Matching solid organ and bone marrow transplant donors and recipients requires rigorous testing to ensure success.
Milwaukee Municipal Court Judge Derek Mosley, JD, has a special bond with his colleague, Judge JoAnn Eiring, JD. In 2014, Derek was diagnosed with end-stage renal disease and needed a kidney transplant to survive. JoAnn got tested to see if she was a match. “I was brought up that it’s better to give than get, and who wouldn’t want to help their friend,” she said.
Derek spent two years on dialysis before he finally received the news that JoAnn was a direct match. In July 2016, he received his new kidney and returned to full health. He was lucky to find a living donor; many other patients like him rely on the national organ donor registry for their perfect match. But these patients all have one thing in common: the monumental amount of work that goes on behind the scenes to ensure they receive their lifesaving gift.
Versiti is the first blood center in the United States to operate both a tissue bank and organ procurement organization (OPO), which is responsible for facilitating organ donor/recipient matches throughout southeastern Wisconsin. In addition to their work with organ donor families, this team works closely with Versiti Diagnostic Labs’ Histocompatibility & Immunogenetics Laboratory, often referred to as the human leukocyte antigen (HLA) lab, which supports solid organ and bone marrow transplantation through sophisticated testing to match donors and recipients. “Pre-transplant, we try to pair up the best people in order to maximize the likelihood for long-term success,” said Senior Director, Histocompatibility & Immunogenetics Jennifer Schiller, PhD, D(ABHI).
HLA and solid organ transplantation
The HLA system is comprised of a group of proteins that are responsible for the regulation of the immune system. When it comes to solid organ transplantation, it is important to examine the HLA of donors and recipients in order to avoid pairs with donor-specific antibodies that may make a donor organ incompatible. “The testing we do for all solid organ transplantation is focused on understanding the HLA genes that the donors and the recipients have, and the HLA antibodies that a recipient already has,” Dr. Schiller said. “We use that information to determine the compatibility between the two and assess the potential risk of the recipient accepting versus rejecting an organ.”
In addition to advanced testing for transplant recipients and urgent testing for deceased donors, the HLA lab conducts testing at the time of transplantation and post-transplant monitoring to understand if transplant recipients produce new or stronger HLA antibodies. “If there is a problem post-transplant, we can see if it’s antibody mediated or cell mediated,” Dr. Schiller said. “We can determine what arm of the immune system is causing the rejection and recommend a course of therapy depending on what is happening immunologically.”
Though this testing often results in long, on-call hours, Dr. Schiller says the payoff is hearing about the transplant success for the patients that her team helps. “It’s rewarding because you see people who are on the waitlist for a particular organ—sometimes, for a very long time—and when the right match comes up and you get that person through the transplant and monitor them afterward, you know that you’ve made an impact in somebody’s life,” she said. “They’re surviving when they might not have without an organ.”
HLA and bone marrow transplantation
The other part of the HLA lab focuses on bone marrow transplantation. Unlike solid organ transplantation, the process for a bone marrow transplant involves an attempt to reduce or completely wipe out a patient’s immune system via chemotherapy, followed by an infusion of stem cells to generate a new immune system. For a transplant to be successful, both immune systems must be closely matched. For many years, a patient’s best hope of finding a match was a sibling or unrelated donor from the Be The Match national bone marrow transplant registry—one of Versiti’s partners. But as the population has become more diverse, matching donors and recipients has become more complicated, requiring more sophisticated HLA typing.
“You need a much higher resolution of HLA genotyping in order to have a successful bone marrow transplant,” Dr. Schiller said. “In the early days of bone marrow transplantation, as testing methods evolved, our laboratory was one of the first to utilize Sanger sequence-based typing to match in clinical stem cell transplantation,” said Histocompatibility Technical Specialist Karen Pierce, BS, CHS(ABHI). Several decades later, Versiti Diagnostic Labs recognized that next-generation sequencing (NGS) would be the next game-changer, making it a more efficient and comprehensive approach to match donors and recipients.
“We led the field in transitioning to next-gen HLA sequencing in large part because we worked to help develop optimal test systems and analysis software to prove to ourselves that it works,” Dr. Schiller added. “When we launched in 2016, we were leading in the application of NGS technology for HLA. It has opened our eyes to what happens during the match process,” making it possible for more people to be considered donors and for patients to receive the transplants they need to survive.
Versiti Diagnostic Labs leading the charge
Versiti has long been on the cutting edge of technology to advance the diagnostic testing field. “We keep a focus on what technologies are available and work to develop new ones. The investment that Versiti is willing to make is what allows us to provide better outcomes for patients,” Dr. Schiller said. “It remains a focus in Versiti Diagnostic Labs to innovate. A strong innovation pipeline is what maintains our reputation as a thought leader in the HLA field in the eyes of our transplant partners.” Pierce added, “I’m proud of the fact that we have always been at the forefront, implementing new methodologies as they emerge. Sometimes, we even develop them ourselves. We have a rich history in terms of advancing the field and adding to it.”
Another thing that sets Versiti Diagnostic Labs apart is its ability to provide a full spectrum of support for solid organ and bone marrow transplant partners alike. “I’ve seen a lot of changes over time, but I think what is unique and has kept our laboratory at the forefront are the relationships and partnerships we’ve built over the years and continue to cultivate, especially with transplant programs,” Pierce said.
“There’s a big difference between sending tests to a big lab; they have no one to go to for advice and no one to help interpret a novel result. It’s difficult to get that level of support,” Dr. Schiller added. “The reason our lab is so successful is because everybody here is driven by the same goal: the patients we serve. Because of this, we’re successful in supporting these people when they need it.”
“When the need arises, we go out of our way to take care of patients,” she continued. “If a transplant patient needs day-of testing, we figure out how to do it. We’re problem solvers, and a lot of our solid organ and bone marrow transplant partners see us as an extension of their program. We go above and beyond consistently to help patients.”
As the HLA lab continues to grow and expand the number of programs it supports, Dr. Schiller recognizes the need to share information and train others to continue this lifesaving work. “The responsibility and reward of passing along knowledge to others is a major driver for everyone in our lab. Educating coordinators, fellows, blood bankers and new staff is a big responsibility within this community,” she said. “We make a difference in what we’re doing now, but we recognize that there needs to be a continuity of our knowledge and expertise to the next generation of scientists.”
“It’s a collaborative effort,” Pierce said. “We educate each other, we learn from each other and we have the desire to do the best that we can for the patients we serve.”
About the experts: Jennifer Schiller, PhD, D(ABHI), is the senior director of Histocompatibility & Immunogenetics at Versiti Diagnostic Labs. Karen Pierce, BS, CHS(ABHI), is the technical specialist for the Histocompatibility & Immunogenetics Lab.