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.”