Arthritis Research & Therapy (May 2024)

Unraveling transcriptomic signatures and dysregulated pathways in systemic lupus erythematosus across disease states

  • Frank Qingyun Wang,
  • Li Shao,
  • Xiao Dang,
  • Yong-Fei Wang,
  • Shuxiong Chen,
  • Zhongyi Liu,
  • Yujing Mao,
  • Yuping Jiang,
  • Fei Hou,
  • Xianghua Guo,
  • Jian Li,
  • Lili Zhang,
  • Yuting Sang,
  • Xuan Zhao,
  • Ruirui Ma,
  • Kai Zhang,
  • Yanfang Zhang,
  • Jing Yang,
  • Xiwu Wen,
  • Jiong Liu,
  • Wei Wei,
  • Chuanpeng Zhang,
  • Weiyang Li,
  • Xiao Qin,
  • Yao Lei,
  • Hong Feng,
  • Xingtian Yang,
  • Chun Hing She,
  • Caicai Zhang,
  • Huidong Su,
  • Xinxin Chen,
  • Jing Yang,
  • Yu Lung Lau,
  • Qingjun Wu,
  • Bo Ban,
  • Qin Song,
  • Wanling Yang

DOI
https://doi.org/10.1186/s13075-024-03327-4
Journal volume & issue
Vol. 26, no. 1
pp. 1 – 13

Abstract

Read online

Abstract Objectives This study aims to elucidate the transcriptomic signatures and dysregulated pathways in patients with Systemic Lupus Erythematosus (SLE), with a particular focus on those persisting during disease remission. Methods We conducted bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) from a well-defined cohort comprising 26 remission patients meeting the Low Lupus Disease Activity State (LLDAS) criteria, 76 patients experiencing disease flares, and 15 healthy controls. To elucidate immune signature changes associated with varying disease states, we performed extensive analyses, including the identification of differentially expressed genes and pathways, as well as the construction of protein-protein interaction networks. Results Several transcriptomic features recovered during remission compared to the active disease state, including down-regulation of plasma and cell cycle signatures, as well as up-regulation of lymphocytes. However, specific innate immune response signatures, such as the interferon (IFN) signature, and gene modules involved in chromatin structure modification, persisted across different disease states. Drug repurposing analysis revealed certain drug classes that can target these persistent signatures, potentially preventing disease relapse. Conclusion Our comprehensive transcriptomic study revealed gene expression signatures for SLE in both active and remission states. The discovery of gene expression modules persisting in the remission stage may shed light on the underlying mechanisms of vulnerability to relapse in these patients, providing valuable insights for their treatment.

Keywords