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

Here, we applied spatial transcriptomics to renal biopsies from pediatric patients with AAV representing distinct histological classes defined by the Berden classification (4 control, 2 focal, and 3 non-focal cases), generating an in situ map of localized disease programs.

Four disease-associated compartments—immune/interstitial fibroblasts (IM/Fib), glomeruli, myofibroblasts, and vascular compartments—showed distinct compartment-specific signatures that correlated with patient-level histopathology. We further identified coordinated immune–fibrotic signaling associated with different histopathological classes. Within IM/Fib, the CXCR4–CD74 receptor complex co-localized with IgM⁺ cells, and lumican (LUM) co-localized with collagen I/III; both were validated by immunofluorescence and associated with fibrotic injury.