Antibodies to a microbial peptide sharing sequence homology with βA₃-crystallin damage lens epithelial cells in vitro and in vivo

Circulating auto-antibodies (Abs) against lens antigens (Ags) are highly prevalent in patients with cataract, but their origin and pathogenic significance are unknown. We hypothesized that Abs raised after exposure to infectious microbes could cross-react with lens Ags. To test this hypothesis, we generated a monoclonal Ab to human βA₃-crystallin. Epitope analysis indicated that the ETQAE sequence in the N-terminus region of βA₃-crystallin was critical for mounting a humoral response. Similar sequences were found in three microbial Ags. Mice injected with a microbial oligopeptide containing ETQAE emulsified with complete Freund's adjuvant (CFA) raised Abs which cross-reacted with βA₃-crystallin and developed lens epithelial cell (LEG) damage in vitro. We also genetically engineered an βA₃-crystallin-expressing E. coli. Mice immunized with the recombinant E. coli developed LEC damage. These results support the hypothesis that exposure to microbes having Ags homologous to self Ags can trigger a humoral immune response that leads to LEC damage in mice.