When someone needs a blood stem cell transplant, the hunt is on for a matching donor. What makes a donor a ‘match’ is largely down to molecules called Human Leukocyte Antigens, or HLA. But HLA has an important role to play in human health beyond stem cell transplants. Find out more in the blog post about the expanding influence of HLA in medicine, and how Anthony Nolan is at the centre of HLA research.
Human Leukocyte Antigen (HLA) molecules are made up of multiple proteins, and our genes carry the instructions to make each of them. Altogether, there are tens of thousands of different versions of these genes, known as alleles, resulting in the potential for many different combinations of HLA. A person’s immune system is ‘trained’ to recognise the cells in their own body, based upon the HLA molecules displayed on the cell surface.
This is why reading the DNA sequence of HLA alleles – known as ‘HLA typing’ – is how donors are matched with patients in need of a transplant. As long as the HLA alleles of the donor closely match those of the recipient, the donor’s immune cells will be well-behaved guests in the patient’s body, tolerating the patient’s own cells. But if the donor is not closely matched, the more likely it is that the donor’s immune cells will attack their host’s body, leading to complications like Graft-vs-Host Disease.
Anthony Nolan and the HLA research community
Dr Sharon Vivers is the H&I Clinical Consultant Lead at Anthony Nolan, and leads the charity’s clinical H&I service provided to 4 UK transplant centres. It’s Sharon and her colleagues in the Anthony Nolan Histocompatibility Lab that will identify each potential donor’s unique combination of HLA alleles, and match this with patients in need of a transplant.
Across the world, more than 35,000 different HLA alleles have already been identified, and new alleles are being discovered all the time. The HLA research community “is built on international collaboration between labs worldwide,” Sharon says.
Whenever a potential new HLA allele is discovered, the DNA sequence is submitted to one central database, the IPD-IMGT/HLA database. And this database, containing sequences of all the HLA alleles that have ever been found worldwide, is maintained by Anthony Nolan scientist Prof Steven Marsh and his team.
“[The database] is so fundamental to what Anthony Nolan does,” Sharon says. “I think it really highlights the importance of what we do as an organisation and how critical we are to the wider H&I community.”
The expanding influence of HLA in health and disease
But the influence of HLA goes far beyond transplant medicine.
There are certain HLA alleles which are linked to immune conditions like coeliac disease and ankylosing spondylitis, so HLA typing can be used to help diagnose these conditions.
A person’s HLA alleles can also influence how they respond to medications. For example, people who are HIV-positive are sometimes treated with a drug called abacavir, but it’s long been known that abacavir causes severe side-effects in those who carry an HLA allele called HLA-B*57:01. Testing for this particular allele therefore helps identify people who should receive a different drug.
And our knowledge of the influence of HLA on drug response is increasing all the time, including in cancer. For instance, a recent study has linked HLA to the effectiveness of checkpoint inhibitors, cancer drugs which are designed to encourage the immune system to attack cancer cells. The study, published in early 2022, found that these drugs are less effective in people who carry an allele in the HLA-A*03 group, found in up to 16% of people. This held true for a range of checkpoint inhibitors and different cancer types.
“I think we will find more and more links between HLA and responses to drugs,” says Sharon, “especially drugs that are treating things like cancers that are associated with immune system.”
Anthony Nolan’s HLA typing services
While interest in HLA is growing, with more than 35,000 different HLA alleles and counting, it can be challenging to carry out HLA typing and interpret the results. Many hospitals and researchers in academia and industry are therefore opting to outsource HLA typing to specialist laboratories.
And because of Anthony Nolan’s expertise and its central position in the HLA community, Sharon believes Anthony Nolan is an ideal partner for HLA typing. The team provides a flexible service tailored to the needs of clients, giving advice in interpreting results and support through the whole process. “Because we are HLA specialists, you get a level of expertise and service that you maybe wouldn’t get elsewhere,” Sharon says.
HLA typing will continue to be a crucial part of transplant medicine, and the work taking place at the Anthony Nolan Research Institute will help more people receive a life-saving blood stem cell transplant. And as we understand more about HLA and its role in diseases, HLA typing will become a crucial part of other areas of medicine too.
“We’re understanding more and more about the immune system, and how it can influence people’s response to disease and the treatments that they’re receiving,” Sharon says. “It’s a really exciting time to be in our field.”
Find out more about Anthony Nolan's HLA typing and other lab services by clicking below.