Evaluation of tissue specific T cells in GI GvHD
Research type
Research Study
Full title
A pilot study of a flow cytometry based assay to detect a4ß7 integrin expressing T cells and investigate their use as predictive biomarkers of acute Gastrointestinal graft versus host disease (GvHD) in T-depleted stem cell transplantation
IRAS ID
171120
Contact name
Andrew Clark
Contact email
Sponsor organisation
NHS Greater Glasgow and Clyde
Duration of Study in the UK
1 years, 4 months, 1 days
Research summary
Haemopoietic stem cell transplantation is often the only curative procedure for patients with advanced leukaemia and other blood cancers but the effectiveness of transplant can be reduced by tissue damage caused by the new immune system- which can kill patients who have otherwise been cured of their malignancy. The purpose of this study is to investigate whether we can develop a simple new blood test that can help identify patients at risk of developing gut GvHD after transplantation. In the future, this may help to use targeted treatment at an early stage in the disease.
T cells are a kind of white cell and they are an important part of our immune system. They help the body to detect things that are foreign, such as viruses, and then destroy them. After a stem cell transplant, T cells from the new immune system (the graft) can malfunction and attack the body (the host). This is what happens when graft versus host disease (GvHD) develops. The body tissues most affected are the gut, the liver and the skin. We know that each organ has it’s own T cells- so there are gut T cells, skin T cells and liver T cells. In order for our bodies to send the right T cells to the right part of the body, to do their jobs day to day, T cells have receptors (proteins) on their surface. Some of these receptors act like an address on an envelope and tell the body’s postal service where they should be delivered i.e to the gut or the liver or the skin. Once they get to the outside of the gut or liver or skin other receptors on the T cells interact with proteins on the gut cells in a specific way – they open the doors to the inside of the gut, for instance, as a key only opens a single lock. In this way T cells are directed to their specific tissues and allowed into these specific organs where they do their work. In gut GvHD we think that there is a rise in gut specific T cells that occurs 1-2 weeks before patients develop gut symptoms of GvHD. We want to see if we can identify these cells using flow cytometry.
Flow cytometry is a laboratory technique that can identify liver or gut or skin T cells by identifying the receptor combinations present on their surface, using fluorescent antibodies ( smart bombs that target only one receptor) and a laser ( that makes these antibodies shimmer if the cells have the appropriate receptor). While we know what combination of receptors are on the surface of T cells that home into the gut, we do not yet know whether we can identify these cells following a transplant because the immune system has been thrown into confusion after the transplant, there are very small numbers of these T cells present at any one time and they spend most of their time in the tissues and not in the blood.
The first purpose of this study is to investigate whether we can use flow cytometry to identify gut specific T cells that may be causing gut GvHD, using a simple blood test, and show these cells are increased in patients wIth gut GvHD. If we can identify these T cells and show that patients who develop gut GvHD have higher levels than those who don’t, we can use this test as an assessment tool for identifying patients at highest risk of developing gut GvHD and treat them earlier (in future studies not this one – here there is no therapeutic intervention). American investigators have been able to do this, but in a slightly different type of transplant- so we are confident this will be possible.
In the second part of our study we want to use the same test to see whether the grafts that some people have received contained more of these gut specific T cells than others. If they do, we want to see whether this means that recipients of those grafts with higher levels of T cells destined for the gut had a higher likelihood of developing gut GvHD. This has not been looked at before ( because it has been assumed that the only determinant of the damage an individual graft may cause is how that graft behaves in the recipient after it has been transplanted. In this theory all gut homing cells are produced in the host- whereas we are looking for an inherent predisposition to do damage in some grafts- based on the cells they already contain). There are now several other studies showing that differences in the cellular composition of different people’s grafts can have major impacts on how they behave when they are transplanted into patients.
REC name
Yorkshire & The Humber - Sheffield Research Ethics Committee
REC reference
15/YH/0556
Date of REC Opinion
7 Dec 2015
REC opinion
Favourable Opinion