Deep Immunophenotyping Unravels the Double Negative T cells and PD-1-Mediated Inflammatory Exhaustion in Ankylosing Spondylitis.
6 affiliations
- 1State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, and Human Phenome Institute, Fudan University, Shanghai, 200438 China.
- 2Department of Rheumatology and Immunology, Taixing People's Hospital, 98 Runtai South Road, Taixing, 225400 Jiangsu China.
- 3Research Unit of Dissecting the Population Genetics and Developing New Technologies for Treatment and Prevention of Skin Phenotypes and Dermatological Diseases (2019RU058), Chinese Academy of Medical Sciences, Shanghai, 200438 China.
- 4Department of Rheumatology, Institute of Rheumatology, Immunology and Allergy, Huashan Hospital, Fudan University, Shanghai, 200040 China.
- 5Fudan University Taizhou Institute of Health Sciences, Taizhou, 225326 China.
- 6Institute of Immunophenome, Human Phenome Institutes (Shanghai), Shanghai, 201203 China.
Abstract
Ankylosing spondylitis (AS) is a chronic, immune-mediated inflammatory disorder primarily affecting the axial skeleton. It is characterized by bony fusion and syndesmophyte formation of the spine, leading to compromised mobility, reduced quality of life and increased mortality. However, the underlying immune dysregulation in AS remains poorly understood. We comprehensively profiled the peripheral immune landscape of 30 patients with active AS, all of whom were TNF-α blocker-naïve, capturing the immune profile during the active disease phase without biologic interference. Using advanced 11-color flow cytometry and FlowSOM clustering, 584 immunophenotypes were analyzed in AS and 30 age-and sex-matched healthy controls, with emphasis on both cellular composition and functional characteristics. AS patients displayed a distinctive functional "activated-exhausted" immune phenotype, dominated by CD4+CD28+CD38+PD-1+ T cells and HLA-DR+CD38+CD4-CD8- double-negative (DN) T cells. DN T cells were significantly enriched in HLA-B27-positive patients, suggesting potential as a biomarker. Network analysis revealed seven central immune subsets associated with active disease, while functional assessment demonstrated impaired CD95+CD8+ T cell apoptosis and disrupted B-cell maturation. These findings provide a detailed functional immune map of biologic-naïve active AS, offering novel mechanistic insights and identifying candidate biomarkers for precision intervention. The online version contains supplementary material available at https://doi.org/10.1007/s43657-025-00308-8.
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BibTeX
@article{bai2026deep,
title = {{Deep Immunophenotyping Unravels the Double Negative T cells and PD-1-Mediated Inflammatory Exhaustion in Ankylosing Spondylitis.}},
author = {Lu Bai and Jian Gao and Yunyun Xu and Yuexin Yu and Jing Liu and Mathias Hochgerner and Hejian Zou and Xingdong Chen and Feng Qian and Hongjun He and Jiucun Wang},
journal = {Phenomics (Cham, Switzerland)},
year = {2026},
month = aug,
doi = {10.1007/s43657-025-00308-8},
url = {https://europepmc.org/article/MED/42999461},
note = {CC BY},
}
RIS
TY - JOUR
TI - Deep Immunophenotyping Unravels the Double Negative T cells and PD-1-Mediated Inflammatory Exhaustion in Ankylosing Spondylitis.
AU - Lu Bai
AU - Jian Gao
AU - Yunyun Xu
AU - Yuexin Yu
AU - Jing Liu
AU - Mathias Hochgerner
AU - Hejian Zou
AU - Xingdong Chen
AU - Feng Qian
AU - Hongjun He
AU - Jiucun Wang
PY - 2026
DA - 2026/08/13
JO - Phenomics (Cham, Switzerland)
DO - 10.1007/s43657-025-00308-8
UR - https://europepmc.org/article/MED/42999461
AB - Ankylosing spondylitis (AS) is a chronic, immune-mediated inflammatory disorder primarily affecting the axial skeleton. It is characterized by bony fusion and syndesmophyte formation of the spine, leading to compromised mobility, reduced quality of life and increased mortality. However, the underlying immune dysregulation in AS remains poorly understood. We comprehensively profiled the peripheral immune landscape of 30 patients with active AS, all of whom were TNF-α blocker-naïve, capturing the immune profile during the active disease phase without biologic interference. Using advanced 11-color flow cytometry and FlowSOM clustering, 584 immunophenotypes were analyzed in AS and 30 age-and sex-matched healthy controls, with emphasis on both cellular composition and functional characteristics. AS patients displayed a distinctive functional "activated-exhausted" immune phenotype, dominated by CD4+CD28+CD38+PD-1+ T cells and HLA-DR+CD38+CD4-CD8- double-negative (DN) T cells. DN T cells were significantly enriched in HLA-B27-positive patients, suggesting potential as a biomarker. Network analysis revealed seven central immune subsets associated with active disease, while functional assessment demonstrated impaired CD95+CD8+ T cell apoptosis and disrupted B-cell maturation. These findings provide a detailed functional immune map of biologic-naïve active AS, offering novel mechanistic insights and identifying candidate biomarkers for precision intervention. The online version contains supplementary material available at https://doi.org/10.1007/s43657-025-00308-8.
SN - 2730-583X
SN - 2730-5848
ER -