21RT

Cryo-EM structure of mouse myeloperoxidase in complex with Fab fragments of antibodies mAb-A46 and mAb-B88

Summary for 21RT

• Entry DOI: 10.2210/pdb21rt/pdb
• EMDB information: 67951
• Descriptor: mAb-A46 Fab Heavy chain, mAb-A46 Fab Light chain, mAb-B88 Fab Heavy chain, ... (9 entities in total)
• Functional Keywords: myeloperoxidase, immune system
• Biological source: Mus musculus; More
• Total number of polymer chains: 6
• Total formula weight: 164247.72

Authors

Fujii, T.,Irie, M.,Torizawa, T. (deposition date: 2025-12-23, release date: 2026-09-16, Last modification date: 2026-11-04)

Primary citation

Nishide, M.,Matsushita, H.,Mizuno, Y.,Nishimura, K.,Lelliott, P.M.,Kawada, S.,Fujii, T.,Kamikawaji, S.,Nonaka, T.,Motooka, D.,Metsugi, S.,Shimagami, H.,Miyamoto, A.T.,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.,Takahashi, A.,Mizui, M.,Nakazawa, S.,Kakuta, Y.,Funakoshi, K.,Terada, M.,Irie, M.,Torizawa, T.,Omiya, R.,Smith, N.I.,Isaka, Y.,Nonomura, N.,Okada, Y.,Hattori, K.,Narazaki, M.,Kumanogoh, A.
Epitope-diverse autoantibodies induce neutrophil-epithelial niches driving kidney injury in ANCA-associated glomerulonephritis.
J.Exp.Med., 223:-, 2026

PubMed 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.

PubMed: 42895484
DOI: 10.1084/jem.20260506

Experimental method

ELECTRON MICROSCOPY (2.95 Å)