Australia joins international team of researchers aiming to revolutionize organ transplant outcomes.02 October 2015
Thousands of organ transplants are performed in Australia every year, however the success rates of these procedures continue to be limited by immunological rejection and other complications. Professor Philip O’Connell of the Millennium Institute, University of Sydney who has led international studies on transplant genetics said “the opportunities to discover important causes and new treatments in transplantation using the new genetics is immense and this study has much to offer our patients”. Australian Genome Research Facility is also participating in the initiative. “We are pleased to support this innovative initiative that will bring together global efforts to harness the power of genomics to address the significant problem of transplant rejection” says Dr Kirby Siemering, Director of Science and Technology.
The data gathered by the researchers during the study will be used to detect genetic factors, in a donor or recipient, which lead to an acute rejection of a transplant. Professor Abraham Shaked, MD, PhD, the Eldrige L. Eliason Professor of Surgery, and Director of the Penn Transplant Institute says. “Transplant outcomes such as acute rejection are likely to be influenced by multiple genetic factors in the donor and recipient, and in order to obtain the statistical power to detect all those factors we need very large datasets that can be appropriately combined.”
The project has grown rapidly in scale since its inception in 2012 and now includes over 35 participating institutions, whose separate studies around the globe have already generated genomics and outcome data for over 32,000 organ donors and recipients.
“We expect to gain many new insights into the biology of transplant rejection, tolerance and side-effects of immunosuppression drugs,” said Dr Brendan Keating, DPhil, an assistant professor of Surgery at University of Pennsylvania and a leader of the study. “That should enable us to make better matches of donors and recipients, to treat and monitor patients more effectively after their transplants, and ultimately to develop better drug dosing to prevent transplant complications and failures.”
"We’re excited to be part of an international consortium like iGeneTRAIN but also to be involved with leading Australian researchers in the field of transplant genomics. To be able to apply our experience in high-throughput genome sequencing technology and analysis tools to the important challenge of transplantation genomics is truly exciting,” says David Miller, Team Leader of Genome Sequencing at the Garvan Institute of Medical Research in Sydney. Stephen Alexander of Children’s Hospital at Westmead also says” these opportunities to study transplants across the world offer new hope to our transplant patients”
The study is co-led by researchers from the Perelman School of Medicine at the University of Pennsylvania and is detailed in papers published in Genomic Medicine and in the journal Transplantation.
For more information:
AGRF media contact:
Dr Kirby Siemering
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Scientists have known for decades that a particular set of proteins, the human leukocyte antigen (HLA) complex, provides a signature that identifies to the immune system the body’s cells as belonging to oneself.
Studies have shown, though, that rejection of transplanted organs can occur even when HLA genes appear well matched between donor and recipient, which points to the existence of additional transplant-relevant genes in other parts of the human genome. These other genes are now known to include those encoding so-called killer-cell immunoglobulin-like receptors (KIR) on “natural killer” immune cells, which are well established to interact with HLA molecules and for which some studies suggest take part in self-recognition and impact rejection of a grafted organ, if donor and recipient KIRs are mismatched. Genes that influence the body’s metabolism of immunosuppressive drugs are also now recognized as likely factors in transplant failures.
The project will initially focus on kidney, liver, heart and lung transplant outcomes. The studies by iGeneTRAIN collaborators are looking for links between gene variants and five common outcomes: survival of the transplanted organ, acute organ rejection, side-effects caused in part by immunosuppressive drugs (including new-onset diabetes after transplant and increased cholesterol and blood pressure), adverse events due to chronic immunosuppressive therapy such as infections and malignancies, and delayed function of the transplanted organ.
The iGeneTRAIN studies are also examining, for each donor/recipient pair, a uniform set of DNA locations, including HLA and KIR regions as well as discovery of additional genetic variants across the whole genome, where gene variants relating to transplant outcomes are likeliest to be found. Keating and colleagues, in the paper published in Genome Medicine have described their specialized genetic array comprising tests for nearly 780,000 genetic variants across each of the human genomes analysed.