Spatial transcriptomics reveals injury responsive compartments and coordinated immune fibrotic signaling in ANCA associated renal vasculitis

Abstract

ANCA-associated vasculitis (AAV) often presents with rapidly progressive glomerulonephritis, yet how immune and stromal programmes are organised within kidney tissue remains unclear. We applied spatial transcriptomics to renal cortex biopsies from patients with AAV of varying disease severity and normal-histology controls, generating a spatial map that localizes disease programmes in situ. Four disease-responsive compartments--immune/interstitial fibroblasts (IM/Fib), glomeruli, myofibroblasts, and vascular compartments--showed distinct compartment-specific signatures that correlated with histopathology at the patient level. We also identify coordinated immune-fibrotic signaling linked to severity. Within IM/Fib, the CXCR4-CD74 receptor complex co-localised with IgM cells, and lumican (LUM) co-localised with collagen I/III; both were validated by immunofluorescence and associated with fibrotic injury. These tissue-anchored signatures constitute candidate diagnostic/prognostic biomarkers, and show the utility of this foundational spatial transcriptomics map to generate testable hypotheses which will guide validation in larger, stratified, treatment-annotated cohorts.