Approved Research

Integrative Translational Research in Primary Immunodeficiency (INTREPID)

Lay summary

Background: Primary immunodeficiencies (PID) represent a spectrum of conditions caused by genetic mutations that affect 1 in 350 people in the UK. PID can be incredibly harmful as they disrupt normal immune system functioning and can result in an increased chance of infections and some types of cancer as well as autoimmune and other inflammatory conditions such as allergies.  However, variability in PID symptoms and severity makes it challenging to achieve the specific diagnoses required for the care for individual patients. Scientific Rationale: Previously, we have shown that combining clinical and genetic knowledge of a large cohort of PID patients can reveal new mutations that cause PID in genes that have not been associated with PID before. Interestingly, members of the general population can have the same mutations or mutations in the same gene but can appear healthy, although they may have missing parts of their immune system or an increased risk to certain immune conditions such as autoimmunity. Aim: The proposed study aims to use the data in the UK Biobank to better understand how mutations in these genes  newly-associated with PID can affect how the immune system functions. Public Health Impact: Information surrounding the impact of these mutations on immune function is valuable as this can provide insight into the factors that increase the risk of developing diseases such as autoimmunity and drive how these diseases progress in different individuals. Understanding these factors can then influence how doctors treat their patients and can contribute to the development of new targeted treatments. This is particularly important for immune-mediated diseases such as autoimmunity as they present a growing problem in the UK. Moreover, this research could help PID patients get genetic diagnoses that they may not otherwise receive, which can provide key information regarding the nature of their disease, and lead to more effective treatment plans. Duration: The analysis for this proposed study is expected to 36 months.