“In two papers published in Nature today, researchers describe the main factors that cause the human immune system to reject transplanted organs. Researchers say the findings will improve outcomes for living people who receive organs from other people, or from animals…

The latest pig-organ transplant was performed on 14 July 2023 at New York University Langone in New York City. The kidney and thymus were taken from a pig supplied by Revivicor, a subsidiary of biotechnology firm United Therapeutics, based in Virginia. The pigs had a single genetic modification, removing gene GGAT1, to stop the production of a sugar called alpha-gal on cells. Alpha-gal has been found to cause organ rejection in transplant surgeries in non-human primates.

Immediately after the transplant, the kidney appeared healthy and produced urine. But 33 days after the procedure, the kidney’s function suddenly declined, and a biopsy showed that the organ was being rejected and damaged by antibodies. The team replaced the person’s plasma and gave them steroids and a drug called pegcetacoplan, which stopped pig cells being tagged for destruction by the immune system. But on day 49, another biopsy showed a different type of rejection, in which inflammatory cells had infiltrated the kidney’s surface. This was treated with an immunosuppressant that destroys T cells and stopped the organ from being rejected. Kidney function was also fully restored. The research team chose to end the experiment at 61 days.

Following the transplant, the team also analysed the person’s blood to map how the immune system responded on a molecular level. They showed that the pig kidney increasingly expressed genes associated with rejection, such as CXCL9, CXCL10 and CXCL11, and their expression decreased after the rejection was stopped. High levels of macrophages and natural killer cells, a type of T cell, which are part of the innate immune system, were observed on day 33. Mohiuddin says this suggests that T cells play a more prominent role in rejection than was previously thought.”

From Nature.