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

Area of Science:

• Immunology
• Genomics
• Molecular Biology

Background:

• Systemic lupus erythematosus (SLE) is a complex autoimmune disease with poorly understood molecular mechanisms.
• Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in immune regulation and disease pathogenesis.
• Identifying key genes and pathways involved in SLE is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the roles of lncRNAs and immune-relevant genes in the pathogenesis of SLE.
• To identify differentially expressed RNAs (DERs) and their association with immune cell infiltration in SLE patients.
• To construct lncRNA-mRNA co-expression networks and explore potential SLE-related genes.

Main Methods:

• Analysis of gene expression profiling datasets (GSE65391 and GSE46907) from SLE and healthy individuals.
• Identification of DERs using Limma package and immune cell infiltration analysis.
• Weighted gene co-expression network analysis (WGCNA) and lncRNA-mRNA co-expression network construction.
• Validation of key gene expression using quantitative reverse transcription-polymerase chain reaction (qRT-PCR).

Main Results:

• 606 DERs, including 19 lncRNAs and 587 mRNAs, were identified in SLE samples.
• 378 immune-relevant DERs were found, with significant enrichment in pathways like primary immunodeficiency and SLE.
• Key genes such as CD40LG and HLA-DOA were down-regulated, while FCGR3A and HIST1H2BE were up-regulated in SLE, with CD40LG validation via qRT-PCR.

Conclusions:

• The study provides novel insights into the molecular mechanisms underlying SLE pathogenesis.
• Identified lncRNAs and immune genes, particularly CD40LG, may serve as potential biomarkers for SLE.
• Findings may contribute to the development of new therapeutic strategies for SLE by targeting immune responses.