CMV in Transplants
Research type
Research Study
Full title
Analysis of cytomegalovirus pathogenesis in solid organ transplant patients.
IRAS ID
221926
Contact name
Paul Griffiths
Contact email
Sponsor organisation
UCL
Clinicaltrials.gov Identifier
2095, researchregistry2095
Duration of Study in the UK
5 years, 0 months, 0 days
Research summary
Research Summary
Immunosuppressive drugs that prevent the rejection of transplanted organs also reduce immune responses that normally protect patients from virus infections. In previous research, we pioneered a way of detecting the most important virus (human cytomegalovirus; HCMV) in the blood to identify those at risk of disease. Based on our results, prompt administration of antiviral drugs at the first detection of HCMV (pre-emptive therapy) was introduced
into clinical practice and has reduced the serious diseases caused by this virus.
These patients all receive the same immunosuppressive drugs, but only some have HCMV detectable in the blood, showing that they have poor immune control of HCMV. This phenotype could be explained if there were genetic differences in some strains of the virus. We have assembled a multidisciplinary team to assess how HCMV evolves after transplant from one person to another and relate the results to measures of how active different components of the immune system are against HCMV. We will conduct a natural history study, collecting samples of urine, saliva and blood to allow whole genome sequencing of strains of HCMV. Although there will be no benefit for the patients who volunteer for this study, as with our earlier research, we expect the results will explain the phenotypes observed and find immediate practical applications in the management of future patients.Summary of Results
Human cytomegalovirus (HCMV) infection is a lifelong infection with over 50% of the population infected. In healthy people, this is controlled by a robust immune response but in people who are immune-suppressed the virus can replicate and cause disease. This can either be due to a new viral infection or the reactivation of the lifelong infection already in the host. Understandably, in organ transplant patients who are immune-suppressed this is a major problem as are at threat from the donor virus or their own virus.
Despite this potential threat some transplant patients can control HCMV even though they are immune-suppressed. the reasons for this are not fully understood by a number of potential explanations are plausible:
1) even though immune suppressed some patients have sufficient anti-CMV immunity that is functional against the virus
2) even though immune suppressed some patients can make new immune responses against HCMV post transplant
3) some immune suppressed patients are infected with a strain of HCMV less likely to cause disease because it is better controlled by the immune system.Our results so far have identified that the risk of disease is combination of these 3 major hypotheses. Thus we have observed that:
1) patients with immune cells that can control HCMV replication in the lab are better able to control HCMV infection in the body.
2) some patients have immune cells that can recognise HCMV infected cells but are not capable of controlling the virus. These patients suffer from HCMV disease
3) In patients with who have high levels of virus in their blood we see mutations in specific genes of the virus that will allow it to better evade the immune system Additionally, through this work we have generated a better understanding of what a successful HCMV vaccine may look like which we are currently developing with a view to protecting all our vulnerable patient groups (including babies via vaccination of their mothers).Thus these studies have begun to help us understand why some patients can control HCMV without the need for anti-virals and, specifically, which immune responses are important. This will have major importance for the design of new vaccines and immune therapies in the future
REC name
London - Queen Square Research Ethics Committee
REC reference
17/LO/0916
Date of REC Opinion
23 Jun 2017
REC opinion
Favourable Opinion