Grant: CIHR Fellowship

Rheumatoid arthritis (RA) is a chronic, incurable disease with painful symptoms including joint stiffness and swelling affecting more than 300 000 Canadians. We know that this disease is caused by the antibodies of the immune system attacking the lining of the joints, but we do not know why some people develop the disease and others do not. White blood cells, called antigen presenting cells, have proteins, called the neonatal Fc receptor (FcRn) and Fcgamma receptors, which are responsible for responding to antibodies that are produced during an immune response. The FcRn and Fcgamma receptors were once thought to play separate roles, but our research indicates that these proteins co-operate to orchestrate an effective immune response. We are studying how these proteins interact, and how the FcRn could predispose people to develop RA, when they possess a variation in a gene that encodes for a specific Fcgamma receptor, the FcgammaR3a. We will test whether a new medication that blocks the FcRn can be beneficial in mice which have been genetically engineered to have the FcgammaR3a variation and predisposed to RA. These studies will help us understand basic biological mechanisms involving the FcRn and FcgammaR3a, which will help us understand why people with the FcgammaR3a variation develop rheumatoid arthritis or other autoimmune diseases. Our research may lead to personalized medical treatments for rheumatoid arthritis, which will depend on a person's genetics.