The first-of-its-kind study uses precision genomics insights to drastically enhance kidney donor matching and patients’ quality of life.
Vancouver Coastal Health Research Institute (VCHRI) researchers are at the forefront of a ground breaking Canadian initiative in precision medicine to enable kidney transplant matching on a new genetic level.
Spearheaded by Dr. Paul Keown, Dr. James Lan and Dr. Karen Sherwood, in partnership with transplant teams across Canada and around the world, this pioneering program heralds the world’s first formal use of prospective epitope-based matching for kidney transplants. The research is backed by a $5.8 million award from VCHRI, Genome BC, Genome Canada, Michael Smith Health Research BC, along with partners in academia and industry.
“We anticipate that our research will diminish both the frequency and severity of rejection, ultimately improving graft survival and reducing the necessity for repeat organ transplants."
Epitopes are crucial segments of human leukocyte antigen (HLA) proteins present in donated organs that also trigger transplant recipients’ immune systems. Matching for HLA proteins has been the common practice up to now, but poses significant clinical challenges due to the vast array of almost 40,000 recognized variations in the HLA genes.
Rejection constitutes approximately half of failed transplants, Lan adds. Transplant patients receive immunosuppressive medications to mitigate the risk of rejection. However, these medications come with side effects that can present challenges of their own, including an increased risk of infection.
“It is clear that the status quo is far from ideal, and has prompted the coordinated research efforts of our team to revolutionize transplantation by the application of precision medicine.”
Epitope-matching research has implications for other solid organ transplants
Matching donors and recipients by epitope dramatically reduced the complexity of the search, as there are fewer than 150 epitopes to consider.
The new epitope matching program offers the opportunity to customize treatments based on each patient's unique genetic profile, with the aim to both reduce organ rejection risks and minimize the toxicity of powerful immunosuppressive drugs, explains Lan.
“Lower drug dosages translate to reduced risks of side effects, including hypertension, diabetes, infections, gastrointestinal complications and certain cancers; thereby, improving overall patient health and well-being.”
This novel program is made possible by dramatic advances in biology and medicine, such as the development of nanopore sequencing technologies that reduce the gene sequencing time from days to hours, says Sherwood.
“While this study is commencing in kidney transplantation, we also anticipate that this research could enable epitope-matching methodologies in heart, lung and other organ transplants, signaling a paradigm shift in transplant medicine.”
