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G. Wildner, M. Diedrichs-Moehring; Induction of Uveitis by Breaking Oral Tolerance to a Nutrional Antigen . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4303.
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Purpose: Exogenous antigens such as infectious agents mimicking autoantigens are suspected triggers of autoimmune diseases by initiating defensive immune responses. Nutritional antigens are normally tolerated by the immune system. However, under certain conditions (e.g. concomitant infections) food antigens can be attacked by the immune system as well, leading to food allergies or even to autoimmune diseases. Here we demonstrate the induction of EAU by bovine milk casein, a common food antigen, which can mimic retinal S-Antigen peptide. Methods: Lewis rats were subcutanously immunized with retinal S-Ag-peptide (PDSAg), a peptide from bovine casein (Cas) or the whole casein protein, both emulsified in CFA, to induce uveitis. Rat T cell lines specific for these antigens were analyzed in vitro for crossreactivity and in vivo for pathogenicity (adoptive transfer). We furthermore tested the ability of casein and Cas to elicit oral tolerance to PDSAg-induced uveitis. To prove the concept of breaking oral tolerance as an initiating event of the autoimmune response we cofed rats with casein, S-Ag, as well as the respective peptides and Cholera toxin. We furthermore tested sera and peripheral blood lymphocytes from uveitis patients and healthy donors for casein-specific responses. Results: Immunization with casein peptide and casein protein induced uveitis in up to 75% of rats. Casein and Cas specific T cell lines were crossreactive with S-Antigen peptide and uveitogenic after adoptive transfer in 25-65% of rats. Peptide Cas was orally tolerogenic, whereas casein failed to prevent PDSAg-induced uveitis.Interestingly, following concomitant feeding of casein (but not Cas and PDSAg) with Cholera toxin 75% of rats developed uveitis. Patients with iritis had significantly elevated antibody (p<0.05) and T cell responses to casein, Cas and S-Ag compared to healthy donors. Conclusions: Breaking oral tolerance to bovine casein, a common food antigen in industrialized countries, might initiate an immune response that crossreacts with retinal S-Antigen and thus lead to autoimmune uveitis.
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