Abstract
Abstract: :
Purpose: For many autoimmune diseases, molecular mimicry of peptides from pathogens and autoantigens is believed to play a major role in disease induction. We have discussed antigenic mimicry of peptides derived from retinal S-Antigen (PDSAg) and disease associated HLA-antigens (B27PD) as a possible pathomechanism for autoimmune uveitis in man, however, a specific pathogen-derived antigen peptide is still missing. Data base search revealed amino acid homologies of retinal peptide PDSAg and 11mer peptides from Rotavirus (Rota) and Rickettsia (Rick) and of peptide B27PD and Propionibacter (Prop). We investigated uveitogenicity of these peptides in Lewis rats as well as immune responses of uveitis patients and healthy individuals to reveal a possible correlation of uveitis and infections with these pathogens. Methods: Lewis rats were immunized with peptides Rota, Rick and Prop and uveitis was determined clinically and histologically. Sera from 98 uveitis patients and 36 healthy individuals were tested in ELISA for reactivity with the respective peptides and tetanus toxoid. Results: Immunization of Lewis rats with Rotavirus peptide Rota induced uveits in 75% of Lewis rats. The disease was milder than that induced with peptide PDSAg and had a delayed onset of one week. Histologically the disease was similar to PDSAg-induced uveitis. Peptides Rick and Prop were not uveitogenic in Lewis rats. In sera from uveitis patients reactivity to peptides PDSAg, Rota and Rick was significantly higher (p<0.04 for PDSAg and p<0.0001 for Rota and Rick) than in sera from healthy individuals, wheras responses to Prop and tetanus toxoid were similar. Conclusion: Molecular mimicry of antigens from Rotavirus or Rickettsia might trigger autoreactivity resulting in uveitis. Rotavirus could be a candidate of special interest, due to its high endemic infection rate and the uveitogenic potential of the outer capsid derived peptide Rota in rats.
Keywords: 327 autoimmune disease • 612 uveitis-clinical/animal model