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

Copyright © 2023 Cui, Zhang, Wang, Gong, Al-Ward, Deng, Fan, Wang, Zhu and Sun..

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.

Errataetall:

ErratumIn: Front Immunol. 2023 Dec 08;14:1339929. - PMID 38143754

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:14

Enthalten in:

Frontiers in immunology - 14(2023) vom: 01., Seite 1212330

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

Bioinformatics
CD18 Antigens
EC 3.4.19.12
Hub genes
Journal Article
Primary Sjögren’s syndrome
Research Support, Non-U.S. Gov't
ScRNA-seq
Systemic lupus erythematosus
TFs
USP18 protein, human
Ubiquitin Thiolesterase

Anmerkungen:

Date Completed 25.08.2023

Date Revised 25.12.2023

published: Electronic-eCollection

ErratumIn: Front Immunol. 2023 Dec 08;14:1339929. - PMID 38143754

Citation Status MEDLINE

doi:

10.3389/fimmu.2023.1212330

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM361126352