《自然·医学》：猪肾移植免疫景观揭秘！世界首例分析发现，肾脏异种移植具有独特免疫景观，先天免疫激活是关键

Core Insights - Significant advancements have been made in xenotransplantation, with successful clinical cases reported for organs such as the heart, kidneys, liver, and lungs, particularly by research teams in China, raising hopes for the future of this field [1][8] - Although xenotransplantation is still in its early stages and long-term safety and efficacy remain unverified, successful implementation could effectively address organ shortages, providing new treatment options for thousands of patients awaiting transplants [8] Group 1: Research Findings - A recent paper published in Nature Medicine by a research team from Massachusetts General Hospital analyzed the immune landscape of the world's first patient receiving a pig kidney xenotransplant, revealing persistent activation of innate immunity despite immunosuppressive strategies [8] - The patient, a 62-year-old man with type 2 diabetes and hypertension, underwent surgery on March 16, 2024, after experiencing kidney failure following a previous transplant [4][11] - The pig kidney used for the xenotransplant was sourced from eGenesis, which edited 69 genes in the pig, including knocking out 59 endogenous retrovirus genes and introducing 7 human genes [4][11] Group 2: Immune Response Analysis - The patient exhibited an immune rejection response on the 8th day post-transplant, with immune profiling continuing until day 51, showing a significant decrease in adaptive immune cells while innate immune cells remained elevated [6][12] - The innate immune response was characterized by the activation of various pathways, particularly the NF-κB and IFN-I signaling axes, leading to sustained activation of monocytes/macrophages and increased production of multiple cytokines [12] - The study found that the level of donor-derived cell-free DNA (dd-cfDNA) surged approximately 1000 times during rejection, indicating graft damage, and suggested that dd-cfDNA could serve as a non-invasive biomarker for immune monitoring or therapeutic strategy development [7][12]