Immune-relevant genes of systemic lupus erythematosus by transcriptome profiling analysis

Juan Lv; Lu Chen; Xin Wang; Qi Gao; Ling Zhao

doi:10.1016/j.cyto.2022.155975

Immune-relevant genes of systemic lupus erythematosus by transcriptome profiling analysis

Cytokine. 2022 Oct:158:155975. doi: 10.1016/j.cyto.2022.155975. Epub 2022 Aug 11.

Authors

Juan Lv¹, Lu Chen², Xin Wang², Qi Gao², Ling Zhao³

Affiliations

¹ Department of Critical Care Medicine, The First Hospital of Jilin University, No.71, Xinmin Street, Changchun 130021, China.
² Department of Rheumatology, The First Hospital of Jilin University, No. 71, Xinmin Street, Changchun 130021, China.
³ Department of Rheumatology, The First Hospital of Jilin University, No. 71, Xinmin Street, Changchun 130021, China. Electronic address: zhaoling17@jlu.edu.cn.

PMID: 35964416
DOI: 10.1016/j.cyto.2022.155975

Abstract

Objective: Our study aimed to reveal the roles of long noncoding RNA (lncRNA) and immune-relevant genes in systemic lupus erythematosus (SLE).

Methods: Expression profiling dataset GSE65391 consisted of 72 healthy blood samples and 924 SLE blood samples was downloaded from the Gene Expression Omnibus. Differentially expressed RNAs (DERs) in SLE samples were identified using the Limma package. Immune-relevant DERs were uncovered after assessing the immune cell infiltration types of different samples. Modules significantly related to the disease were extracted via weighted gene co-expression network analysis (WGCNA), followed by module-trait analysis. LncRNA-mRNA co-expression network was constructed for DERs in immune-relevant modules. Genes related to SLE were further revealed via the Comparative Toxicogenomics Database (CTD). Validation assay was conducted by another independent expression profiling dataset, GSE46907 (consisted of 5 healthy blood samples and 5 SLE blood samples) and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis of 15 healthy blood samples and 15 SLE blood samples.

Results: A total of 606 DERs, including 19 lncRNAs and 587 mRNAs, were identified. Obvious differences were observed in the proportions of 20 immune cell types, and 378 immune-relevant DERs were revealed. Genes in the lncRNA-mRNA co-expression network were significantly enriched in primary immunodeficiency, hematopoietic cell lineage, B cell receptor signaling pathway, SLE (up-regulated FCGR3A, down-regulated CD40LG, up-regulated HIST1H2BE, down-regulated human leukocyte antigen [HLA]-DOA, down-regulated HLA-DOB, up-regulated HIST1H3D, and up-regulated HIST1H2BC), and intestinal immune network for IgA production. SLE-related gene, CD40LG, retrieved from CTD has co-expression interactions with seven differentially expressed lncRNAs (HCG27, LINC02555, LINC02210, DHRS4-AS1, MIR600HG, DANCR, and LINC01278). CD40LG and HLA-DOA, were observed down-regulated, and FCGR3A, and HIST1H2BE were up-regulated in validation dataset GES46907. Moreover, CD40LG was validated to be down-regulated using qRT-PCR.

Conclusions: Our results provide new insight in understanding the pathogenesis of SLE and might be helpful for developing new therapeutic approaches of SLE by modulating immune response.

Keywords: Immune cell; Module; Systemic lupus erythematosus.

Publication types

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

MeSH terms

Gene Expression Profiling / methods
Gene Regulatory Networks
Humans
Lupus Erythematosus, Systemic* / genetics
Lupus Erythematosus, Systemic* / pathology
RNA, Long Noncoding* / genetics
RNA, Long Noncoding* / metabolism
RNA, Messenger / genetics
RNA, Messenger / metabolism
Transcriptome / genetics

Substances

RNA, Long Noncoding
RNA, Messenger