Kidney whole-transcriptome profiling in primary antiphospholipid syndrome reveals complement, interferons and...

Area of Science:

• Immunology
• Nephrology
• Genomics

Background:

• The pathogenesis of antiphospholipid syndrome (APS) is not fully understood.
• Kidney involvement is a significant complication in APS and systemic lupus erythematosus (SLE).
• Comparative transcriptome analysis can elucidate disease-specific molecular pathways.

Purpose of the Study:

• To compare kidney transcriptome profiles in primary APS, SLE, and control subjects.
• To identify differentially expressed genes and enriched pathways in APS kidney disease.
• To explore the role of innate immunity in APS nephropathy.

Main Methods:

• RNA sequencing was performed on kidney biopsies from APS (n=4), SLE (n=5), and control (n=3) individuals.
• Differential gene expression analysis (DGEA) was conducted.
• Enrichment analysis utilized Gene Ontology (GO), CORUM, KEGG, and Reactome pathway databases.

Main Results:

• Distinct kidney gene profiles were observed in APS compared to controls, and were similar to SLE.
• DGEA revealed significant upregulation of immune response, inflammatory response, and complement-related genes (C3, C4A, C4B) in APS vs controls.
• Interferon (IFN) signaling and neutrophil extracellular trap (NETs)-related genes were also upregulated in APS kidney tissues, similar to SLE.

Conclusions:

• Complement, interferon, and NETs-related genes are highly expressed in APS kidney tissues, mirroring SLE.
• These findings underscore the critical role of innate immunity in the pathogenesis of APS nephropathy.
• The identified pathways represent potential therapeutic targets for APS kidney disease.