Epitope hunting in rheumatoid arthritis : towards antigen specific immunotherapy

Abstract

Current treatment options in rheumatoid arthritis aim to dampen the immune response a-specifically. In the last decennia new strategies have emerged that have fewer side effects due to more specificity by focussing on those cells of the immune system that deal with regulation. Epitope specific immunotherapy is, among other therapies, a realistic choice for the future. In this thesis we present the identification of new heat shock protein 60 epitopes, new proteoglycan aggrecan epitopes and new heat shock protein 70 T cell epitopes in rheumatoid arthritis and healthy controles. In order to identify these epitopes we used different hunting strategies. We found recognition of the epitopes by peripheral blood mononuclear cells and synovial fluid derived mononuclear cells. Interestingly the phenotype of the immune response induced was different, depending upon the epitope admitted. For instance proteoglycan epitopes induced a pathogenic immune response in vitro, while heat shock protein 60 epitopes induced a tolerogenic response, by the induction of regulatory T cells. We also showed that this approach is not always successful. In Sjogrens's syndrome patients for example we were unable to detect a heat shock protein 60 epitope specific response. In conclusion, In this thesis we have partly paved the route towards antigen specific immunotherapy in rheumatoid arthritis. The identified epitopes could be the new targets for such epotope specific immunotherapy.