Vasculitis & polymyalgia rheumatica
Investigating potential biomarkers associated with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis using Mendelian randomization and transcriptomic analysis
Authors' conclusion
PDK4, PPARGC1A, FN1, and PSMB10 were identified as biomarkers causally related to AAV
Study context
- Population
- AAV-related datasets (GSE104,948 and GSE108,109); renal biopsies from patients with ANCA-associated glomerulonephritis
- Comparison
- AAV vs normal
- Outcome
- Novel biomarkers for AAV
Methodological detailsMendelian randomization, transcriptomic analysis, machine learning, immunofluorescence validation
- Mendelian randomization
- Transcriptomic analysis
- Machine learning
- Immunofluorescence validation
Main finding
As reported in the abstract
Biomarkers causally related to AAV (Mendelian randomization (MR), IVW)
- PDK4, PSMB10 (IVW, OR > 1, P < 0.05)
- PPARGC1A, FN1 (IVW, OR < 1, P < 0.05)
- PDK4 and PPARGC1A significantly down-regulated in AAV vs normal; FN1 and PSMB10 the opposite
Further findings
ANN based on biomarkers
- Robust predictive capacity for assessing AAV risk
Enrichment and immune infiltration
- Co-enrichment of PDK4 and PPARGC1A in 'butanoate metabolism' and 'fatty acid metabolism'
- Strong positive correlation of naive B cells with PDK4; substantial negative correlation with PSMB10
Molecular regulatory network
- XIST regulates PDK4, FN1 and PPARGC1A through hsa-miR-103a-3p, hsa-miR-1271-5p and hsa-miR-23a-3p
Predicted drugs
- Drugs with potential targeting of 4 biomarkers (e.g., dacarbazine, dichloroacetate, bortezomib)
- 19
Validation in renal biopsies (ANCA-associated glomerulonephritis vs controls)
- Decreased glomerular expression of PDK4 and PPARGC1A; increased expression of FN1 and PSMB10
Original publication
Investigating potential biomarkers associated with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis using Mendelian randomization and transcriptomic analysis. Arthritis Res Ther. Published 20 August 2025. doi:10.
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