collagen–α2 chain– CI–α2 (22 kDa). This study was designed to evaluate and compare immune responses to CI–α2 (22 kDa) in the blood of uveitis patients and normal controls. Methods: The human response to bovine antigen was characterized by ELISA and a T cell proliferation assay. Three groups of patients with uveitis were included in this study, those with idiopathic AAU (n=10), chronic idiopathic panuveitis (n=10), and pars planitis (n=10). All the patients had clinically active disease. The patients were evaluated by history, clinical examination, and the diagnostic testing. Blood from ten healthy donors with no history of eye disease formed the control group. All human studies were performed following the guidelines of the declaration of Helsinki and were approved by the institutional review board. Results: The age in control and patient groups was comparable; average age 45 years (range, 20–65). Various disease entities responded differently to bovine CI–α2 (22 kDa). The patients with idiopathic AAU had a significantly elevated T cell proliferative response. The mean proliferative response to the purified antigen was as follows: AAU patients – 6.5 + 1.2, p<0.0l, chronic idiopathic pan uveitis 2.3 + 0.08, pars planitis – 1.8+ 0.02, and normal controls – 1.5+0.03. The sera from these patients were also tested for the presence of anti– CI–α2 (22 kDa) antibodies. All ten healthy controls gave an OD₄₁₀ < 0.1, as did the patients with chronic idiopathic pan uveitis and pars planitis (OD₄₁₀ < 0.1). In contrast, all ten patients with idiopathic AAU had detectable anti– CI–α2 (22 kDa) serum antibodies (OD₄₁₀ > 0.4). Conclusions: Our results suggest that the cellular and humoral responsiveness to purified bovine antigen was associated with idiopathic human AAU. Thus, idiopathic AAU may be the result of autoimmunity to a local ocular collagen confined to the anterior segment of the eye.

Keywords: autoimmune disease • uveitis-clinical/animal model • inflammation