Single-cell RNA sequencing highlights the heterogeneity of neutrophils in granulomatosis with polyangiitis.
6 affiliations
- 1Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
- 2National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China.
- 3State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China.
- 4Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.
- 5School of Basic Medical Sciences, Tsinghua University, Beijing, China.
- 6Tsinghua Clinical Research Institute, School of Medicine, Tsinghua University, Beijing, China; School of Medicine and Vanke School of Public Health, Tsinghua University, Beijing, China.
Abstract
Background and objectives
Granulomatosis with polyangiitis (GPA), a clinical phenotype of anti-neutrophil cytoplasmic antibody-associated vasculitis, is characterized by necrotizing inflammation of blood vessels. While neutrophil dysregulation is central to its pathogenesis, its cellular heterogeneity and dynamic functional states remain poorly defined. To better understand the transcriptomic profile of neutrophils, we applied single-cell RNA sequencing (scRNA-seq) to peripheral blood samples from GPA patients and healthy controls (HCs).Methods
Peripheral blood samples were collected from three patients with active GPA and three HCs, followed by sequencing using the BD Rhapsody platform (Becton, Dickinson and Company). In a subsequent validation cohort, flow cytometry and quantitative real-time polymerase chain reaction were used to confirm specific neutrophil subtypes and explore their potential clinical significance.Results
Seven neutrophil clusters with distinct transcriptomic and functional profiles were identified. CXCL8-high and TXNIP-high subsets, predominant in HCs and GPA patients respectively, showed inflammatory profiles. CXCL8-high subsets also expressed immunoregulatory molecules to restrain inflammation. MMP8-high neutrophils showed enhanced antimicrobial activity, whereas IFIT1-high cells were linked to antiviral responses, suggesting that prior infections may contribute to anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) pathogenesis. PLA2G7-high neutrophils, identified as terminally differentiated by pseudotime analysis, were associated with disease relapse and renal involvement, indicating potential as AAV biomarkers. Transcriptional profiles of peripheral T and natural killer (NK) cells were also characterized, along with the analysis of systemic immune cell-cell communication networks.Conclusion
Our study enhances the understanding of the dynamic functional roles of neutrophils in GPA and may facilitate the development of therapeutic strategies aimed at selectively targeting disease-specific neutrophil subsets.
Related
- When Eosinophilic Granulomatosis With Polyangiitis (EGPA) Looks Like Granulomatosis With Polyangiitis (GPA): Navigating a Complex Case of Anti-neutrophil Cytoplasmic Antibodies (ANCA) Vasculitis
- Necrotizing Myositis as a Rare Presenting Manifestation of Childhood-Onset Granulomatosis With Polyangiitis: A Case Report.
- Prostatic Involvement in Granulomatosis with Polyangiitis: A Case Report and Scoping Review
- Isolated necrotizing scleritis revealing silent pulmonary granulomatosis with polyangiitis : A case report of rare diagnostic clue
- Rapidly Progressing Interstitial Fibrosis and Glomerulonephritis due to Granulomatosis With Polyangiitis Presenting With Calf Pain
BibTeX
@article{guo2026singlecell,
title = {{Single-cell RNA sequencing highlights the heterogeneity of neutrophils in granulomatosis with polyangiitis.}},
author = {Shuning Guo and Yangzhong Zhou and Dazhi Pang and Guanqiao Li and Yulin Lyu and Xinyuan Xu and Jing Li and Xinping Tian},
journal = {Rheumatology and immunology research},
year = {2026},
month = oct,
doi = {10.1515/rir-2026-0032},
url = {https://europepmc.org/article/MED/42924268},
note = {CC BY},
}
RIS
TY - JOUR
TI - Single-cell RNA sequencing highlights the heterogeneity of neutrophils in granulomatosis with polyangiitis.
AU - Shuning Guo
AU - Yangzhong Zhou
AU - Dazhi Pang
AU - Guanqiao Li
AU - Yulin Lyu
AU - Xinyuan Xu
AU - Jing Li
AU - Xinping Tian
PY - 2026
DA - 2026/10/22
JO - Rheumatology and immunology research
DO - 10.1515/rir-2026-0032
UR - https://europepmc.org/article/MED/42924268
AB - Background and objectives Granulomatosis with polyangiitis (GPA), a clinical phenotype of anti-neutrophil cytoplasmic antibody-associated vasculitis, is characterized by necrotizing inflammation of blood vessels. While neutrophil dysregulation is central to its pathogenesis, its cellular heterogeneity and dynamic functional states remain poorly defined. To better understand the transcriptomic profile of neutrophils, we applied single-cell RNA sequencing (scRNA-seq) to peripheral blood samples from GPA patients and healthy controls (HCs).Methods Peripheral blood samples were collected from three patients with active GPA and three HCs, followed by sequencing using the BD Rhapsody platform (Becton, Dickinson and Company). In a subsequent validation cohort, flow cytometry and quantitative real-time polymerase chain reaction were used to confirm specific neutrophil subtypes and explore their potential clinical significance.Results Seven neutrophil clusters with distinct transcriptomic and functional profiles were identified. CXCL8-high and TXNIP-high subsets, predominant in HCs and GPA patients respectively, showed inflammatory profiles. CXCL8-high subsets also expressed immunoregulatory molecules to restrain inflammation. MMP8-high neutrophils showed enhanced antimicrobial activity, whereas IFIT1-high cells were linked to antiviral responses, suggesting that prior infections may contribute to anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) pathogenesis. PLA2G7-high neutrophils, identified as terminally differentiated by pseudotime analysis, were associated with disease relapse and renal involvement, indicating potential as AAV biomarkers. Transcriptional profiles of peripheral T and natural killer (NK) cells were also characterized, along with the analysis of systemic immune cell-cell communication networks.Conclusion Our study enhances the understanding of the dynamic functional roles of neutrophils in GPA and may facilitate the development of therapeutic strategies aimed at selectively targeting disease-specific neutrophil subsets.
SN - 2719-4523
ER -