Defining critical pathways of innate immunity for precision therapy of autoimmune diseases

Rheumatoid arthritis Juvenile rheumatoid arthritis and systemic lupus erythematosis are diseases which affect thousands of Canadians and are associated with substantial healthcare costs. They often lead to long term disability, despite improvements in therapy over recent years. These are all diseases in which the normal regulation of the bodies immune system fails. Because of this failure in regulation, the immune system attacks the body causing chronic illness and tissue damage. There are a number of rare genetic disorders which are known to cause similar problems with immune regulation and disease which can provide important clues to how such disease processes work and which genes and regulating pathways are really critical in causing human disease. In our proposed study, a cross country team of clinicians and immunologists will work together to look closely at groups of patients for those with genetic changes associated with altered immune regulation. Using this information we aim to define subsets of patients with closely related defects in immune regulation who would be candidates for therapies that target the function or deficits in immunity associated with their disease. We will also uncover important new information regarding the immune and genetic defects that are found in these diseases since we will be applying a unique combination of analyses to this problem. Through this work we aim to both better target existing treatments to the patients who will respond to them and to uncover potential novel approaches to the treatment of these serious debilitating diseases.