Torque teno virus: A biomarker of immunosuppression
Research type
Research Study
Full title
Torque teno virus: A biomarker of immunosuppression in kidney transplantation, an objective single centre study
IRAS ID
291391
Contact name
Muhammad Magdi Yaqoob
Contact email
Sponsor organisation
Queen Mary University of London
Duration of Study in the UK
1 years, 11 months, 30 days
Research summary
Summary of Research
Balancing the adverse effects of over-immunosuppression such as infection and malignancy, to the risk of rejection, remains the central challenge for day-to-day clinical practice in transplantation. A quantitative measure of immunocompetence remains elusive, and in absence of such markers, immunosuppression drug concentrations and clinical events, such as organ rejection, infection, malignancy etc. are used as surrogate markers of immunocompetence to guide therapy.
As demonstrated in several studies, the Torque teno virus is widespread amongst the general population. In theory, if one suppresses the immune system, these viruses should multiply, resulting in a higher DNA level which can be detected by a simple blood test. Hence, the DNA level could be used as an indicator for the level of immunosuppression, along with the available blood tests to measure the level of toxicity of the said drugs.
In our research to be done at the Royal London Hospital, we aim to elucidate that the Torque teno virus is widely prevalent in an ethnically diverse East London kidney transplant recipient population by conducting the viral PCR on blood samples already collected during their routine clinic visits. The population will include all kidney transplant recipients in a two-year period. We will measure the correlation between the TTV DNA level and drug concentrations of the immunosuppressive medications which will tell us how the DNA levels are affected by different drug concentrations. We will then measure the correlation between the TTV DNA levels, and the common adverse outcomes experienced by the transplant recipients, namely, patient death, loss of transplant organs, transplant rejection, rates of infection, and cancers in transplant patients by collecting data from patient records. These tests will help us understand whether the Torque teno virus DNA levels can be used as a marker of immunosuppression in the general population in the UK.Summary of Results
The human immune system recognises a transplanted kidney as foreign and can attack it. To protect the kidney, several medicines are used to suppress the immune system. These medicines reduce the risk of rejection, but can increase the risk of infections caused by bacteria, viruses and fungi. Finding the right amount of these medications for each person is therefore extremely important, as too little immunosuppression can lead to the immune system attacking the kidney, while too much can leave the body vulnerable to infections.
At present, the drug levels of some of these medications are routinely monitored and used alongside other clinical information to adjust treatment. However, the level of a drug in the bloodstream does not directly measure how suppressed a person's immune system is. People can respond differently to the same dose, and even to the same blood level of a given medicine. In this situation, a test that gives us more information about the overall effect of immunosuppression could help us tailor treatment more closely to each patient.
Torque teno virus (TTV) is a common virus which is present in most people's bodies and does not normally cause disease. Previous research has suggested that the amount of TTV in the blood changes with the level of immunosuppression. When the immune system is more suppressed, there is more TTV in the bloodstream, as the virus can multiply more freely. TTV levels fall when the immune system becomes more active. This has led to significant interest in the potential role of TTV as an indirect measure of the overall functioning of the immune system.
The main aim of our study was therefore to investigate whether measuring TTV after kidney transplantation could provide useful information about a patient's level of immunosuppression.
We recruited 268 kidney transplant recipients and measured TTV levels in their blood at regular intervals following transplantation. We collected information about infections and rejection events, as well as routine blood test results. We found that TTV levels increased substantially during the first few months after transplantation, under the effect of intense immunosuppression, and then stabilised as immunosuppression was reduced. We also found that changes in TTV levels may be useful for predicting rejection and infection events, particularly BK virus infection. BK virus is usually harmless but can become active after transplantation and, in some patients, damage the transplanted kidney.
The relationship between TTV, immunosuppressive treatment and complications after transplantation is complex. Further research is therefore needed to confirm these relationships in larger studies involving multiple transplant centres.
We would like to thank everyone who took part in the study.REC name
London - Chelsea Research Ethics Committee
REC reference
22/PR/0061
Date of REC Opinion
8 Feb 2022
REC opinion
Further Information Favourable Opinion