Coeliac disease (CD) and rheumatoid arthritis (RA); mapping the shared features in order to understand autoimmunity

There has been a huge advance in the understanding of coeliac disease (CD) in recent years. Our group has made several important contributions to this improved understanding. Research done by other groups has started to unravel aspects of the pathogenesis of rheumatoid arthritis (RA) that at several levels has strikingly resemble those of CD: (a) both diseases have strong HLA associations; (b) in both diseases there are infiltration of CD4+ T cells in the affected organs; (c) in both diseases there are do minant immune responses to post-translationally modified antigens; (d) in both diseases enzymes are responsible for the post-translitional modification; (e) in both diseases there is evidence that post-translationally modified antigens bind better to the disease associated HLA molecules and (f) in both disease there are specific auto-antibodies reactive with post-translationally modified antigens. Whereas it is clear that the disease relevant T cell response in CD is directed against gluten, the antigen t hat drives the T cell response in RA is not identified. This projects aims to extend our studies in CD and to take advantage of our knowledge acquired through these studies in parallel studies of RA. We believe that this combined research will lead to dee per insights and facilitate the development of new treatments for CD and RA. In the three coming years we will primarily focus on HLA presentation of posttranslationally modified antigens and study how and where these enzymatically mediated modifications take place.