Primary Immunodeficiency: Mechanisms and Diagnosis via Integrative Clinical Immunogenomics

Primary immunodeficiencies (PID) are a group of rare disorders affecting at least 1 in 350 peoplein the UK. PID include a range of genetic diseases that can mean people are at higher risk of getting life threatening infections, autoimmune diseases and some cancers. The large number of different PID symptoms and differences in how bad they can be makes it difficult for patients to be diagnosed and get the right treatment and care.

Recently, we showed that combining clinical and genetic information from 800 PID patients revealed new genetic causes of their conditions and helped diagnosis. The INTREPID project will extend this method by collecting more detailed genetic, clinical and molecular measurements from a bigger group of 2,000 PID patients, and using that information to find out what changes are responsible for specific forms of PID. This will give a genetic diagnosis to more patients and improve our understanding of the human immune system.in the UK. PID include a range of genetic diseases that can mean people are at higher risk of getting life threatening infections, autoimmune diseases and some cancers.

Whole genome sequencing means reading a person’s DNA to get their entire genetic code and this information is important to the success of the INTREPID project. For this project Genomics England are the company carrying out whole genome sequencing and in order to send them DNA samples from PID patients recruited to NIHR BioResource – Rare Diseases, patients will be invited to join the Genomics England National Genomic Research Library (NGRL). Separate consent to join the NGRL is needed to allow Genomics England to make patients’ de-identified genomic and health data (data that does not identify a patient) available to other approved researchers as well as to the INTREPID study team. By sharing de-identified data with more approved researchers there is a greater chance of finding out information that helps the patient and also other patients with the same problems or even different problems.