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Targeted single nuclei RNA-sequencing for the prediction of heart transplantation rejection

Professor Igor Konstantinov, Institution: Murdoch Children's Research Institute

2018 Vanguard Grant

Years funded: 2019-2020


Patients undergoing heart transplantation require life-long monitoring for rejection. Currently, prevention of rejection is guided by invasive and expensive heart biopsies. The biopsies involve hospital admission, general anaesthesia, radiation exposure, and invasive cardiac catheterization, which are associated with an increased risk of procedural morbidity. The current guidelines specify that 10 biopsies be performed in the 1st year after transplantation, but the prohibitive cost ($7000 per biopsy) and risk associated with biopsies prevents more frequent monitoring. Heart biopsies account for over 50% of the follow up cost in the 1st year after transplantation, and 19% of the cost each year thereafter. Early molecular detection of rejection using a simple blood test would reduce, or eliminate, the need for invasive biopsies, as well as the recurrent anaesthesia and potential morbidity associated with the procedure. Replacing heart biopsies would also result in a 10-fold cost reduction for the healthcare system.

The Royal Children’s Hospital in Melbourne is the nationally funded and designated centre for paediatric heart transplantation within Australia. All children nationwide who receive a heart transplant undergo approximately 10 heart biopsies in the first 12 months after transplantation (the highest risk period for rejection). This provides a unique opportunity to examine alternatives to biopsies in children undergoing heart transplantation.

We have previously developed a genetic test for determining early rejection with approximately 80% accuracy, and identified genetic markers of immune cells that are involved in rejection. In the current study, we aim to build on the previous work by focusing on specific cell populations using a new genetic sequencing technology. This more targeted approach will help us to achieve our goal of 100% accuracy for rejection monitoring, and thus complete elimination of heart biopsies.

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