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New study to understand how the immune system is involved in kidney transplant problems

15 February 2022

Thanks to our funding, Dr Sarah Gleeson from Imperial College London will investigate why the immune system can sometimes attack a transplanted kidney to try to understand whether there is a way to diagnose this immune attack early on before irreversible damage is done. 

Dr Sarah Gleeson in her lab
Dr Sarah Gleeson, Imperial College London

The immune system can target a new kidney

When the immune system recognises something foreign inside the body it reacts by activating cells and making proteins called antibodies to attack the foreign object. This is usually a good thing as it protects our bodies from bacteria and viruses, but it can cause complications when it comes to organ transplants. After having a transplant, patients must take drugs to stop the immune system from recognising that the new kidney is foreign and rejecting it.

Glomerulonephritis is an autoimmune disease where the immune system attacks the kidney. In some cases, glomerulonephritis can return after kidney transplant and occasionally it can happen for the first time after a patient has received a new kidney. In these cases, it can lead to the new kidney being rejected. These diseases are often diagnosed quite late, after substantial damage has already been done to the kidney.

Finding out why autoimmune problems happen in certain patients

Using a clinical database with information about 2500 patients who have had a kidney transplant, blood samples from patients before and after transplant, and post-transplant kidney biopsies, Sarah will study what causes these autoimmune problems after kidney transplant and why they only affect certain patients. She will then investigate whether there is a way to diagnose these diseases early on before irreversible damage is done. To do this, she will study three types of markers of disease:

  • Protein markers: Sarah predicts that two particular candidate proteins may be useful in diagnosing post-transplant glomerulonephritis early and she will investigate the levels of these proteins in patient blood samples.
  • Antibodies: Sarah will use a special device to test what type of antibodies are present in patients with post-transplant glomerulonephritis.
  • Structural markers: Sarah will also investigate a phenomenon called tubuloreticular inclusions. These are small structures that can be seen on kidney biopsy samples using a special powerful microscope. They can be seen in some patients who have other autoimmune diseases such as lupus, and Sarah will investigate the outcomes of patients who have these structures.

What does this mean for kidney patients?

Together, the results from this study have the potential to arm healthcare professionals with the information needed to be able to predict the onset and the outcomes of glomerulonephritis in patients who have had a kidney transplant.

“I’m delighted to have been awarded a Kidney Research UK Training fellowship,” said Sarah. “This will allow me to complete a PhD looking at autoimmunity following transplantation. Working with Kidney Research UK to study this further will allow us to more fully explore potential causes and treatments, and will set me on a path to become a clinical researcher”.

Sarah’s work is funded by a Clinical Training Fellowship from Kidney Research UK for £178,000. 

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