Genetic and Functional Mechanisms of Susceptibility to Infection

Summary

The aim of this study is to understand how the body’s defence system- the immune system, provides protection from infectious disease.

It is known that increased activity of an enzyme called PI3Kδ has been implicated in various common inflammatory diseases and cancers. Patients with such diseases can potentially benefit from treatment with PI3Kδ inhibitors that reduce its activity. However, several clinical studies of PI3Kδ inhibitors failed to show clear benefits. A likely explanation is that these common diseases are heterogeneous and increased PI3Kδ activity is involved in only some of the patients. Therefore, a personalised approach is targeting only patients with high PI3Kδ activity. However, the normal ranges in healthy subjects have not been established, which complicates identification of those with hyperactivated PI3Kδ. To answer this question, this study will assess PI3Kδ activity in a cohort of healthy volunteers. Furthermore, we will look for genetic variants that regulate PI3Kδ and will study immunological biomarkers to understand how they correlate with PI3Kδ activity. Finally, to see if increased PI3Kδ activity is stable over time, we will repeat this analysis in a fraction of the original cohort after 2-3 months. This study will help to understand regulation of PI3Kδ and its impact on the immune system and, in future, will help to identify patients that can benefit from treatment with PI3Kδ inhibitors. Therefore, the information gained from this study will help to better understand why some individuals are at increased risk of infection and how best to protect them.

Organisation:  The Genetic and Functional Mechanisms of Susceptibility to Infection is led by Dr Sergey Nejentsev from the Department of Medicine at the University of Cambridge.

Participation: Volunteers who are enrolled at the NIHR BioResource are invited to participate in the Genetic and Functional Mechanisms of Susceptibility to Infection study. This study was launched in April 2023 with the aim of recruiting 100 volunteers aged 30-70 years old.

The study involves two study visits to the research unit on the Cambridge Biomedical Campus. Each study visit will be 2-3 months apart. Each recruited volunteer will be asked to sign a consent form and donate up to 50 ml of blood. Each volunteer will be pre-screened and assessed for any concurrent chronic disease such as cancer, heart disease and stroke, any auto-immune diseases such as Type 1 diabetes and the use of antihistamines and inhaled/ topical steroids.