Scientists discover role for gene in immune system

3 November 2014

Researchers at the UCL Institute of Immunity and Transplantation (IIT) have discovered that a single gene plays an important role in ensuring humans are able to fight infections.

Professor Bodo Grimbacher, Professor Lucy Walker and Professor David Sansom have discovered that a faulty copy of gene CTLA4 leads to a condition called primary immunodeficiency (PID). 

The discovery, published in the journal Nature Medicine, was made possible because the IIT, which is based at the Royal Free Hospital, places researchers, clinicians and patients together to promote world-class research on immunological disorders.

Patients with PID have an immune system which does not provide them with enough protection from infections. As a result they can suffer from a range of symptoms, including heart problems, repeated bouts of severe infections like pneumonia and skin abscesses. In addition, patients with PID can also suffer from autoimmune symptoms, where the poorly regulated immune system begins to attack the body. 

Although doctors have long known that PIDs are genetic disorders, no one has previously identified a role for CTLA4 in this condition. This new work has revealed that people need two healthy copies of CTLA4 for their immune system to function properly. 

Scientists at the IIT previously discovered that the CTLA4 gene had a role to play in regulating immune cells called Treg-cells, but until now it wasn’t thought that a mutation of this gene would cause PID. 

The discovery means that doctors can diagnose this condition much more easily, using a simple genetic test.

It also means that it could be easier to treat patients with PID. Some patients with PID could be given abatacept, a drug used to treat patients with arthritis, because this drug plays a similar role to the body’s natural CTLA4 and suppresses autoimmune symptoms.

Professor Walker said: “This is a really important discovery. We now understand why there is a problem with the immune system in some patients with PID and that will enable us to develop better treatments.”

Dr Siobhan Burns, an immunodeficiency clinician at the Royal Free Hospital, added: “This discovery has been possible only because of the way the institute places clinicians and researchers close together. The scientists have provided their expertise in terms of identifying the correct gene and looking at its function, while the clinical team have access to the patients.”

Professor Sansom said: “It was important that we had already published papers on the function of this gene, so we had a lot of information about the protein this gene produces and its role in the immune system. Now we have a clearer understanding of what it does in the immune system in people.”


Media contacts: Mary McConnell, email or call 020 7472 6665.

About the UCL Institute of Immunity and Transplantation (IIT)
The IIT serves as a research hub where scientists and clinicians can work together to develop new treatments and improve the care of patients with immune-related diseases like HIV, viral hepatitis and diabetes. It is a project that has been commissioned jointly by the Royal Free Charity, UCL and the Royal Free London NHS Foundation Trust. The construction of a new building to house the IIT on the grounds of the Royal Free Hospital will start in 2015. Once the building is complete, there will be capacity for more IIT research projects and more Royal Free Hospital patients will have access to the latest treatments.

About the Royal Free London NHS Foundation Trust
The Royal Free began as a pioneering organisation and continues to play a leading role in the care of patients. Our mission is to provide world class expertise and local care. In the 21st century, the Royal Free London continues to lead improvements in healthcare. 

The Royal Free London attracts patients from across the country and beyond to its specialist services in liver, kidney and bone marrow transplantation, haemophilia, renal, HIV, infectious diseases, plastic surgery, immunology, vascular surgery, cardiology, amyloidosis and scleroderma and we are a member of the academic health science partnership UCLPartners.

In July 2014 Barnet Hospital and Chase Farm Hospital became part of the Royal Free London.

About University College London (UCL)
Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender, and the first to provide systematic teaching of law, architecture and medicine. We are among the world's top universities, as reflected by performance in a range of international rankings and tables. UCL currently has almost 29,000 students from 150 countries and in the region of 10,000 employees. Our annual income is more than £900 million.