Molecular Markers of Rejection
Oxford BART Study - Biomarkers that can be used to predict Acute Rejection in Transplantation
The Oxford BART Study is aimed at identifying new Biomarkers that can be used to predict Acute Rejection in Transplantation (BART). A biomarker is an objective measurement in the body that can be assessed in order to inform clinicians about the efficacy of a treatment is or how a disease is progressing.
At the moment, rejection of solid organ transplants can only be diagnosed once the rejection process has already started. There are no means to predict when rejection will take place. The aim of the BART study is to identify biomarkers that will predict the onset of rejection after solid organ transplantation, so that the treatment regime can be altered before detrimental damage to the organ has occurred.
The BART study involves transplant patients, clinicians, nurses and scientists working together. The aim is to enroll approximately 220 transplant patients in the study. Any patient who is receiving either a kidney, kidney and pancreas or a pancreas only transplant can participate in the study.
Participants will be asked to provide blood and urine samples before they receive their transplant and at several time-points afterwards up to 5 years after transplantation. These samples will generally be taken at the same time as other blood tests so that patients will not have to pay extra visits to the clinic. The samples will be analysed using sophisticated laboratory techniques by our team of researchers. Also, material will be stored for use at later time-points throughout the study.
The Oxford BART Study is being led by Peter Friend, Professor of Transplantation and Director of the Oxford Transplant Centre and Kathryn Wood, Professor of Immunology, both from the University of Oxford. The Research Nurse is Sally Ruse. The research scientists involved all work in the Transplantation Research Immunology Group.
CAMPATH-1H clinical trial
Background Peripheral leukocyte depletion at the time of kidney transplantation has been found to be a powerful strategy enabling a reduction in the amount of non-specific immunosuppression required to maintain graft survival. In addition, it has been suggested that depletion of existing immunocompetent leukocytes from the recipient at the time of transplantation may allow reprogramming of the immune system in a way that promotes the development of unresponsiveness or tolerance to the graft. However, this conclusion remains controversial as long term follow up studies assessing the immune status of recipients treated with leukocyte depleting agents have not been performed. Detailed characterisation of the phenotype and function of leukocytes remaining after leukocyte depletion, as well as those repopulating the immune system in the presence of a kidney transplant will allow more accurate post-transplant monitoring. This will enable decisions regarding weaning of immunosuppressive drug therapy in individual patients to be made.
Current work The current project focuses on kidney transplant recipients treated with anti-CD52 depleting antibody CAMPATH-1H (click on image to enlarge) at the time of transplantation followed by reduced doses of immunosuppressive drugs, tacrolimus and mycophenolate mofetil for the first 6 months after transplantation, followed by sirolimus and mycophenolate mofetil thereafter
Specific aims of the project: 1. To determine susceptibility of different subsets of leukocytes (naïve/memory T cells, NK, NKT, B cells, T regulatory cells) and antigen presenting cells (APC – monocytes, myeloid and plasmacytoid dendritic cells) to depletion with CAMPATH-1H in patients who receive a kidney transplant. 2. To evaluate the functional activity of leukocytes that are (i) not susceptible to depletion with CAMPATH-1H and (ii) repopulate the peripheral immune system after transplantation. 3. To determine the functional capacity of the recipient’s APC during the follow-up period. 4. To develop an in vitro assay to model the patient’s susceptibility to immunosuppression. *This research project is carried out in collaboration with Professor Peter Friend.