Immunological and Clinical Analysis of Experimental Heat Shock Protein-Induced Uveitis

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We have already demonstrated that the heat shock protein (HSP) T cell peptide determinants which specifically stimulate T cells from patients with ocular type Behcet's disease (BD) are capable of both inducing uveitis and stimulating lymphocyte proliferation in rats. In the present study, mycobacterial HSF 65 kD and those peptides were injected into Lewis rats, and IgG and IgA antibodies (Abs) were measured using an enzyme-linked immunosorbent assay (ELISA). Serum collected 21 days after immunization of HSP peptides from rats that developed uveitis showed significantly higher IgG Ab levels to peptide 311-326 and 336-351 than did serum samples collected from rats without uveitis. Significant elevation of levels of IgA Abs in rats that developed uveitis was also observed in rats immunized with 111-125, 311-326 and 336-351. 1. In rats injected with HSP 65 kD, the IgG Ab levels to peptide 111-125, 154-172 and 311-326 showed a considerable increase and the IgA Ab level to peptide 311-326 also showed a marked elevation. Marked inhibition of IgG Ab binding to HSP 65 kD by peptides 111-125, 154-172, 311-326 and 336-351 and of IgA Ab binding by peptides 311-326 and 336-351 were observed in rats immunized with HSP 65 kD. These results suggest that the epitopes responsible for ocular disease development and antibody production in rats injected with HSP 65 kD might be similar or identical to those that are most immunogenic for T cells from patients with ocular type BD, and that IgA Abs play a similar or more critical and important role compared with IgG Abs in the development and progression of HSP-induced uveitis, and that they can be used as markers of disease activity.