Grant: Team: Human Immunology Research Teams- Autoimmune diseases related to IMHA pool

Rheumatoid arthritis (RA) is a common autoimmune disease that causes progressive damage to the joints. It is known that individuals destined to develop future RA have autoantibodies (Ab) in their blood that are detectable months to years before the disease actually starts. Our studies have shown that RA is very common in some First Nations families, and that this is based on complex and unique interactions between genetic and environmental factors. Since 2005, we have worked in partnership with several First Nations communities and followed more than 750 unaffected family members of RA patients to determine their risk of developing future RA. To date, 20 individuals have developed RA, indicating a rate of ~1% new cases per year in the family members. We found that the detection of RA Abs in the blood does increase the risk of future RA, but we also show that most individuals with these Abs do NOT develop RA. This compelled us to find ways of predicting future RA that are based on a better understanding the immune system abnormalities that occur during this preclinical stage, and how these changes advance over time in some individuals but not others. With this knowledge, our ultimate aim is to find effective and safe ways to reduce RA risk in these predisposed individuals. Based on existing human and animal model data, we think that a dietary supplement of the spice turmeric, which contains the active ingredient curcumin, has the potential to safely reduce RA risk by modifying the immune changes that lead to RA. Omega-3 fish oils and adequate vitamin D blood levels seem to help the curcumin even further to achieve this. We therefore propose a clinical study to test this in individuals who have RA Abs but have not developed RA. We will use state-of-the-art immune tests to let us know whether there has been some correction of the abnormalities in treated individuals. We also hope to understand how First Nations People view clinical trials that aim to prevent disease