Transcriptome sequencing reveals novel molecular features of SLE severity

Area of Science:

• Immunology
• Genomics
• Molecular Biology

Background:

• Systemic lupus erythematosus (SLE) is a complex autoimmune disease.
• SLE is characterized by autoantibodies, immune complex deposition, and organ damage.
• Identifying molecular drivers of SLE severity is crucial for targeted therapies.

Purpose of the Study:

• To identify molecular features and signaling pathways associated with SLE severity.
• To compare gene expression profiles between mild and severe SLE patient groups.
• To investigate the role of immune cell populations in SLE pathogenesis.

Main Methods:

• Transcriptome profiling using RNA sequencing (RNA-seq) on 45 SLE patients.
• Single-cell RNA sequencing (scRNA-seq) data analysis.
• Correlation analysis of gene expression with clinical parameters and immune cell infiltration (CIBERSORT).

Main Results:

• Identified 12 differentially expressed genes (DEGs) between mild and severe SLE, including upregulated CEACAM6, UCHL1, AMPH, and downregulated SORBS2, TRIM64B.
• Found significantly decreased regulatory T (Treg) cells in severe SLE (sSLE) patients.
• Observed a negative correlation between Treg cell frequency and AMPH expression, with AMPH primarily expressed in Treg cells.

Conclusions:

• Specific gene expression patterns and reduced Treg cell numbers are associated with SLE severity.
• AMPH may play a role in SLE pathogenesis, particularly in relation to Treg cell function.
• These findings provide potential molecular targets for managing SLE severity.