Circulating miRNAs as Potential Noninvasive Biomarkers for ANCAassociated Glomerulonephritis

Matic Bošnjak¹Emanuela Bostjancic¹Željka Večerić-Haler^2,3Jakob Tomšič¹Živa Pipan Tkalec¹Kojc Nika^1*

• ¹Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
• ²Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
• ³Department of Nephrology, University Medical Centre Ljubljana, Ljubljana, Slovenia

Introduction. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by necrotizing small vessel vasculitis that frequently manifests as glomerulonephritis (AAV-GN). An accurate noninvasive biomarker reflecting active AAV-GN remains elusive. The knowledge of microRNAs (miRNAs), which have been considered as disease-specific biomarkers, is scarce and lacks validated data in AAV. Methods. This study validated a renal tissue expression profile of candidate miRNAs specific to AAV-GN selected through prior screening using independent cohorts. The analysis was extended to serum samples to explore the potential of a circulating miRNA panel as a noninvasive biomarker for active AAV-GN. To substantiate the findings, we correlated the molecular data with clinical and histologic markers of AAV-GN activity. Results. We identified miR-21-3p, miR-181a-5p, and miR-181d-5p as potential biomarkers distinguishing AAV-GN from non-AAV renal diseases and healthy controls. In addition, MiR-21-3p and miR-181d-5p correlated with the presence of active AAV-GN, while miR-181a-5p differentiated AAV-GN subtypes based on ANCA antigen specificity. ROC curve analysis demonstrated that the combined serum expression of miR-21-3p and miR-181a-5p reliably distinguished AAV-GN from other renal pathologies, including ANCA-positive cases without histologic evidence of AAV-GN. Notably, validated miRNA expression did not differ significantly between renal-limited and systemic AAV, reinforcing the concept of AAV as a systemic disease.Conclusion. Our findings highlight the potential of circulating miRNA expression signature as a noninvasive biomarker for ongoing AAV-GN in the appropriate setting. Larger confirmatory studies are essential to support the clinical application of miRNA-based biomarkers in AAV-GN diagnostics and disease monitoring.