Immunological signatures and B cell biology of graft injury following lung transplantation
Lead Research Organisation:
Imperial College London
Department Name: Infectious Disease
Abstract
This funding application is for a 2-year extension to the MRC CARP (MR/V037315/1) project. This project aims to understand more about how transplanted lungs are damaged by infection.
Survival following lung transplant is low compared to liver/kidney transplants. The most common causes of death are infection and chronic lung allograft dysfunction (CLAD). CLAD is often called "organ rejection". It is now understood however that this is an over-simplification. Infection can cause CLAD. Infection is far more common in transplanted lungs than in other transplanted organs because lungs are exposed to the air. It is a major reason why survival rates are lower in lung transplant patients.
Some lung transplant patients live healthily for many years without developing CLAD. Other patients seem much more likely to develop CLAD. Doctors do not know why this is. Some patients develop CLAD in response to infection, but others do not. Limited understanding of the causes of CLAD makes it very difficult to treat.
The immune system of the body produces immune cells. These cells can fight infection and reject transplanted organs. The original project used state-of-the-art techniques to measure over 2000 immune cell markers in blood samples and lung washings from lung transplant patients. It found important differences in how immune cells respond in patients who have CLAD or infection and those who do not. These early results strongly suggest it will be possible to predict who will develop CLAD and, importantly, identify if the cause is due to infection.
This is potentially game changing. However, these initial results need to be confirmed. An additional two years of funding will allow this to be done. The plan is then to set up a large UK multi-centre trial. This will tell us if predictive immune tests for CLAD can be developed for clinical use.
The second important finding from the original project involves a group of immune cells called B cells. B cells can produce antibodies which may damage transplanted organs. They may also protect transplanted organs. Data from the original project suggests a new and unexplored link between lung infection and CLAD and B cells. A 2-year extension to the project will allow us to explore this link in much more detail. It is hoped that this will tell us what these B cells are doing and whether their roles are protective or damaging to the lung. This could lead to new forms of treatment. There are many different drug and cell therapies that are already used to treat B cell disorders. Understanding the roles of B cells in organ rejection may allow repurposing of existing medicines. This means that treatments for other conditions might be used to help transplant patients. It is likely that lessons learned from this project will have far reaching implications for other forms of solid organ transplant and infectious diseases.
Survival following lung transplant is low compared to liver/kidney transplants. The most common causes of death are infection and chronic lung allograft dysfunction (CLAD). CLAD is often called "organ rejection". It is now understood however that this is an over-simplification. Infection can cause CLAD. Infection is far more common in transplanted lungs than in other transplanted organs because lungs are exposed to the air. It is a major reason why survival rates are lower in lung transplant patients.
Some lung transplant patients live healthily for many years without developing CLAD. Other patients seem much more likely to develop CLAD. Doctors do not know why this is. Some patients develop CLAD in response to infection, but others do not. Limited understanding of the causes of CLAD makes it very difficult to treat.
The immune system of the body produces immune cells. These cells can fight infection and reject transplanted organs. The original project used state-of-the-art techniques to measure over 2000 immune cell markers in blood samples and lung washings from lung transplant patients. It found important differences in how immune cells respond in patients who have CLAD or infection and those who do not. These early results strongly suggest it will be possible to predict who will develop CLAD and, importantly, identify if the cause is due to infection.
This is potentially game changing. However, these initial results need to be confirmed. An additional two years of funding will allow this to be done. The plan is then to set up a large UK multi-centre trial. This will tell us if predictive immune tests for CLAD can be developed for clinical use.
The second important finding from the original project involves a group of immune cells called B cells. B cells can produce antibodies which may damage transplanted organs. They may also protect transplanted organs. Data from the original project suggests a new and unexplored link between lung infection and CLAD and B cells. A 2-year extension to the project will allow us to explore this link in much more detail. It is hoped that this will tell us what these B cells are doing and whether their roles are protective or damaging to the lung. This could lead to new forms of treatment. There are many different drug and cell therapies that are already used to treat B cell disorders. Understanding the roles of B cells in organ rejection may allow repurposing of existing medicines. This means that treatments for other conditions might be used to help transplant patients. It is likely that lessons learned from this project will have far reaching implications for other forms of solid organ transplant and infectious diseases.