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sector_ico_Health_trans Human Health

Identifying molecular surrogates of optimal immunosuppression by leveraging short- and long-term outcomes in heart transplantation

  • Project Leaders: Raymond Ng, Scott Tebbutt
  • Institutions: Prevention of Organ Failure (PROOF) Centre of Excellence
  • Budget: $247583
  • Program/Competition: Data Access, Integration and Analysis Program
  • Genome Centre(s): Genome British Columbia
  • Fiscal Year: 2022
  • Status: Active

Patients receive heart transplants as a life saving measure after heart failure. Ensuring the success of the transplant is of utmost importance as transplantation is often the last resort for these patients. Rejection is the primary cause for heart transplant failure and consequently, patients must take drugs that suppress their immune system to prevent rejection. Yet there is a fine balance to be achieved in immune system suppression. Too little suppression might lead to rejection of the transplant (both acute and chronic), while too much suppression can cause other serious and life threatening side effects such as infections, kidney problems and even cancer. 

New immunosuppressive drugs to prevent transplant rejection while allowing normal immune function would greatly improve care and patient outcomes. Importantly, this balance is likely to be highly personalized to each individual heart transplant recipient (based on their genetics and other factors). Therefore, there is a great need to develop more effective clinical management tools and tests (for example, using blood-based biomarkers), that can help fine-tune immunosuppression therapy for each individual patient. 

This project builds on many years of measuring the biomarker signatures in blood (gene expression-RNA) donated from hundreds of heart transplant patients. These studies enabled researchers to develop a blood test to monitor for the absence of acute rejection. Now the research team seeks to use data from the Integrated Health Informatics Datalab (IHID) to link this biomarker data with short-term (i.e., infections, kidney injury) and long-term patient outcomes (i.e., chronic rejection, kidney disease, cancers) and develop new biomarker tests that might better predict these poor outcomes. The team’s new biomarkers can be used to better fine-tune immunosuppression treatments on a patient-by-patient basis, to minimize negative health outcomes.