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

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.

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Publication Details

Journal
Nature Communications
Published
2025-04-24
DOI
https://doi.org/10.1038/s41467-025-58550-7
Citations
9
Primary Topic
Vasculitis and related conditions
Type
article
Field-Weighted Citation Impact
13.67

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article

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

Yuji Yamamoto, Kohei Tsujimoto, Kunihiro Hattori, Ryusuke Omiya et al.
9 citations
Nature Communications
Vasculitis and related conditions
13.67
article

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

Yuji Yamamoto, Kohei Tsujimoto, Kunihiro Hattori, Ryusuke Omiya, S. Kawada, Shoichi Metsugi, Atsushi Kumanogoh, Masayuki Nishide, Yukinori Okada, Masashi Narazaki, Hiroshi Shimagami, Ryuya Edahiro, Eri Itotagawa, Kazuki Matsukawa, Maiko Naito, Yuya Shirai, Yasuhiro Kato, Kei Nishimura, Hiroaki Matsushita, Takahiro Kawasaki
article en
9 citations

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.

Nature CommunicationsVol. 16(1)
Japan Agency for Medical Research and Development (JP), RIKEN Center for Integrative Medical Sciences (JP), Osaka International University (JP), The University of Tokyo (JP), The University of Osaka (JP)
Japan Agency for Medical Research and Development, Ono Pharmaceutical, Japan Society for the Promotion of Science, Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Moonshot Research and Development Program
Openalex Percentile: Top 1%
Vasculitis and related conditions
13.67
DOIOpen Access PDFOpenAlex
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