Targeting immune responses may save future organ transplants, according to an international study involving the University of Eastern Finland. The results were published in the prestigious Nature journal.
Researchers scrutinised the immune mechanisms behind the rejection of a pig kidney transplanted into a human. Based on the results, they were able to implement targeted medication to reverse the rejection.
For many of those in need of a kidney transplant, a suitable donor can’t be found at the right time. To boost the supply of available organs, experts are exploring the use of genetically modified pig kidneys. Genetic modifications are meant to keep the human immune system from recognising the animal organ as foreign and attacking it to cause rejection. However, recipients’ immune reactions can still lead to organ damage and failure after the surgery.
To better understand the immune mechanisms behind xenotransplant rejection, researchers at NYU Langone Health explored the transplantation of a genetically engineered pig kidney into a brain-dead recipient, whose family donated his body to science. For 61 days after the surgery, tissue, blood and body fluid samples were collected from the patient. As a result, the researchers were able to trace the network of interactions that occur among immune cells when a pig organ is being tolerated by a human and when it undergoes a rejection episode.
In the first of two recent reports, the study authors created a detailed map of both human and pig kidney immune activity in response to the transplant. They found that rejection was driven by antibodies – immune proteins that "tag" foreign substances for later destruction – as well as by T cells, which target and kill specific invaders. Once the researchers uncovered this set of reactions, they for the first time successfully reversed the rejection using a combination of drugs to temper both the antibody and T cell activity. There was no evidence of permanent damage or reduced kidney function after the intervention.
According to the researchers, the findings better prepare us for anticipating and addressing harmful immune reactions during pig-organ transplantation in living humans, setting the stage for more successful clinical trials in the near future.
The second report outlines immune activity in greater detail. The research team conducted a multi-omics analysis, which integrates information about gene function, gene expression (activity level) and proteins, as well as other data, to gain a holistic understanding of complex mechanisms at work in the immune system. A significant part of the bioinformatics analyses was performed by Eloi Schmauch, PhD, who graduated from the University of Eastern Finland last year and was active in the research groups of Professor Minna Kaikkonen-Määttä and University Researcher Suvi Linna-Kuosmanen.
The analysis revealed three major immune responses against the pig kidney: on postoperative day 21, driven by the human recipient's innate immune system that responds generally to intruders rather than to a specific target; on day 33, driven by human macrophage cells that engulf invaders; and on day 45, driven mostly by the human T cell response.
"Our multi-omics analysis uncovered various biomarkers that show promise as an early-warning system for pig organ rejection," Schmauch says.
In addition, the results may support the development of more targeted therapies to prevent transplant rejection.
NYU Langone Health press release
For further information, please contact:
Visiting Researcher Eloi Schmauch, University of Eastern Finland, A. I. Virtanen Institute for Molecular Sciences, https://uefconnect.uef.fi/en/eloi.schmauch/
Research articles:
Schmauch, E., Piening, B.D., Dowdell, A.K. et al. Multi-omics analysis of a pig-to-human decedent kidney xenotransplant. Nature (2025). https://doi.org/10.1038/s41586-025-09846-7
Montgomery, R.A., Stern, J.M., Fathi, F. et al. Physiology and immunology of pig-to-human decedent kidney xenotransplant. Nature (2025). https://doi.org/10.1038/s41586-025-09847-6
