{
  "abstract": "Autoantibody-mediated inflammation drives tissue injury in autoimmune diseases, yet how pathogenic antibodies evoke local immune activation remains poorly understood. Here, we show that spatially organized neutrophil-epithelial niches contribute to kidney injury in myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody-associated glomerulonephritis. Single-cell-resolved spatial transcriptomics of treatment-naïve patient kidney biopsies identified early-phase inflammatory niches enriched with HAVCR1+ injured proximal tubular epithelial cells, neutrophils, lymphocytes, and TREM2+ macrophages. Injured epithelial cells expressed chemokines including CXCL6 and CXCL16, defining a microenvironment associated with local immune cell accumulation. Neutrophils within these niches were characterized by transcriptional programs enriched for type II interferon and Fcγ receptor (FcγR)-related signaling. Mechanistically, combinations of monoclonal anti-MPO antibodies recognizing distinct epitopes enhanced neutrophil activation and induced pauci-immune crescentic glomerulonephritis in mice, recapitulating key aspects of epithelial injury observed in human kidneys. One-armed anti-MPO antibodies engineered to minimize FcγR engagement ameliorated kidney injury in mice. Together, these findings identify pathogenic neutrophil-epithelial niche formation as a driver of autoimmune kidney injury.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, The University of Osaka, Suita, Osaka, Japan.",
    "Department of Immunopathology, World Premier International Research Center Initiative (WPI), Immunology Frontier Research Center (IFReC), The University of Osaka, Suita, Osaka, Japan.",
    "Department of Advanced Clinical and Translational Immunology, Graduate School of Medicine, The University of Osaka, Suita, Osaka, Japan.",
    "Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.",
    "Joint Research Chair of Innovative Drug Discovery in Immunology, World Premier International Research Center Initiative (WPI), Immunology Frontier Research Center (IFReC), The University of Osaka , Suita, Osaka, Japan.",
    "Biophotonics Laboratory, World Premier International Research Center Initiative (WPI), Immunology Frontier Research Center (IFReC), The University of Osaka, Suita, Osaka, Japan.",
    "NGS Core Facility, Bioinformatics Center, Research Institute for Microbial Diseases, The University of Osaka, Suita, Osaka, Japan.",
    "Department of Statistical Genetics, Graduate School of Medicine, The University of Osaka, Suita, Osaka, Japan.",
    "Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.",
    "Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), The University of Osaka, Suita, Osaka, Japan.",
    "Department of Nephrology, Graduate School of Medicine, The University of Osaka, Suita, Osaka, Japan.",
    "Department of Urology, Graduate School of Medicine, The University of Osaka, Suita, Osaka, Japan.",
    "Itami City Hospital , Itami, Japan.",
    "Department of Statistical Immunology, World Premier International Research Center Initiative (WPI), Immunology Frontier Research Center (IFReC), The University of Osaka, Suita, Osaka, Japan.",
    "Department of Genome Informatics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.",
    "Japan Agency for Medical Research and Development - Core Research for Evolutional Science and Technology (AMED-CREST), The University of Osaka , Suita, Osaka, Japan.",
    "Center for Infectious Diseases for Education and Research (CiDER), The University of Osaka , Suita, Osaka, Japan.",
    "Center for Advanced Modalities and DDS (CAMaD), The University of Osaka , Suita, Osaka, Japan."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 41,
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      "name": "Tomoko Namba-Hamano",
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      "name": "Kazunori Inoue",
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      "name": "Atsushi Takahashi",
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      "name": "Masayuki Mizui",
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      "name": "Shigeaki Nakazawa",
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      "name": "Yoichi Kakuta",
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      "name": "Kenji Funakoshi",
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      "name": "Makoto Terada",
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      "name": "Machiko Irie",
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      "name": "Takuya Torizawa",
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      "name": "Ryusuke Omiya",
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      "name": "Nicolas I Smith",
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      "name": "Yoshitaka Isaka",
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      "name": "Atsushi Kumanogoh",
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  "bibtex": "https://research.draconitic.com/paper/089fjmc2pn2t8.bib",
  "cited_by": 1,
  "doi": "10.1084/jem.20260506",
  "fulltext_url": "https://europepmc.org/articles/PMC13679361",
  "id": "089fjmc2pn2t8",
  "issns": [
    "0022-1007",
    "1540-9538"
  ],
  "landing_url": "https://europepmc.org/article/MED/42895484",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2740|Vasculitis and related conditions"
    ]
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  "openalex": "W7222987862",
  "pdf_url": "https://europepmc.org/articles/PMC13679361?pdf=render",
  "pmcid": "PMC13679361",
  "pmid": "42895484",
  "published": "2026-10-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/089fjmc2pn2t8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:32Z",
      "native_id": "MED:42895484",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42895484"
    }
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  "subjects": [
    {
      "field": "biology",
      "origin": "journal-openalex:2403|T-cell and B-cell Immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Epitope-diverse autoantibodies induce neutrophil-epithelial niches driving kidney injury in ANCA-associated glomerulonephritis.",
  "title_text": "Epitope-diverse autoantibodies induce neutrophil-epithelial niches driving kidney injury in ANCA-associated glomerulonephritis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:32Z",
  "url": "https://research.draconitic.com/paper/089fjmc2pn2t8",
  "venue": "The Journal of experimental medicine",
  "versions": []
}