{"id":"doi:10.1084/jem.20260506","kind":"article","title":"Epitope-diverse autoantibodies induce neutrophil-epithelial niches driving kidney injury in ANCA-associated glomerulonephritis","authors":["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"],"author_count":41,"year":2026,"published":"2026-10-19","venue":"The Journal of experimental medicine","cited_by":0,"doi":"10.1084/jem.20260506","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1084/jem.20260506","archive_url":"https://space-kitty.com/papers/doi:10.1084/jem.20260506","updated":null,"pmid":"42895484","pmcid":"PMC13679361","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC13679361/pdf","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_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Epitope-diverse autoantibodies induce neutrophil-epithelial niches driving kidney injury in ANCA-associated glomerulonephritis\" by Nishide M, Matsushita H, Mizuno Y et al., https://doi.org/10.1084/jem.20260506, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"single-cell-spatial","name":"Single-Cell & Spatial Omics","domain_slug":"biotech"}],"cited_in_dossiers":[]}