The Science Behind Second Chances: Inside Vancouver General Hospital’s Immunology Lab

When a prospective transplant recipient walks into one of the province’s transplant hospitals, they are met with a team of robustly qualified clinicians. But what many people may not know is that there is a team of dedicated behind-the-scenes laboratory professionals and scientists whose work is crucial in maximizing successful outcomes for organ transplantation. In the Vancouver General Hospital Immunology Lab, Lab Director and ODTRF Scientific Advisory Board co-chair Dr. James Lan and his team work tirelessly—the lab runs 24/7—to match donor organs to the right recipient.

Dr. Jenny Tran serves as director-in-training and clinical scientist for the Immunology Lab. In a recent conversation, Dr. Tran offered a glimpse into the remarkable work of the Lab, describing the highly specialized testing performed before a transplant can proceed. According to Dr. Tran, to match a donor organ to a recipient, she and her colleagues perform “genetic Human Leukocyte Antigens or HLA testing on the donor.” HLA are proteins found on the surface of most cells in the body that help the immune system distinguish between the body’s own cells and foreign cells. When HLA proteins identify something as foreign, they trigger an immune response. In organ transplantation, differences between a donor’s and recipient’s HLA proteins can lead the immune system to attack the transplanted organ, contributing to rejection over time. In more extreme cases, pre-existing HLA antibodies can even cause hyperacute rejection, where the immune system attacks the new organ almost immediately after surgery. Dr. Tran further explains that “we genotype [donors] DNA at the HLA genes, and then we run an antibody test on potential recipients to see whether or not they have donor specific antibodies or DSA.” This is a critical step in initiating the transplant process. Once compatibility has been assessed, the results are shared with transplant programs and BC Transplant, helping connect the right donor with the right recipient as quickly and safely as possible

Collaboration Over Competition: Research That Takes Matching to the Next Level

Clinical scientists such as Dr. James Lan—a multi-time recipient of ODTRF’s seed funding—are continuing to investigate advancements that might ensure longer-lasting graft success. Despite significant advances in transplantation science, about half of organ transplants fail. Dr. Tran commented that “for certain patients, matching might be more important, such as in children, because they’ll likely need more than one transplant over the course of their lives.” Thankfully, the researchers in the Vancouver General Hospital Immunology Lab do not work in a competitive silo. Instead, Dr. Lan and his team are working in collaboration with other researchers across Canada, and internationally, to pursue less-invasive post-operative care.

For example, advancements in recipient genetic testing could allow clinicians to take a more personalized approach to the administration of post-operative immunosuppressant drugs. Rather than using a “one-size-fits-all” approach, personalized medicine recognizes that patients can respond differently to the same treatment, factoring in an individual’s unique characteristics, such as genetics, biology, lifestyle and environment. While the quality of the match between recipient and donor may lead to lower immunosuppressant doses, the clinical administration of both induction therapy and post-operative immunosuppression drugs is still otherwise not highly personalized in most cases.

Current research, however, is improving matching and potentially minimizing the need for long-term steroid use through analysis of HLA proteins on a more granular level. Quite recently, Dr. Tran explained, the Lab “went live with Oxford Nanopore Technology, where we can sequence one person’s HLA genes within hours.” This technology supports efficient and highly personalized matching, which also improves post-operative care, with the goal of less steroids, which are hard on a patient’s body.

Dr. Tran commented that current research—often enabled by funding from organizations such as the ODTRF, Vancouver Coastal Health Research Institute, and Genome Canada—is delving into vital methods to enhance patient care. She described that Dr. Lan “and a group of us [at the Immunology Lab] are collaborating with Alberta to study [donor-derived] cell free DNA testing”. This type of assessment can fast-track physicians’ assessments of the health of a donated organ, before it fails. “Biopsies can be invasive…and sometimes you have a biopsy, and it may be too late, where failure may have already begun to occur,” Dr. Tran explains. With the goal of minimizing invasive biopsies, and to gather data prior to organ failure, a recipient’s blood can be tested periodically to assess whether donor cells are detectable in their blood stream. This “non-invasive biomarker,” according to Dr. Tran “will be like an early marker that physicians can use to get a glimpse of something that might not be great that’s going on.”

Turning Possibility into Reality

For Dr. Tran, the work of the transplant immunology laboratory is about helping make life-changing transplants possible, even if patients may never meet the team behind the scenes. The laboratory plays a critical role throughout the transplant journey—from pre-transplant assessment and waitlist management to organ matching and ongoing post-transplant care. What she finds most rewarding is knowing that behind every successful transplant is the potential for a renewed future, and that the laboratory’s work helps turn that possibility into reality. She is especially proud of the team’s contribution to innovative programs such as Willing-to-Cross and ABO-lite, which create new opportunities for patients who have traditionally faced greater barriers to transplantation. Knowing these initiatives are translating into real-world impacts and giving patients renewed hope is what makes the work so meaningful.