Neutrophil single-cell analysis identifies a type II interferon-related subset for predicting relapse of autoimmune small vessel vasculitis

Masayuki Nishide (), Kei Nishimura, Hiroaki Matsushita, Shoji Kawada, Hiroshi Shimagami, Shoichi Metsugi, Yasuhiro Kato, Takahiro Kawasaki, Kohei Tsujimoto, Ryuya Edahiro, Yuya Shirai, Eri Itotagawa, Maiko Naito, Yuji Yamamoto, Kazuki Matsukawa, Ryusuke Omiya, Yukinori Okada, Kunihiro Hattori, Masashi Narazaki and Atsushi Kumanogoh ()
Additional contact information
Masayuki Nishide: Osaka University
Kei Nishimura: Osaka University
Hiroaki Matsushita: Osaka University
Shoji Kawada: Osaka University
Hiroshi Shimagami: Osaka University
Shoichi Metsugi: Osaka University
Yasuhiro Kato: Osaka University
Takahiro Kawasaki: Osaka University
Kohei Tsujimoto: Osaka University
Ryuya Edahiro: Osaka University
Yuya Shirai: Osaka University
Eri Itotagawa: Osaka University
Maiko Naito: Osaka University
Yuji Yamamoto: Osaka University
Kazuki Matsukawa: Osaka University
Ryusuke Omiya: Osaka University
Yukinori Okada: Osaka University
Kunihiro Hattori: Osaka University
Masashi Narazaki: Osaka University
Atsushi Kumanogoh: Osaka University

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract To identify the dynamics of neutrophil autoimmunity, here we focus on anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and perform single-cell transcriptome and surface proteome analyses on peripheral white blood cells from patients with new-onset microscopic polyangiitis (MPA). Compared with controls, two neutrophil populations, immature neutrophils and neutrophils with type II interferon signature genes (Neu_T2ISG), are increased in patients with MPA. Trajectory and cell–cell interaction analyses identify Neu_T2ISG as a subset that differentiates from mature neutrophils upon stimulation with IFN-γ and TNF, which synergize to induce myeloperoxidase and Fcγ receptors expression on the neutrophil cell surface and promote ANCA–induced neutrophil extracellular trap formation. Case-by-case analysis indicates that patients with a high proportion of the Neu_T2ISG subset are associated with persistent vasculitis symptoms. A larger cohort analysis shows that serum IFN-γ levels at disease onset correlate with susceptibility to disease relapse. Our findings thus identify neutrophil diversity at the single cell level and implicate a biomarker for predicting relapse in small vessel vasculitis.

Date: 2025
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DOI: 10.1038/s41467-025-58550-7

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