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

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

Immune dysregulation is a hallmark of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), particularly in the kidney; however, the spatial organization of renal microenvironments remains poorly understood. 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. These tissue-anchored signatures represent potential disease-associated molecular features with possible diagnostic relevance, and highlight the value of this foundational spatial transcriptomics map for generating testable hypotheses to be further evaluated in larger, stratified, treatment-annotated cohorts.

Datasets3
Size~50 MB
AssayVisium
Samplehuman · cortex of kidney
KindComparison
PMID:42602048 ↗
Python · lamindb
import lamindb as ln
import spatialdata as sd

coll = ln.Collection.get(key="geo-gse302677")
coll.ordered_artifacts.df()                 # the 3 members, ordered

# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()]

# …or load each straight into memory as a SpatialData object:
sdatas = {a.key: sd.read_zarr(a.cache()) for a in coll.ordered_artifacts.all()}
Open in Vitessce
Visium
Human cortex of kidney
GSM9108684
human cortex of kidney anti-neutrophil cytoplasmic antibody-associated vasculitis 11 MB 892 obs bronze H&E
TechnologyVisium
Organismhuman
Tissuecortex of kidney
Conditionanti-neutrophil cytoplasmic antibody-associated vasculitis
Size11 MB
Obs892
Magnificationother · 3.420 µm/px
bronze H&E Open in Vitessce
Open in Vitessce
Visium
Human cortex of kidney
GSM9108683
human cortex of kidney 14 MB 1,413 obs bronze H&E
TechnologyVisium
Organismhuman
Tissuecortex of kidney
Size14 MB
Obs1,413
Magnificationother · 3.738 µm/px
bronze H&E Open in Vitessce
Open in Vitessce
Visium
Human cortex of kidney
GSM9108685
human cortex of kidney anti-neutrophil cytoplasmic antibody-associated vasculitis 25 MB 1,277 obs bronze H&E
TechnologyVisium
Organismhuman
Tissuecortex of kidney
Conditionanti-neutrophil cytoplasmic antibody-associated vasculitis
Size25 MB
Obs1,277
bronze H&E Open in Vitessce

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