Abstract: SA-PO0744
Transcriptomic Profiling Reveals Mast-Cell Signatures and Active Immune Processes in Chronic ANCA-Associated Glomerulonephritis
Session Information
- Glomerular Diseases: Profiling Through Multiomics
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Brilland, Benoit, Centre Hospitalier Universitaire d'Angers, Angers, Pays de la Loire, France
- Gnemmi, Viviane, Centre Hospitalier Universitaire de Lille, Lille, Hauts-de-France, France
- Quemeneur, Thomas, CH de valenciennes, Valenciennes, France
- Vandenbussche, Cyrille, CH de valenciennes, Valenciennes, France
- Merillon, Nathalie, Centre Hospitalier Universitaire d'Angers, Angers, Pays de la Loire, France
- Despre, Maïa, Centre Hospitalier Universitaire d'Angers, Angers, Pays de la Loire, France
- Piccoli, Giorgina B., Centre Hospitalier du Mans, Le Mans, Pays de la Loire, France
- Langlais, David, McGill University, Montreal, Quebec, Canada
- Blanco, Patrick, Centre Hospitalier Universitaire de Bordeaux, Talence, Nouvelle-Aquitaine, France
- Augusto, Jean Francois, Centre Hospitalier Universitaire d'Angers, Angers, Pays de la Loire, France
- Copin, Marie-Christine, Centre Hospitalier Universitaire d'Angers, Angers, Pays de la Loire, France
Group or Team Name
- Maine-Anjou Registry Research Group.
Background
In ANCA-associated glomerulonephritis (AAV-GN), histopathological classifications guide prognosis but the molecular mechanisms underlying different histopathological patterns remain poorly understood. We conducted a retrospective study to integrate transcriptomic signatures with histopathological findings, aiming to refine our understanding of AAV-mediated renal injury, identify potential therapeutic targets and improve prognostication.
Methods
We performed targeted RNA expression profiling of 750 immune-related genes using NanoString technology on kidney biopsy specimens from 199 AAV-GN patients selected from the Maine-Anjou and RENVAS registries. Transcriptomic signatures were analyzed in relation to glomerular lesions (normal, crescentic, sclerotic), Berden classification, tubulointerstitial involvement, Renal Risk Score and ANCA Kidney Risk Score. pathway enrichment analyses identified key molecular signals. Immune cell deconvolution was performed to estimate leukocyte subsets. Gene-based signatures for predicting histological features were developed using LASSO regression.
Results
Transcriptomic profiles revealed robust immune activation across all histopathological classes. Contrary to the notion of “burnt-out” lesions, sclerotic glomeruli displayed strong expression of immunoinflammatory pathways, including TGF-β, mTOR, and immunometabolism pathways. Mast cell–related genes (e.g., CPA3, TPSAB1/B2) were enriched in advanced lesions (sclerotic glomeruli and interstitial fibrosis). Tubulointerstitial damage showed a gradient of innate and adaptive immune responses. Gene-based signatures accurately predicted histological features (R-squared ≥ 0.88).
Conclusion
This study highlights previously unrecognized molecular complexity in AAV-GN, identifying mast cells as potential mediators of chronic kidney damage and showing that even sclerotic lesions harbor immune activation. These findings provide new insights into disease mechanisms and identify novel therapeutic targets for personalized medicine approaches in AAV-GN.