May 29, 2024

When it comes to kidney transplants, compatibility between the donor and recipient is a critical factor for success. However, even when a donor and recipient are closely matched, long-term drug therapy is often necessary to suppress the recipient’s immune system and prevent the rejection of the transplanted organ. But what if there was a way to increase compatibility, reducing the need for lifelong anti-rejection medications? 


Researchers at the University of Wisconsin–Madison and Stanford University developed a groundbreaking approach that may revolutionize kidney transplants, allowing for greater compatibility between donors and recipients and potentially eliminating the need for immunosuppressant drugs. This method, tested in a nonhuman primate model, creates a dual immune system with the recipient and offers hope to kidney transplant patients, even when they are less closely matched to their donors. 


The Journey to Compatibility 

Led by Dixon Kaufman, a Professor of Surgery at UW–Madison and Director of the UW Health Transplant Center, the research team aimed to maintain kidney function without rejection in a monkey model that closely resembled human transplants. They also sought to prevent graft-versus-host disease, a complication when the donor’s immune cells attack the new host. 


According to the recent study published in Transplant International, the team worked with 11 monkeys from the Wisconsin National Primate Research Center. These monkeys had less tissue type matching than what had previously been attempted in human donor-recipient pairs. 


The major histocompatibility antigens, two key strings of tissue typing proteins found on the surface of cells, play a pivotal role in the immune system’s ability to recognize “self” and “non-self.” The monkeys in this tolerance induction study had just one match among these key protein strings, while successful human transplant pairings previously required two matches. 


The Innovative Procedure 

After receiving donor kidneys, the monkeys underwent a procedure involving thin beams of radiation, targeting key parts of their immune systems, temporarily suppressing them, and an infusion of blood and immune cells from their kidney donors. The goal was to create a mixed chimeric state in the recipients, where their immune system was a combination of two animals: part donor and part recipient.  


All animals in the study were gradually weaned off immunosuppressant drugs, and two monkeys maintained chimeric immune systems. These two animals remained healthy with normal kidney function for more than four years without experiencing rejection or graft-versus-host disease or needing drugs to suppress their immune systems. 


Dixon Kaufman noted, “This is the longest duration of tolerance induction reported in this kind of animal model. Although more challenging compared to identically matched pairs, this protocol shows it is feasible to achieve long-term tolerance between more distantly related pairs with tissue incompatibility.” 


A Brighter Future for Transplants 

Kaufman believes the knowledge gained through this research could have far-reaching implications for various donor transplants, including those from deceased donors who may be even more distantly related. As advancements continue, the hope for improved compatibility between donors and recipients becomes increasingly promising. 

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