{
  "abstract": "Despite optimized immunosuppression, acute kidney transplant rejection affects 10-20% of recipients within the first year, and no reliable pre-transplant molecular test exists to identify patients at high risk, independent of the donor HLA matching. Across three independent cohorts of kidney transplant recipients, profiled by bulk RNA-sequencing with T-cell receptor repertoire analysis, flow cytometry, CyTOF with paired metabolomics, we identified a reproducible depletion of {gamma}{delta} T cells associated with rejection: an elevated {beta}/{gamma}{delta} T cell ratio in two post-transplant, biopsy-matched cohorts, and depletion of specific {gamma}{delta} T effector clusters in a third, longitudinally sampled cohort. In this third cohort, {gamma}{delta} T cell depletion was already present at the pre-transplant baseline in patients who subsequently developed rejection and remained detectable across the transplant course, indicating that it reflects recipient baseline immune biology rather than a consequence of graft injury. Longitudinal metabolomic profiling in this cohort identified time-dependent metabolic changes, including in amino acid metabolism that co-occur with the {gamma}{delta} signature and converge with it upon multi-omics integration. At the pre-transplant baseline, {gamma}{delta} T-cell marker expression alone showed exploratory discriminatory value for rejection risk (AUC = 0.69), improving marginally when integrated with metabolomic features (AUC = 0.71); larger prospective studies will be needed before clinical translation.",
  "abstract_shown": true,
  "affiliations": [
    "University of California, San Francisco"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "S. M. Kim"
    },
    {
      "name": "S. Sur"
    },
    {
      "name": "K. Koser"
    },
    {
      "name": "S. Pineda"
    },
    {
      "name": "O. Bestard"
    },
    {
      "name": "T. Koyama"
    },
    {
      "name": "T. Hoffmann"
    },
    {
      "name": "T. K. Sigdel"
    },
    {
      "name": "M. Sirota"
    },
    {
      "name": "J. Babdor"
    },
    {
      "name": "M. H. Spitzer"
    },
    {
      "affs": [
        0
      ],
      "name": "M. M. Sarwal"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6xgndfs2vnc3b.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.31.763223",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.31.763223v1.full",
  "id": "6xgndfs2vnc3b",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.31.763223v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.31.763223v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-31",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6xgndfs2vnc3b.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T12:21:11Z",
      "native_id": "10.64898/2026.10.31.763223",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.31.763223v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "A Reproducible Pre-Transplant γδ T-cell Effector Signature Reveals Immune-Metabolic Programs Associated with Kidney Allograft Rejection",
  "title_text": "A Reproducible Pre-Transplant γδ T-cell Effector Signature Reveals Immune-Metabolic Programs Associated with Kidney Allograft Rejection",
  "type": "preprint",
  "updated_at": "2026-11-05T00:20:38Z",
  "url": "https://research.draconitic.com/paper/6xgndfs2vnc3b",
  "venue": "bioRxiv",
  "versions": []
}