Abstract: FR-PO827
Upregulation of Type I Interferon Pathway in Microscopic Polyangiitis
Session Information
- Glomerular Diseases: Inflammation and Immunology
October 25, 2024 | 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, CHU Angers, Angers, France
- Boizard-Moracchini, Andrea, Centre Hospitalier Universitaire de Bordeaux Groupe hospitalier Pellegrin, Bordeaux, Aquitaine, France
- Merillon, Nathalie, CHU Angers, Angers, France
- Piccoli, Giorgina B., Centre Hospitalier du Mans, Le Mans, Pays de la Loire, France
- Blanco, Patrick, Centre Hospitalier Universitaire de Bordeaux Groupe hospitalier Pellegrin, Bordeaux, Aquitaine, France
- Augusto, Jean Francois, CHU Angers, Angers, France
Group or Team Name
- Maine-Anjou Registry Research Group.
Background
The two main types of ANCA-associated vasculitis (AAV), microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), share common characteristics but also differ on many aspects (epidemiological, genetic, clinical, outcomes). To identify more specific targetable pathways, we compared the kidney transcriptome of MPA vs. GPA patients with AAV-glomerulonephritis (AAV-GN) and further characterized pathways of interest.
Methods
Immune gene transcript analysis (n = 750) was performed on RNA extracted from 97 adult AAV-GN kidney biopsies from the French Maine-Anjou Registry using NanoString technology (33 GPA, 64 MPA). Significant transcripts were examined to identify immune pathways of interest. We assessed IFNα levels with an ultrasensitive method. We also used a publicly available dataset to explore these identified pathways.
Results
Eight genes were found differentially expressed, all being upregulated in MPA (logFC > 1, q-value < 0.05). Seven belonged to the type I interferon (IFN-I) signaling pathway (Figure 1A). Nearly 20% of AAV-GN patients displayed elevated IFNα levels (Figure 1B, p = 0.02), which correlated with IFN-I activation in kidneys. Analyzing unpublished publicly available data, we identified a significantly more pronounced IFN-I related signature (expression of interferon regulated genes in PBMC and levels of CXCL10 in serum) in MPO-AAV vs PR3-AAV (Figure 1C).
Conclusion
We identified a type I interferon signature in AAV-GN, both in kidneys and in blood, especially in patients with MPA (or MPO-AAV) in comparison to GPA (or PR3-AAV). This is in line with previous evidence suggesting a role for IFN-I in AAV and especially in MPO-AAV. This signature may help gain a deeper understanding of the AAV-GN pathogenesis and provide insights for developing new therapeutic options.