Using genomic approaches to understand immunogenicity of biologic drugs in inflammatory bowel disease (360G-Wellcome-222850_Z_21_Z)

Inflammatory bowel disease (IBD) is a life-long illness that affects over 300,000 people in the UK. It can cause abdominal pain, diarrhoea and weight loss, and causes significant disability and impact on daily life. There is currently no cure for IBD and without medical treatment, patients may require surgery. Anti-TNF therapies are effective medications for patients with severe IBD, and often used when other treatments have failed. Unfortunately, many patients lose response to treatment over time. A major reason for this is when a patient’s immune system makes proteins (antibodies) that block the effect of the drug (immunogenicity) and reduce its effectiveness. These antibodies can also cause side effects such as skin rash, breathing difficulties and low blood pressure. Understanding why some patients develop antibodies will allow doctors to identify those at risk and prevent this. Using the latest techniques, I will study the interactions between a patient’s genes, their environment, and the way the body reads the genes to identify unique immune system signals that are produced in patients who have developed immunogenicity. Together, this will build an understanding of the immune pathways causing immunogenicity, allowing doctors to target the most effective treatment for individual patients.