Single-cell RNA transcriptomic and plasma Lipidomic reveal the potential mechanisms of a Methotrexate-based therapy against Rheumatoid Arthritis

作者：Zhihua Yang, Qi Liang, Huasheng Liang, Wen‐Ying Chen, Chuanning Li, Yunting Xiao, Youbang Liang, Maojie Wang, Xi Tan, Xiaodong Wu, Yanzhao Lin, Xiumin Chen, Qingchun Huang, Zehuai Wen, Runyue Huang · 发表于：Phytomedicine · 年份：2023 · DOI：10.1016/j.phymed.2023.154816 · 被引用次数：11 · 研究领域：Single-cell and spatial transcriptomics、Rheumatoid Arthritis Research and Therapies、Immune cells in cancer

OBJECTIVE: To assess whether a Methotrexate-based therapy could achieve more clinical benefit, we arranged a Simon 2-Stage Phase 1 Trial. Single-cell RNA sequencing and lipidomic profiling were performed to reveal the potential mechanisms. METHODS: Patients were enrolled in an open-label, Simon 2-stage, single-center, single-arm trial at Guangdong Provincial Hospital of Chinese Medicine. Main inclusion criteria were defined as follows: Aged 18 to 70, low to medium disease activity, fulfilled the RA classification criteria of EULAR/ACR 2010. Patients received the oral medication of MTX 10-15 mg weekly and natural product granules twice a day. Primary outcome was the American College of Rheumatology (ACR) 20% preliminary definition of improvement. Single-cell RNA sequencing(scRNA-seq) on peripheral blood mononuclear cells (PBMCs) was used to show the aberrant metabolism before and after the trial. Plasma lipidomic profiling quantified the lipid changes caused by this MTX-based therapy. Finally, post-hoc analysis on responders and non-responders were used for further analysis. RESULTS: Between October 2020 and June 2022, 46 patients received treatment, while 42 finished follow-ups. 27 of 46 (58.70%) patients achieved ACR20, and significant changes were observed in several secondary outcomes. Comparative scRNA-seq analysis before and after the treatment revealed that lipidomic metabolism was broadly downregulated. Plasma lipidomic profiling reveals that 40 lipids were observed si...