# Epitope-diverse autoantibodies induce neutrophil-epithelial niches driving kidney injury in ANCA-associated glomerulonephritis

Article · Nishide M, Matsushita H, Mizuno Y, Nishimura K, Lelliott PM, Kawada S, Fujii T, Kamikawaji S, Nonaka T, Motooka D, Metsugi S, Shimagami H, Miyamoto AT, Kato Y, Tsujimoto K, Edahiro R, Shirai Y, Yamamoto Y, Naito Y, Konaka H, Izumi M, Naito M, Nakanishi Y, Namba-Hamano T, Inoue K and 16 more

- Archive id: doi:10.1084/jem.20260506
- Published: 2026-10-19
- Venue: The Journal of experimental medicine
- DOI: https://doi.org/10.1084/jem.20260506
- PMID: 42895484
- PMCID: PMC13679361
- Citations: 0
- Source URL: https://doi.org/10.1084/jem.20260506
- PDF: https://europepmc.org/articles/PMC13679361/pdf
- Provenance: europepmc

## 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 reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Single-Cell & Spatial Omics](https://space-kitty.com/topics/single-cell-spatial)

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