The Big 5 Challenges

1. Tolerance

A transplant recipient is thought to be tolerant of the transplant when it works well without rejection while off all immunosuppression. This has long been considered the “holy grail” of transplant practice. But it is becoming a reality by finding the gene sets that are expressed in recipients while off immunosuppression. Hence a “tolerant gene footprint” can be measured and supplemented with functional assays. We are working with a group at Stanford University California to apply these findings to enable safe minimization a recipient’s immunosuppressive drugs. This work may lead to withdrawal of immunosuppressive drugs completely while permanently monitoring the immune response.

2. Chronic rejection

Although management of acute renal allograft rejection has greatly improved chronic rejection is the commonest cause of transplant failure in Australia. Recipient antibodies directed against the transplant play the major role in damaging the transplant. Our group has devised a method to detect this type of rejection in the glomeruli (or filters) of the kidney; this may allow early treatment to be instituted.

3. Ischaemia reperfusion injury

This occurs every time an organ is procured from a donor, preserved and transplanted into a recipient. Although there is improvement in preservation solutions the major treatments remain minimisation of ischaemia times and cold storage. But we have now defined a molecule, Castanospermine that is strongly anti-inflammatory and may protect the organ against this injury. This work will aided by detecting a marker of damage to the kidney, an integrin molecule αvβ6.

4. Organ Supply

The need for organ transplantation in Australia is not being met by current donation rates. From 2009 to 2011, 38% of prospective recipients on the waiting list for organ transplantation at the start of the year or added throughout that year received an organ transplant by the end of that year. The deceased donor rate in Australia in 2011 increased to 15 donors pmp but it was 36 in Spain and 25 in the USA. Amongst the obstacles to donation it is clear that refusal by the potential donor or family remains significant. There is more work to be done to understand this issue and we wish to address it.

5. Side effects of immunosuppression

These are cancer, infection, kidney damage and bone disease. These will be improved by reducing and then withdrawing immunosuppression in a safe way as described above.