Exploring the shared molecular mechanisms between systemic lupus erythematosus and primary Sjögren's syndrome based on integrated bioinformatics and single-cell RNA-seq analysis

Yanling Cui; Huina Zhang; Zhen Wang; Bangdong Gong; Hisham Al-Ward; Yaxuan Deng; Orion Fan; Junbang Wang; Wenmin Zhu; Yi Eve Sun

doi:10.3389/fimmu.2023.1212330

Exploring the shared molecular mechanisms between systemic lupus erythematosus and primary Sjögren's syndrome based on integrated bioinformatics and single-cell RNA-seq analysis

Front Immunol. 2023 Aug 8:14:1212330. doi: 10.3389/fimmu.2023.1212330. eCollection 2023.

Authors

Yanling Cui^{1

2}, Huina Zhang^{1

2}, Zhen Wang^{1

2}, Bangdong Gong³, Hisham Al-Ward^{1

2}, Yaxuan Deng^{1

2}, Orion Fan^{1

2}, Junbang Wang¹, Wenmin Zhu¹, Yi Eve Sun^{1

2}

Affiliations

¹ Stem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
² Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
³ Division of Rheumatology, Tongji Hospital of Tongji University School of Medicine, Shanghai, China.

Abstract

Background: Systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) are common systemic autoimmune diseases that share a wide range of clinical manifestations and serological features. This study investigates genes, signaling pathways, and transcription factors (TFs) shared between SLE and pSS.

Methods: Gene expression profiles of SLE and pSS were obtained from the Gene Expression Omnibus (GEO). Weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis were conducted to identify shared genes related to SLE and pSS. Overlapping genes were then subject to Gene Ontology (GO) and protein-protein interaction (PPI) network analyses. Cytoscape plugins cytoHubba and iRegulon were subsequently used to screen shared hub genes and predict TFs. In addition, gene set variation analysis (GSVA) and CIBERSORTx were used to calculate the correlations between hub genes and immune cells as well as related pathways. To confirm these results, hub genes and TFs were verified in microarray and single-cell RNA sequencing (scRNA-seq) datasets.

Results: Following WGCNA and limma analysis, 152 shared genes were identified. These genes were involved in interferon (IFN) response and cytokine-mediated signaling pathway. Moreover, we screened six shared genes, namely IFI44L, ISG15, IFIT1, USP18, RSAD2 and ITGB2, out of which three genes, namely IFI44L, ISG15 and ITGB2 were found to be highly expressed in both microarray and scRNA-seq datasets. IFN response and ITGB2 signaling pathway were identified as potentially relevant pathways. In addition, STAT1 and IRF7 were identified as common TFs in both diseases.

Conclusion: This study revealed IFI44L, ISG15 and ITGB2 as the shared genes and identified STAT1 and IRF7 as the common TFs of SLE and pSS. Notably, the IFN response and ITGB2 signaling pathway played vital roles in both diseases. Our study revealed common pathogenetic characteristics of SLE and pSS. The particular roles of these pivotal genes and mutually overlapping pathways may provide a basis for further mechanistic research.

Keywords: TFs; bioinformatics; hub genes; primary Sjögren’s syndrome; scRNA-seq; systemic lupus erythematosus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD18 Antigens
Computational Biology
Genes, Overlapping
Humans
Lupus Erythematosus, Systemic* / genetics
Single-Cell Gene Expression Analysis
Sjogren's Syndrome* / genetics
Ubiquitin Thiolesterase

Substances

CD18 Antigens
USP18 protein, human
Ubiquitin Thiolesterase

Grants and funding

This work was supported by the National Key R&D Program of China (2020YFC2002804), the State Key Program of the Nation al Natural Science Foundation of China (82030035), the Foundation of Shanghai Municipal Education Commission (2019-01- 07-00-07-E00055) and the Key R&D Program of Jiangsu (BE2020026).