Transcriptomic profiling reveals immune pathway dysregulation and key interferon-responsive genes in Systemic Lupus...

Area of Science:

• Immunology
• Genomics
• Computational Biology

Background:

• Systemic Lupus Erythematosus (SLE) is an autoimmune disease marked by chronic inflammation and multi-organ damage.
• A significant type I interferon (IFN) signature is characteristic of SLE pathogenesis.
• Understanding immune-specific molecular drivers is crucial for developing effective SLE treatments.

Purpose of the Study:

• To identify immune-specific molecular drivers of Systemic Lupus Erythematosus (SLE) through transcriptomic profiling.
• To elucidate the role of differentially expressed genes (DEGs) and associated pathways in SLE pathogenesis.
• To explore potential therapeutic targets and biomarkers for SLE management.

Main Methods:

• RNA sequencing (RNA-seq) was performed on 117 samples (99 SLE patients, 18 healthy controls).
• Differential gene expression analysis was conducted using DESeq2, identifying 2150 DEGs.
• Pathway enrichment analysis (Reactome, Gene Ontology) was used to interpret the functional significance of DEGs.

Main Results:

• 2150 differentially expressed genes (DEGs) were identified, with 1361 upregulated and 789 downregulated (FDR<0.01, |log₂FC=>1).
• Immune-related DEGs were enriched in pathways including cytokine signaling, interferon response, and innate immune activation.
• Interferon-stimulated genes (ISGs) and genes involved in ubiquitination and cytokine signaling were highlighted as central regulatory nodes.

Conclusions:

• Type I interferon (IFN) signaling and associated immune pathways are key drivers of SLE.
• Specific genes like HERC5, HERC6, and IL5RA may serve as biomarkers for SLE disease activity.
• Targeting type I IFN pathways presents a promising therapeutic strategy for SLE, supporting precision medicine approaches.