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Oral tolerance for treating uveitis - new hope for an old immunological mechanism
Stephan R Thurau1, Gerhild Wildner
1Department of Ophthalmology, Ludwig-Maximilians-University, Mathildenstr. 8, 80336, München, Germany.
Oral tolerance induction has evolved as an attractive approach for the treatment of autoimmune uveitis. This approach is effective and generally void of the side effects associated with conventional immunosuppression. Following uptake of soluble antigen via the gut mucosa a specific systemic tolerance is generated. Experimental autoimmune diseases such as uveitis can efficiently be treated when autoantigens are fed to animals. The immunological mechanisms of oral tolerance are not well understood but are thought to involve the recognition of tolerogenic epitopes, generation of suppressor T cells and altered regulation of selected cytokines. The dose, purity of the antigen (tissue extract vs. single peptide) and concomitant treatment with cytokines were evaluated with the aim to enhance oral tolerance. Immunomodulatory drugs can abrogate oral tolerance. This requires careful evaluation with respect to therapeutic approaches in patients. The first clinical trials for treatment of uveitis with oral retinal autoantigen or an HLA-peptide crossreactive with S-Antigen show a promising therapeutic effect and confirmed the safety of this approach.
Oral tolerance induction has evolved as an attractive approach for the treatment of autoimmune uveitis. This approach is effective and generally void of the side effects associated with conventional immunosuppression. Following uptake of soluble antigen via the gut mucosa a specific systemic tolerance is generated. Experimental autoimmune diseases such as uveitis can efficiently be treated when autoantigens are fed to animals. The immunological mechanisms of oral tolerance are not well understood but are thought to involve the recognition of tolerogenic epitopes, generation of suppressor T cells and altered regulation of selected cytokines. The dose, purity of the antigen (tissue extract vs. single peptide) and concomitant treatment with cytokines were evaluated with the aim to enhance oral tolerance. Immunomodulatory drugs can abrogate oral tolerance. This requires careful evaluation with respect to therapeutic approaches in patients. The first clinical trials for treatment of uveitis with oral retinal autoantigen or an HLA-peptide crossreactive with S-Antigen show a promising therapeutic effect and confirmed the safety of this approach.