Abstract: TH-PO552
Single-Cell Spatial Resolution Transcriptomic Profiling in Lupus Membranous Nephritis
Session Information
- Glomerular Diseases: Omics, Biomarkers, and Tools
October 24, 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
- Avillach, Claire, Mass General Brigham Inc, Boston, Massachusetts, United States
- Giarraputo, Alessia, Mass General Brigham Inc, Boston, Massachusetts, United States
- Rosales, Ivy A., Mass General Brigham Inc, Boston, Massachusetts, United States
- Marcin, Jeremy M., Mass General Brigham Inc, Boston, Massachusetts, United States
- Brousaides, Nicole Lauren, Mass General Brigham Inc, Boston, Massachusetts, United States
- Colvin, Robert B., Mass General Brigham Inc, Boston, Massachusetts, United States
Group or Team Name
- Immunopathology Research Lab.
Background
Understanding the molecular pathways involved in membranous lupus nephritis (classV LN) is crucial for identifying diagnostic biomarkers and potential therapeutic targets.
Methods
Spatial transcriptomic technology with cellular resolution was employed to analyze the expression of 1,000 RNAs in kidney core biopsies from patients with classV LN (n=3) and PLA2R-associated membranous nephropathy (PLA2R-MN, n=3). Spatially resolved cells were classified into cell types and differential gene expression analysis was conducted using a negative binomial model.
Results
Spatial single-cell transcriptomic analysis was conducted on 33,195 cells from class V LN samples and 39,127 cells from PLA2R-MN samples. Gene expression analysis revealed a significant upregulation of multiple type I interferon-stimulated genes (ISGs) in lupus nephritis, including IFIMT1, OAS1, STAT1, and IFI27 (Figure1). Increased ISG expression was observed across the main glomerular cell subtypes (podocytes, glomerular endothelial cells, mesangial cells/fibroblasts) as well as in tubular epithelial cells (Figure2). Notably, there was no significant increased expression of interferon (IFN) alpha, beta, gamma genes nor their receptors in lupus nephritis.
Conclusion
In comparison to PLA2-R-MN, class V LN shows activation of the type I IFN pathway. Further studies are needed to determine the role of interferon pathway activation in kidney injury and its use as a possible diagnostic or prognostic biomarker or therapeutic target for class V lupus nephritis.