Each year, around 1500 Australians are saved through organ transplants, but the risk of organ rejection is still high. This occurs when the immune system views the transplanted organ as foreign and begins to attack it.
Now, researchers from the University of Sydney and Monash University have identified precise molecular targets for organ rejection in mice, providing pathways to improve long-term immune monitoring in clinical transplant recipients.
“While the early outcomes of organ transplants are excellent, the long-term results aren’t nearly as good, with many people losing their transplant within 10 to 15 years,” said senior author Associate Professor Alexandra Sharland, from the University of Sydney.
Presently, clinicians can only detect organ rejection once damage has already been done, and sometimes this damage is irreversible.
However, identifying molecular changes before damage occurs may help prevent this damage in the first place.
“The findings of the pre-clinical study in mice could, if transferable to humans, have significant implications for clinical transplant management,” says Associate Professor Helen Pilmore, President of the Transplantation Society of Australia and New Zealand.
“We hope that one day this research could lead to a simple blood test that is able to distinguish the donor reactive T cells – that is the cells that can specifically recognise the transplanted organ as foreign and respond to it – from all the other cells,” said co-author Dr Nicole Mifsud, Group Leader of the Clinical Immunology Laboratory at the Monash Biomedicine Discovery Institute.
“This could potentially be used to identify which patients are at risk of rejection, or to accurately adjust the level of immunosuppression, the drugs used to lower the body’s ability to reject the organ. Using the appropriate level of immunosuppressants can prove vital to maintaining the viability of transplanted organs.”
Organ transplant at the molecular level
When it comes to organ rejection, it’s all about what T cells – immune cells that recognise and attack foreign antigens – deem a threat.
The team found that the T cells in mice mostly recognised self-peptides (short fragments of proteins produced inside cells) in association with foreign MHC molecules – a molecule on the outside of cells that differs between donor and recipient.
They found that as few as five of these different molecular complexes were responsible for the bulk of T cell recognition. Monitoring the abundance of these particular ‘problem’ molecules could flag the likelihood of organ rejection.
Now, the researchers will investigate whether this same phenomenon applies to human T cells, in order to develop a clinical diagnosis technique for human patients.
Deborah Devis is a science journalist at Cosmos. She has a Bachelor of Liberal Arts and Science (Honours) in biology and philosophy from the University of Sydney, and a PhD in plant molecular genetics from the University of Adelaide.
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