A link between kidney transplant rejection and changes in the body’s lymphatic vessels has been discovered in a UCL-led study.
The study, published in The Journal of Clinical Investigation, examined lymphatic vessels in the body’s immune system which help to transport white blood cells and remove waste.
The researchers found that when a kidney transplant is rejected, the lymphatic vessels around the transplanted kidney undergo changes, making it easier for the immune system to attack the new organ.
This discovery could offer a new way of tracking transplant rejection in real-time and allow clinicians to intervene sooner if a donated kidney is in danger of being rejected which might save the organ. Lead author Dr Daniyal Jafree (UCL Great Ormond Street Institute of Child Health) said: “You can think of lymphatic vessels as the kidney’s plumbing system – clearing away excess fluid, immune cells and inflammation.
“Until now, we have struggled to really understand what these vessels do in kidney transplantation because they are so difficult to study. Using new imaging techniques, we’ve shown that these vessels undergo dramatic changes during rejection and are themselves a target of the immune system.”
Transplant rejection is a serious complication, with patients often needing treatments like immunosuppressive drugs to stop their body from attacking the new organ. These drugs can have undesired side effects, so finding a more precise way of diagnosing rejection early could reduce the need for these treatments and improve long-term outcomes for patients. In addition, although kidney transplants initially can have high success rates, roughly 50% of kidney transplants globally fail after a decade.
The team, from UCL, the Wellcome Sanger Institute and the University of Cambridge, used two different methods to reach their findings.
One was single-cell RNA sequencing and the other being advanced 3D imaging. They studied samples from both healthy and transplant rejection patients. Single-cell sequencing allows scientists to study the activity of genes in individual cells, one at a time.
The researchers did this on a very large scale to generate a huge amount of data. Then the team stained large chunks of kidney tissue while still intact and used a procedure to make it transparent. This 3D imaging helped confirm the predictions from the single-cell genetic analysis.
Co-senior author Professor David Long (UCL Great Ormond Street Institute of Child Health) said: “Our innovative methods have allowed us to clearly demonstrate the important role of lymphatic vessels in transplant rejection. By combining single-cell sequencing with advanced 3D imaging, we’ve made a significant step forward in kidney transplant research.”
The researchers found that during kidney transplant rejection, the lymphatic vessels within the transplant change their shape and organisation.
The vessels spread into deeper parts of the kidney known as the medulla, which normally has no lymphatic vessels within it.
At the same time the cell junctions, which are protein anchors that connect cells, go from looking like loose buttons to tightening up like zippers. This is a change that in other contexts is associated with immune cells getting trapped and unable to escape.
The findings suggest that if doctors can detect changes in the lymphatic vessels before rejection becomes severe, they might be able to intervene sooner, preventing organ loss and improving the chances of a successful transplant.
The researchers hope that their findings will lead to advances in transplant medicine, not just for kidneys but also for other organs.
LinksImageCredit: Nadzeya HaroshkaMedia contact:Laura Hannam