Infectious and non infectious triggers in non‐infectious uveitis

Purpose The induction of autoimmune uveitis is difficult to explain with respect to the immune privileged status of the eye. The intact BRB can only be passed by already activated leukocytes, which should normally be ignorant to the sequestered intraocular antigens. Antigenic mimicry of retinal autoantigens by environmental proteins could explain extraocular activation of effector T cells. Methods We have previously demonstrated antigenic mimicry of a peptide from retinal S‐Antigen and peptides from rotavirus (Rota) and bovine milk casein (Cas). Both, Rota and Cas, induce T cell lines cross‐reactive with retinal S‐Ag peptide as well as experimental autoimmune uveitis in rats. Patients with uveitis have increased antibody and T cell responses to the mimicry peptides as well as to the S‐Ag peptide compared to healthy donors. Accordingly, Infection with rotavirus or any gastrointestinal pathogen with concomitant ingestion of bovine milk products could induce an immune response in the gastrointestinal tract that is cross‐reactive with ocular autoantigens and lead to induction of autoimmunity in the eye. Results Uveitis as a well known adverse effect after BCG (Bacille Calmette Guerin) treatment might also be the result of antigenic mimicry. We have shown T cell responses to PPD from M. tuberculosis and the retinal autoantigens S‐Ag, IRBP and CRALBP from a patient who had developed granulomatous uveitis after BCG application for bladder carcinoma. Data base searches revealed a number of amino acid sequence homologies between proteins from mycobacteria and retinal autoantigens, suggesting antigenic mimicry. These findings might as well be an explanation for the occurrence of uveitis in connection with M. tuberculosis infection, even when no mycobacteria are detectable in the eye.