Abstract: SA-PO0745
Type I Interferon Signature Distinguishes ANCA-Associated Vasculitis Phenotypes and Predicts Kidney Prognosis
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
- Despre, Maïa, Centre Hospitalier Universitaire d'Angers, Angers, Pays de la Loire, France
- Khatri, Robin, Hamburg Center for Translational Immunology, Hamburg, Germany
- Quemeneur, Thomas, CH de Valenciennes, Valenciennes, France
- Vandenbussche, Cyrille, CH de Valenciennes, Valenciennes, France
- Piccoli, Giorgina B., Centre Hospitalier du Mans, Le Mans, Pays de la Loire, France
- Gnemmi, Viviane, Centre Hospitalier Universitaire de Lille, Lille, Hauts-de-France, France
- Blanco, Patrick, Centre Hospitalier Universitaire de Bordeaux, Talence, Nouvelle-Aquitaine, France
- Copin, Marie-Christine, Centre Hospitalier Universitaire d'Angers, Angers, Pays de la Loire, France
- Langlais, David, McGill University, Montreal, Quebec, Canada
- Augusto, Jean Francois, Centre Hospitalier Universitaire d'Angers, Angers, Pays de la Loire, France
Group or Team Name
- Maine-Anjou Registry Research Group.
Background
ANCA-associated vasculitis (AAV) causes severe multisystemic organ damage. The main phenotypes, microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), share similarities but differ in clinical presentation and outcome. To uncover their molecular differences, we performed transcriptomic profiling of kidney tissue, then focused on type I interferon (IFN-I) pathway activation in kidney and blood and its clinical implications.
Methods
We analyzed two independent cohorts (Maine-Anjou and RENVAS registries) of 193 AAV patients with glomerulonephritis. NanoString nCounter transcriptomic profiling, qPCR, MxA immunohistochemistry, and serum inflammatory molecules quantification were conducted. Comparative analyses of MPA vs. GPA (and MPO-AAV vs. PR3-AAV) were validated using independent public datasets.
Results
Kidney transcriptomics revealed significant upregulation of the IFN-I pathway in MPA/MPO-AAV compared to GPA/PR3-AAV and controls. qPCR, immunohistochemistry, and analysis of external datasets confirmed these findings. IFN-I activation correlated with increased kidney fibrosis, independently of kidney function. High renal IFN-I signatures were linked to lower kidney survival, independently of kidney function and pathological scores. MPA kidneys also exhibited higher mast cell and T cell infiltration. Systemic analyses showed elevated IFNα and interferon-related inflammatory molecules in AAV, driven by a stronger IFN-I gene signature in MPA.
Conclusion
This study identifies a distinct IFN-I signature in MPA/MPO-AAV, underscoring its potential role in AAV heterogeneity and kidney pathology. IFN-I emerges as a potential prognostic biomarker and therapeutic target in AAV, particularly for MPA. Further studies are needed to clarify its mechanisms and explore IFN-I modulation in clinical trials.