Immune profiling in a living human recipient of a gene-edited pig kidney
Nature Medicine. 2026;32(1):270-280. DOI 10.1038/s41591-025-04053-3. PMID 41507576. PMCID PMC12823403.
How to cite
AMA
Ribas GT, Cunha AF, Avila JP, Giarraputo A, Morena L, Lima K, et al. Immune profiling in a living human recipient of a gene-edited pig kidney. Nat Med. 2026;32(1):270-280. doi:10.1038/s41591-025-04053-3APA
Ribas, G. T., Cunha, A. F., Avila, J. P., Giarraputo, A., Morena, L., Lima, K., et al. (2026). Immune profiling in a living human recipient of a gene-edited pig kidney. Nature Medicine, 32(1), 270-280. https://doi.org/10.1038/s41591-025-04053-3BibTeX
@article{ribas2026immune,
title = {Immune profiling in a living human recipient of a gene-edited pig kidney},
author = {Ribas, G. T. and Cunha, A. F. and Avila, J. P. and Giarraputo, A. and Morena, L. and Lima, K. and others},
journal = {Nature Medicine},
volume = {32},
number = {1},
pages = {270--280},
year = {2026},
doi = {10.1038/s41591-025-04053-3},
pmid = {41507576}
}A gene-edited pig kidney was transplanted into a living person with end-stage kidney disease, and the question that followed was how the human immune system would respond to the new organ. Blood tests track the systemic response, but they cannot show what is happening inside the graft, cell by cell.
The team profiled the recipient with several methods and imaged frozen biopsies from the donor kidney and from the xenograft at two points after surgery. During an early rejection episode the tissue filled with T cells and macrophages; after treatment most of those subsets receded, while one macrophage population stayed. Reading which immune cells sat where, and when, turned a blood-level account into a picture of the graft itself.
Key findings
- Multiplexed imaging mapped immune cells in the graft tissue. Frozen biopsies from the day-0 donor kidney and the xenograft at days 8 and 34 were stained for glomerular and tubular markers (podocin, β-catenin), leukocytes (CD45), endothelium (CD31), T cells (CD4, CD8), macrophages (CD68, CD163) and NK cells (NKG2A), then counted cell by cell across each whole-slide section.
- Rejection filled the graft with T cells and macrophages. On post-transplant day 8, the rejecting xenograft showed increased CD4+ and CD8+ T cells, CD68+ and CD163+ macrophages, and NK cells, with CD4+ T cells and CD68+ macrophages the most prominently increased subsets.
- After treatment, one macrophage population persisted. By day 34, T cells, M1 (CD68+) macrophages and NK cells had declined, while M2 (CD163+) macrophages stayed elevated; human-specific HLA class I staining showed most macrophages in the graft were human rather than donor cells.
Orion in the methods
“After a surfactant wash and enhancer treatment, slides were incubated overnight at 4 °C with ArgoFluor‑conjugated antibodies and Hoechst 33342. The next day, slides were washed extensively in PBS, mounted in ArgoFluor mounting medium (RareCyte 42‑1214‑000), and imaged on an Orion microscope.”
— Ribas et al., Nature Medicine (2026), Methods, “Multiplex immunofluorescence”
Why it matters for Orion users
If you are weighing Orion for a tissue study, look at what its spatial arm was asked to carry here. The core question was where immune cells sat inside a transplanted organ, and how that picture changed as the graft was rejected and then treated. You cannot answer that from blood, and you cannot answer it from a dissociated sample that discards position. It needs single-cell measurements read in place, across a whole biopsy section, in enough markers to separate CD4 and CD8 T cells, two macrophage states, NK cells and the tissue's own structure at once. The same panel also carried a human-specific HLA class I marker, so each cell could be assigned not only a lineage but a species of origin, which is how the authors showed most graft macrophages were human rather than donor. The biopsies were small and irreplaceable, so imaging the intact section rather than dissociating it mattered. The authors then ran the images through MCMICRO, an open segmentation and quantification pipeline, keeping the analysis theirs to choose.
