Challenges in pig-to-human kidney xenotransplantation

Alexandre Loupy and colleagues1Loupy A Goutaudier V Giarraputo A et al.Immune response after pig-to-human kidney xenotransplantation: a multimodal phenotyping study.Lancet. 2023; 402: 1158-1169Summary Full Text Full Text PDF PubMed Google Scholar reported an exciting breakthrough in porcine kidney xenotransplantation into human recipients. The results in figures 3 and 4 have drawn our attention. The authors observed increased expression of multiple HLA genes by next-generation sequencing. Since the xenografts before implantation (the control group in figure 3A) were taken directly from pigs and had not been perfused with human blood, they are expected to express swine leukocyte antigen (SLA), not HLA. The possibility of cross-reaction between different species is slim because the number of SLA-expressing cells (pig kidney) substantially outweighs any trace of human cells in the transplanted kidney (the experimental group in figure 3A). Because the volcano plots of differentially expressed genes in figures 3 and 4 are presented as fold changes, we wonder how the fold changes were calculated if the numbers used for comparison are zero (human genes are not detectable in the control group). We declare no competing interests. Immune response after pig-to-human kidney xenotransplantation: a multimodal phenotyping studyDespite favourable short-term outcomes and absence of hyperacute injuries, our findings suggest that antibody-mediated rejection in pig-to-human kidney xenografts might be occurring. Our results suggest specific therapeutic targets towards the humoral arm of rejection to improve xenotransplantation results. Full-Text PDF Challenges in pig-to-human kidney xenotransplantation – Authors' replyThe Correspondence from Liming Cheng and Kai Liu on our Article1 contains several comments that deserve further discussion. The decision to use thymokidneys from pigs with only the alpha-1, 3-galactosyltransferase antigen knocked out (Gal-KO) was made for several reasons.2 First, this herd is being successfully bred, making it easy to rapidly produce Gal-KO pigs at the large scale that is needed if xenotransplantation is to effectively address the shortage of organs for human transplantation. To consistently breed pigs with a substantial number of genetic edits is currently challenging. Full-Text PDF