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What did the project achieve?
“We’ve developed and tested a sophisticated new way to gauge how well a child’s immune system is rebuilding after antiviral treatment for HIV or a stem cell transplant to treat an inherited immunodeficiency,” says Professor Robin Callard of the UCL Great Ormond Street Institute of Child Health. “This will give doctors crucial knowledge that will help them to ensure each child has the best chance of a long-term recovery.”
Children who have a poorly functioning immune system, either because of an infection, such as HIV, or due to an inherited condition, are at high risk of life-threatening infections. Modern therapies – such as antiviral drugs, stem cell transplants and gene therapy – are giving hope to affected children, at least in the short term. But exactly how well they work as children grow older – and particularly when they become adults – is largely unknown.
It’s critical that doctors can get accurate information about how well a child’s immune system is recovering after therapy – so they can modify treatment to make sure their immune system is as strong as possible for fighting infections and preventing cancers in later life.
Professor Callard and his team have developed new methods based on the latest DNA sequencing technologies and data analyses, to enable doctors to monitor how quickly important immune cells called T cells recover and become effective.
“We have set up and optimised our new technique – and successfully tested it on children who have either received a stem cell transplant or antiviral therapy,” says Professor Callard. “Our results show it can accurately measure how well a child’s immune system is recovering much earlier and more comprehensively than current techniques.”
The method is now set up and could be used to measure T cell recovery in children receiving treatment at Great Ormond Street Hospital.
“We hope this will be tremendously useful for doctors – improving their ability to make treatment decisions, such as the choice of drugs to give a child with HIV, or the best source of stem cells to use for a transplant,” says Professor Callard.
This research was completed on
Some children have weakened immune systems, making them vulnerable to infection and putting their lives at risk. This includes children with HIV, and children with severe immunodeficiencies and some blood cancers who need a stem cell transplant to restore their immune system. Although treatment helps strengthen the immune system, some children remain unusually susceptible to infection. Professor Robin Callard, of University College London’s Institute of Child Health, is investigating why. His findings could enable doctors to identify the best possible treatment for each individual child, so they have the highest possible chance of escaping infection and remaining healthy.
How are children’s lives affected now?
“Our immune system protects us from infection,” says Professor Callard. “Cells called T cells play a central role. Most of us have a huge repertoire of more than 10 million different T cells. This enables our immune system to recognise and destroy the many different viruses, bacteria and parasites that we might be exposed to throughout our lives,” says Professor Callard.
The diversity in our T cell population is important, because cells that recognise the chicken pox virus, for example, would not necessarily recognise the measles virus.
Unfortunately, some children have greatly reduced numbers of T cells, meaning they are more susceptible to infection. This includes children with HIV and children who have had stem cell transplants for some cancers or severe immunodeficiencies.
“Successful treatment can return T cell numbers to normal,” says Professor Callard. “However, it’s unclear what sort of treatment is best at restoring the diversity in the T cell population. Without that diversity, children remain vulnerable to infection.”
How could this research help?
Professor Callard aims to improve the long-term health of children with HIV, and children who are undergoing stem cell transplants, who have weakened immune systems.
“We are studying how children’s immune systems respond to treatment, using blood samples from around 1,000 children from the UK, Europe and Africa,” says Professor Callard. “We are assessing how the number of T cells increases with different approaches to treatment and whether the diversity in the T cell population is restored. Both factors are important.”
“Our findings could enable doctors to identify the best possible treatment for each individual child,” continues Professor Callard. “They may reveal, for example, how old children with HIV should be when starting antiviral treatment, the most appropriate drugs to use, and whether it helps to take a break from treatment. The ultimate goal is to optimise the long-term health of the immune system, giving children protection from infectious diseases throughout their lives.”
| Project Leader | Professor Robin E Callard PhD BA(maths) DSc |
| Project Team | Professor Nigel Klein PhD FRCPCHDr Mike Hubank PhDProfessor Paul A Veys MB BS FRCP FRCpath FRCPCH |
| Project Location | Great Ormond Street Hospital for Children, London |
| Project Location Other | Bone Marrow Transplantation, Great Ormond Street Hospital for Children NHS Trust |
| Project duration | 2 years |
| Date awarded | 25 July 2014 |
| Project start date | 7 September 2015 |
| Project end date | 6 September 2017 |
| Grant amount | £137,569 |
| Grant code | GN2263 |
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