Primary immunodeficiency: mechanism and diagnosis via integrative clinical immunogenomics

Primary immunodeficiencies (PID) are a group of rare disorders that affect at least 1 in 350 people in the UK. PID encompass a spectrum of genetic diseases that can underlie susceptibility to life-threatening infections, autoimmune diseases and some cancers. However, variability in PID symptoms and severity makes it challenging to achieve the specific diagnoses required for the care for individual patients. 

We have shown that combining clinical and genetic knowledge of 800 PID patients reveals novel genetic causes and aids diagnosis. Using this expertise, we will extend this approach by increasing the depth of genetic, clinical and molecular measurements collected across an expanded cohort of 2,000 people with PID, and combine these measurements to characterise the molecular events that are responsible for specific forms of PID. 

This research will provide genetic diagnosis to more patients and will help develop new treatments by increasing our understanding of the human immune system.