王瀞瑢

• Present study was honored with an outstanding award by the Taiwan Genomic Medicine and Biomarker Society at the 2022 Multiomics and Precision Medicine Joint Conference and has been published in Clin Transl Med (October 2022, 12(10): e1066).

• Research interest of Jing-Rong Wang includes single-cell bioinformatics analysis, blood immune profiling, autoimmune diseases.

• Her current study focusses on prediction of cellular biologics' responses to therapy, utilizing blood immune profiles before treatments to offer optimal therapeutic strategies for patients and enable real-time response monitoring.

Exploring Ankylosing Spondylitis in Women: Breakthroughs via Multimodal Single-Cell Analysis

ing-Rong Wang (王瀞瑢)1,5#, Hsin-Hua Chen2,3#, Hsiao-Ni Sung1, Wen-Cheng Chao4, Kuan-Ting Liu5, Fang-Ping Lin1, Tai-Ming Ko1,5,6,7*

1 Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.

2Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.

3 School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.

4 Department of Critical Care Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.

5 Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan.

6 Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

7 Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu, Taiwan.

#Hsin‐Hua Chen and Jing‐Rong Wang contributed equally as the first authors.

Purpose: A chronic rheumatic disorder, Ankylosing spondylitis (AS) severely impacts life quality and causes significant disability, particularly in females. The role of various circulating immune cells in AS development is still largely unknown.

Materials and Methods: Utilizing droplet-based single-cell sequencing, we performed a multimodal analysis of PBMCs from female patients and gender-matched healthy subjects, encompassing unbiased transcriptome profiling, surface protein expression study, pseudotemporal trajectory examination, cell interaction analysis, and T-cell receptor repertoire evaluation at the single-cell level.

Results: By implementing multiple filtering techniques, we discerned consistent single-cell blood traits among the patients, revealing a unique T-cell state with increased GIMAP7 and decreased NFKBIA. Validation with public scRNA-Seq datasets demonstrated that these markers are absent in male AS patients. We also characterized several key cell-surface markers (CD24+CD274+PD1+CD16-) and highly abundant T-cell clonotypes in this specific T-cell subset (NFKBIA- GIMAP7+). Our trajectory inference analysis unveiled a reverse pattern in T-cell differentiation trajectories in female patients compared to healthy individuals. Additionally, we ascertained a critical VEGI signaling interaction between T-cells and NK cells, exclusive to female patients, possibly shaping their distinct T-cell state.

Conclusion: Our findings show that NK cells might drive T cells to differentiate into a unique subset, contributing to AS development in female patients through VEGI signaling. Identifying these specific immune responses in female AS patients is crucial for developing personalized therapies and opening avenues for treatment plans that are more tailored and potentially more beneficial to patients.