{
  "abstract": "Background: Antibody-mediated rejection remains the leading cause of kidney allograft failure in pediatric recipients. While non-HLA antibodies targeting G protein-coupled receptors, particularly anti-endothelin-1 type A receptor (ETAR) antibodies, have been implicated in allograft injury, their functional activity and independent pathogenic role in pediatric kidney transplantation remain poorly characterized.\n\nMethods: In this study involving 46 pediatric kidney transplant recipients, anti-ETAR antibodies were quantified and their functional activity assessed using a β-arrestin–based luminometric bioassay in ETAR-transfected CHO cells. Furthermore, IgG-induced migration of T-lymphocytes and NK-92 cells was evaluated by chemotaxis assay. Renal function was monitored longitudinally. Predictive models of eGFR decline between consecutive follow-up visits were developed using restricted cubic spline regression with bootstrap validation.\n\nResults: Patient-derived IgG exhibited concentration-dependent agonistic activity on ETAR, including samples with anti-ETAR IgG below the standard positivity threshold (17 U/mL). Moreover, IgG enhanced endothelin-1–induced receptor activation, independently of anti-ETAR antibody levels. IgG from pediatric transplant recipients with elevated anti-ETAR levels significantly increased T-lymphocyte and NK-92 cell migration, irrespective of the presence of anti-HLA antibodies. Anti-ETAR IgG levels were associated with immune cell migration and with the decline in eGFR (Spearman ρ = 0.52). In multivariable modeling, however, antibody concentration retained no validated predictive information after bootstrap optimism correction, whereas IgG-induced T-cell migration remained associated with eGFR decline after adjustment for time since transplantation and for HLA donor-specific antibodies (DSA).\n\nConclusion: In pediatric kidney transplant recipients, anti-ETAR antibodies are functionally active irrespective of their levels, promoting receptor signaling and immune cell recruitment associated with graft function deterioration. These results suggest that functional assessment, particularly T-cell migration, may provide complementary information beyond antibody concentration and warrants further investigation as a potential approach to risk stratification.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova",
    "Transplant Immunology Laboratory, Institute of Pediatric Research “Città della Speranza”",
    "Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova",
    "Laboratory of Immunopathology and Molecular Biology of the Kidney, Department of Women’s and Children’s Health, University of Padova",
    "Institute of Pediatric Research Città della Speranza",
    "Pediatric Nephrology, Department of Women’s and Children’s Health, Padova University Hospital",
    "Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova",
    "Transplant Immunology Unit, Padova University Hospital"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Marta Vadori"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ezgi Demirkilic"
    },
    {
      "affs": [
        2
      ],
      "name": "Corrado Lanera"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Benedetta Antoniello"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Susanna Negrisolo"
    },
    {
      "affs": [
        5
      ],
      "name": "Emanuele Vianello"
    },
    {
      "affs": [
        6
      ],
      "name": "Caterina Di Bella"
    },
    {
      "affs": [
        3,
        4,
        5
      ],
      "name": "Elisa Benetti"
    },
    {
      "affs": [
        0,
        1,
        7
      ],
      "name": "Emanuele Cozzi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fk66y36gpmjkc.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1925567",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13735602/",
  "id": "fk66y36gpmjkc",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1925567/full",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2747|Renal Transplantation Outcomes and Treatments"
    ]
  ],
  "openalex": "W7223174177",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1925567/pdf",
  "pmcid": "PMC13735602",
  "pmid": "42991295",
  "published": "2026-10-22",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/fk66y36gpmjkc.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1925567",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1925567/full"
    },
    {
      "first_seen": "2026-11-09T12:21:15Z",
      "native_id": "PMC13735602",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fimmu.2026.1925567"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2747|Renal Transplantation Outcomes and Treatments",
      "subfield": "surgery"
    }
  ],
  "title": "Functional activity of anti-endothelin type A receptor antibodies as a predictive tool of allograft injury in pediatric kidney transplantation",
  "title_text": "Functional activity of anti-endothelin type A receptor antibodies as a predictive tool of allograft injury in pediatric kidney transplantation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:15Z",
  "url": "https://research.draconitic.com/paper/fk66y36gpmjkc",
  "venue": "Frontiers in Immunology",
  "versions": []
}