A/Prof Tom Kotsimbos
discusses his work with Tom Whitty
 

What lead you to the field of lung transplant research?

I have always been fascinated by how the body knows what “self” is because this determines what “non-self” is and hence is the first step to how we deal with foreign organisms, antigenic proteins and even transplanted organs.

In evolutionary terms, the immune system has been primarily driven by how to best deal with invading infectious organisms. In this setting, a strategy of rapid attack and targetted destruction is very useful. This is of course exactly what we don’t want to happen with a transplanted organ and is the basis for using strong immunosuppressing drug regimens.

Hence, the paradox for the transplant physician: too strong an immune system and we run the risk of graft rejection; too weak an immune system and there is an increased risk of infection.

What have you learnt about organ rejection?

There are many things but a major insight has been that the optimal immunosuppression “set point” varies between transplant recipients and even differs across time depending on the specific context. Hence, although routine protocols are very important and necessary in the first instance, an individualised approach to preventing and managing organ rejection is best.

In addition, there is an interplay between organ rejection and infection that has important pathobiologic, diagnostic and therapeutic implications.

What changes have you seen?

Individualising our approach for the specific transplant patient taking into account their previous history, current health status and response to prevention/treatment strategies.

This has been dramatically aided by the increased range of immunosuppressant drugs available [often with fewer-or at least different- side effects], better diagnosis, quantitation and management of infection risks post transplantation, and an improved range of management options for a number of difficult but not necessarily common complications that can occur in the lung transplant recipient.

In addition, there has been a steady growth in the size and professionalism of the transplant team all of whom are focused on getting the transplant recipient through the whole process from waiting list, to surgery, right through to the next 10-20 years with a little luck.

What big developments have come about with your research?

The main developments relate to how we best think about and approach the paradox relating to rejection and infection post transplantation and the potential interplay between them. With this in mind, more immunosuppression is not always better as it significantly increases the risk of reactivation of ubiquitous DNA viruses such as CMV (which was the major infection problem in the early era of lung transplantation), as well increasing the risk of many other episodic infections (especially community respiratory viruses).

We were one of the first groups to develop molecular techniques to detect and quantitate viral pathogens in the lung transplant setting and to relate these findings to poorer long term outcomes. This led to improved viral monitoring and antiviral prophylaxis strategies in all our patients. We have now moved on to measure the specific cells of the immune system that control specific viral infections such as CMV and used this information to develop several strategies to measure the specific immune cells that attack the allograft.

In addition we have started to also look at a group of specific immune cells called regulatory T cells that may provide a natural “brake” to the system and lung specific repair cells both of which are likely to be very important in the “bigger picture”  of  what happens to the lung allograft over time.
 
How has technology helped your research?

New technologies have allowed us to measure things we previously never could. This applies equally to new molecular diagnostic assays for viral detection and quantitation, new methods to detect specific immune cells from various body compartments and even new assays to better measure specific drug levels.

In this way, we have improved the quality of the information that we can use to both ask and answer specific research questions.

How has Margaret Pratt Foundation funding helped?

It has substantially helped fill the gap between getting an idea started and seeing it through to a meaningful conclusion. It helps add to the momentum of the whole research effort.

Are we any closer to solving what causes rejection?

We are starting to unravel why some people do well and others do not. We are still a long way from the end however, but at least we know many things now that we previously had no idea about.

In the beginning we had quite a simplistic approach to rejection, so it is somewhat paradoxical that as we have become smarter we are now in a position to understand that there are many things about this process that we  really don’t understand.

But this of course is the first step to a deeper understanding……..or at least we hope so!

Tom is married, speaks 3 languages and enjoys travelling and playing sport with his 4 children. He’s even been a soccer coach!