The risk of rejection after a heart transplant
A heart transplant is a life-saving procedure for patients with end stage heart failure. During this invasive surgery, a patient’s diseased heart is removed and replaced with a donor heart. Even though patients are prescribed immunosuppressive drugs to prevent rejection, up to 20% of patients will still experience acute cellular rejection, also called ACR, in the first year post-transplant. ACR happens when T-cells, which are part of the immune system, begin attacking the new heart, leading to poor outcomes and even death.
Improving on HEARTBiT for ACR classification
A team of HLI and PROOF (Prevention of Organ Failure Centre) researchers have previously developed HEARTBiT, a minimally-invasive, blood-based gene expression “signature” to monitor for ACR after heart transplant. The team sought to improve HEARTBiT’s performance by creating a signature to monitor T-cells in heart transplant patients. There are two primary types of T-cells, namely conventional and regulatory T-cells, that play a crucial role in maintaining the delicate balance of the immune system by exerting opposing forces. Disrupting this balance is believed to contribute to adverse outcomes, such as ACR.
“In our recent study, a key finding revealed that patients who went on to develop ACR within the first year post-transplant had lower expression levels of signature genes associated with regulatory T-cells,” says lead author Ji-Young Kim, PhD.
This work was published in Transplantation.
Predicting rejection status
Using blood samples donated by 94 heart transplant recipients over the course of a year, the group confirmed that T-cell gene expression is different for patients who went on to develop ACR versus those who did not. Combining the T-cell signature with the existing HEARTBiT score resulted in improved accuracy of ACR diagnosis at 70% specificity and 85% sensitivity. As a monitoring tool or a rule-out test, this could potentially reduce the number of required biopsies for heart transplant patients to 4 to 5, compared to the current standard of care which involves 12 to 15 biopsies within the first year following transplantation. The reduced number of biopsies would alleviate the invasive and costly burden of the procedure for transplant patients. More importantly, this study highlights a promising new approach to assess ACR risk in heart transplant recipients.
It is important that these findings are verified using more patient samples. The immediate next step is to confirm the potential clinical utility of the T-cell signature on samples that were collected for a clinical validation study for HEARTBiT.
“This testing would allow us to check how accurate and reproducible the results are from our current study. We are also in the process of assessing whether this new T-cell signature can be useful to predict poor outcomes related to non-optimal immunosuppression in heart transplantation. For example, we could search for kidney toxicity, viral reactivation, and chronic allograft vasculopathy retrospectively in our existing patient cohorts using Providence Health’s new Integrated Health Informatics Datalab (IHID) platform.” – Ji-Young Kim.