Lupus & antiphospholipid syndrome
Integrative spatial multiomics analysis reveals regulatory mechanisms of VCAM1+ proximal tubule cells in lupus nephritis
Authors' conclusion
Collectively, our findings characterise PT_VCAM1 cells as injury-responsive cell states that contribute to the inflammatory and fibrotic niche in LN, linking genetic predisposition to cellular injury and disease progression.
Study context
- Population
- Kidney biopsy samples from patients with lupus nephritis (LN) and controls; East Asian systemic lupus erythematosus (SLE) genome-wide association studies (GWAS) data (208,370 samples)GWAS 208,370 samples
- Comparison
- LN kidney biopsies vs controls
- Outcome
- Regulatory mechanisms underlying region-specific kidney lesions and tubular damage in LN
Methodological detailssingle-cell multiome, spatial transcriptomics, integrative GWAS analysis, multiplex immunohistochemistry (mIHC) validation, in vitro lentiviral-mediated transcription factor overexpression, functional stimulation assays
- Single-cell multiome
- Spatial transcriptomics
- Integrative GWAS analysis
- mIHC validation
- In vitro lentiviral-mediated transcription factor overexpression
- Functional stimulation assays
Main finding
As reported in the abstract
- VCAM1-expressing proximal tubule (PT_VCAM1) cells are components of an LN-specific inflammatory niche (niche 5) in the kidney cortex
- Interactions of PT_VCAM1 cells with myofibroblasts and immune cells in niche 5 promote their epithelial-mesenchymal transition (in silico and in vitro)
- Trajectory analysis suggested PT_VCAM1 cells originate from a failed-repair pathway in proximal tubule cells, regulated by transcriptional networks involving BACH2
- SLE-associated risk SNPs linked to PT_VCAM1-specific cis-regulatory elements, incl. SNPs in the distal enhancer of the BMP2K locus establishing a BACH2 motif
Original publication
Integrative spatial multiomics analysis reveals regulatory mechanisms of VCAM1+ proximal tubule cells in lupus nephritis. Ann Rheum Dis. Published 19 September 2025. doi:10.
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