Viral and pharmacogenomic testing help clinicians detect infection early, tailor immunosuppression, and improve long-term outcomes for organ transplant recipients.
In 2024, over 48,000 organ transplants were performed in the U.S. alone, averaging 123 transplants per day. Mayo Clinic performs nearly twice as many solid-organ transplants as any other center in the United States. Once a patient receives a donor organ (heart, kidney, liver, pancreas, or lung), their journey is far from over. Patients must be carefully tested and monitored for viral infections and specific genetic variants that could complicate or hasten organ rejection. To support this, Mayo Clinic Laboratories offers a comprehensive test menu that provides both pre- and post-transplant testing needs.
“Within infectious diseases, we're able to cover the significant concerns for viral and bacterial infections,” says David Grunst, a product manager specializing in infectious disease tests at Mayo Clinic Laboratories. “We're able to address each phase of the patient's recovery, pre- and post-transplant.”
Addressing vulnerability to infection well after surgery
Organ transplant recipients, because of their compromised immune systems, are more vulnerable to infections, which can even come through donor blood products. An infection may also come from the donor organ itself.
“That’s why, after the transplant, every recipient has to be re-screened,” says Joseph Yao, M.D., director of Mayo Clinic’s Virology Laboratory in the Division of Clinical Microbiology. “Because the patient may acquire the infection from the transplanted organ, even though the organ donor was negative when initially screened. But it could be falsely negative because the testing of the donor is too close to the time of their exposure, so it didn't give the test a chance to become positive before organ retrieval.”
Further, a patient’s vulnerability to infection continues well after they’re released from the hospital.
“We're not only considering possible infections from the transplanted organ, or hospital-acquired infections, but also after the patient has gone back to their day-to-day life,” says Grunst. “They're going back into their communities and may come across various opportunistic infections, pathogens like CMV (cytomegalovirus) and EBV (Epstein Barr virus), and molds like Aspergillus. And due to the compromised state of the immune system, these patients may be more likely than individuals like you and me to acquire such infections. So it's critical their care team be well-educated and test for these infections as the patient recovers after organ transplant.”
Because Mayo has such a large transplant patient population, the care team is able to support them with a high level of clinical and laboratory expertise. “The patient will present back to their care team with symptoms, and it's up to that care team to recognize those symptoms and consider something like an adenovirus infection and order the appropriate testing,” says Grunst.
“We're not only considering possible infections from the transplanted organ, or hospital-acquired infections, but also after the patient has gone back to their day-to-day life,” says Grunst.
Adenovirus (ADV) is a common infection that causes mild cold or flu-like symptoms. “In healthy adults or children, they generally get over it, but it doesn't prevent them from getting future reinfection,” says Dr. Yao. “So having an infection with adenovirus, unlike some of our other viral infections, does not confer immunity to future infection with this virus. When these transplant patients become immunocompromised in the future, they may get exposed to and contract adenovirus again, and they may develop severe disease and can die from the disseminated infection.”
This is why testing for adenovirus is so important for these patients. To that end, Mayo Clinic Laboratories recently launched a test (Mayo ID: ADVQU) to detect and quantify adenovirus in human plasma.
“We use this test to see if an at-risk organ or stem cell transplant recipient presenting with fever has adenoviral viremia or disseminated disease due to this virus,” says Dr. Yao. “We also use it to monitor infection progression in such individuals with or without antiviral treatment. The challenge to transplant clinicians is when to know or determine what level of adenovirus DNA is clinically significant to indicate the presence of disseminated disease that necessitates therapeutic intervention.”
Promoting standardized testing amid no consensus
In other words, there is no consensus as to how much viral load in a patient’s blood plasma determines clinical significance, versus a viral level that may not have any clinical significance. Each institution must set up its own threshold for such viral load. In addition, different testing labs report out different units of measurements that are not standardized across the labs. Why? There is yet no regulatory requirement for the performing lab to switch from old units of measurement to newer, standardized ones. And these units of measurement continue to evolve.
“There’s always a transition period when we have to help guide our clinicians and laboratory clients, who are used to the older way of interpreting test results, to pursue the newer way, for better care of these transplant patients,” says Dr. Yao. “All, except two (Mayo IDs: QHV6C and QHV6P) of our viral load assays are calibrated to WHO standards, called ‘international standards.’ We want to take the lead in promoting assays that will be universally applicable regardless of which lab is generating the result. If we use a standardized unit of measurement, patients can go from one lab to another without posing problems to the clinicians and to the patient in interpreting the test results. That's the way we should go.”
This is especially important to transplant patients, as such testing continues “until a negative result is achieved,” says Grunst.
Pharmacogenomic testing
"We want to take the lead in promoting assays that will be universally applicable regardless of which lab is generating the result."
In addition, every transplant patient has a different tolerance, or genetic response, to immunosuppressants — medications that keep the body’s immune system from “attacking” the transplanted organ. This is where pharmacogenomic testing comes in, particularly a comprehensive genetic test (Mayo ID: 3A5Q). Developed by Mayo Clinic, the test covers five genetic variants within the CYP3A5 gene. The CYP3A5 enzyme, which is primarily expressed in the liver, is responsible for metabolizing a number of drugs, including tacrolimus, a core immunosuppressant in post-transplant care. Each CYP3A5 variant means a patient’s metabolism of tacrolimus will be reduced; thus, the test results guide clinicians on doses of this drug to increase its effectiveness while mitigating toxic side effects.
“What sets our tests apart from other labs is, a lot of labs will only test for the CYP3A5*3 variant, and we actually test for five variants,” says Ann Moyer, M.D., Ph.D., a consultant in Mayo Clinic’s Laboratory of Genetics and Genomics.
The 3A5Q test focuses on a single gene, CYP3A5 (and its multiple variants), relevant to the transplant population. This gene is also included as part of a larger panel (Mayo ID: PGXQP) that tests multiple genes. “The focused panel covers gene-drug pairs with a really high level of evidence for general use,” says Dr. Moyer. “They get CYP3A5, but then they get multiple other genes that we think are important for pharmacogenomics too.”
Having the focused panel done pre-transplant can help establish a baseline for treatment.
Dr. Moyer continues, “If the patient gets this focused panel or just pharmacogenomic testing in general, that can cover a lot of different indications and a lot of different medications that the patient could be on or will take in the future. So if they could get that panel testing before their transplant and it already had CYP3A5 on it, then, when they go on to get their transplant, they already have that information. They're ready to go on day one and can maybe be started at a different tacrolimus dose if needed, instead of having to wait for the therapeutic drug monitoring for initial dose adjustments.”
An individualized approach to immunosuppressant dosing
Another area that underscores Mayo’s depth of expertise is when the pharmacogenomic pharmacists work closely with clinicians, and often with patients, to determine appropriate immunosuppressant treatments using an individualized approach.
John Logan Black, M.D., is a consultant in Mayo Clinic’s Division of Laboratory Genetics and Genomics. “The patient is typically going to be on a host of new medications after they've had the transplant done, because you're preventing rejection,” he says. “There may be some complications or maybe an infection. There are so many things that can happen. So, our pharmacists are really good at helping the clinician, and therefore the patient, determine medications and doses, what should be avoided and what is not an issue.”
Another important immunosuppressant drug is azathioprine, a class of thiopurine drugs that the lab also supports via a Mayo-developed panel (Mayo ID: TPNUQ) that includes two genes, TPMT and NUDT15. Both genes encode enzymes that metabolize thiopurines.
“This is the test we would recommend for patients who will be prescribed a thiopurine so that clinicians can, again, make sure that they're on the correct dose,” says Dr. Moyer. “In that case, the biggest concern is actually toxicity, because patients that have deficiency of TPMT or a deficiency of NUDT15, when you give them the full dose of azathioprine, they won't metabolize enough of it to an inactive metabolite.”
Immunosuppressive therapy tailored to each patient’s evolving risk profile
Mayo Clinic Laboratories offers precision-driven solutions that combine pharmacogenomics (genetic testing to guide initial tacrolimus dosing in non-liver transplants); therapeutic drug monitoring to help reduce the risk of transplant rejection for all transplant types; expert clinical support, including geneticists, transplant pharmacists, and pathologists; and decades of transplant leadership. All testing is supported by clinical trials, translational studies on antibody-mediated rejection, and multidisciplinary care.
Test panels never stop evolving, improving
Mayo Clinic Laboratories’ comprehensive transplant test menu is ever-evolving, always leaning into a future that’s based on a long history of designing these panels.
“Back in the day, and we're talking a long time ago now, we were the first to come out with a panel of several genes,” says Dr. Black. “So we've been doing panels before anybody was doing panels, and we just keep changing them to make them better and better for the patient. This is a really active field, so as a new drug, gene pair, or a new variant in a gene becomes important, we'll add it, and therefore our panels change a little bit over time.”
Of course, there’s the human element of collaboration that’s also critical to Mayo remaining a leader in this field.
“Pharmacogenomic pharmacists have been around for a long time at Mayo Clinic, and they are very much a partner with us in the lab,” says Dr. Moyer, “They're the ones that are doing a lot of counseling, not only about the pharmacogenomic interaction with a drug, but they also think about drug-drug interactions and a more holistic approach to optimizing medication therapy for the patient. We all bring different pieces of expertise to the table and, by working together, we can deliver the best patient care.”
"So we've been doing panels before anybody was doing panels, and we just keep changing them to make them better and better for the patient."
