biostudies-literatureEngesser JDeutsche ForschungsgemeinschaftDeutsche Forschungsgemeinschaft (German Research Foundation)8220https://www.ebi.ac.uk/biostudies/studies/S-EPMC11413367biostudies-literatureUnknown15(1)Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a life-threatening autoimmune disease that often results in kidney failure caused by crescentic glomerulonephritis (GN). To date, treatment of most patients with ANCA-GN relies on non-specific immunosuppressive agents, which may have serious adverse effects and be only partially effective. Here, using spatial and single-cell transcriptome analysis, we characterize inflammatory niches in kidney samples from 34 patients with ANCA-GN and identify proinflammatory, cytokine-producing CD4⁺ and CD8⁺ T cells as a pathogenic signature. We then utilize these transcriptomic profiles for digital pharmacology and identify ustekinumab, a monoclonal antibody targeting IL-12 and IL-23, as the strongest therapeutic drNature communicationsImmune profiling-based targeting of pathogenic T cells with ustekinumab in ANCA-associated glomerulonephritis.PMC11413367SFB1192Riedel JHHuber TBAsada NPeters APuelles VGKaffke AWiech TKrebs CFSchaub DPKhatri RSivayoganathan VPanzer UWenzel UOTurner JEZhao YGoldbeck-Strieder TMittrucker HWBonn SSultana ZPaust HJSteinmetz OMJauch-Speer SLHoxha EEngesser JfalseImmune profiling-based targeting of pathogenic T cells with ustekinumab in ANCA-associated glomerulonephritis.Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a life-threatening autoimmune disease that often results in kidney failure caused by crescentic glomerulonephritis (GN). To date, treatment of most patients with ANCA-GN relies on non-specific immunosuppressive agents, which may have serious adverse effects and be only partially effective. Here, using spatial and single-cell transcriptome analysis, we characterize inflammatory niches in kidney samples from 34 patients with ANCA-GN and identify proinflammatory, cytokine-producing CD4⁺ and CD8⁺ T cells as a pathogenic signature. We then utilize these transcriptomic profiles for digital pharmacology and identify ustekinumab, a monoclonal antibody targeting IL-12 and IL-23, as the strongest therapeutic dr2024-01-01T00:00:00Z2024 Sep2026-05-04T06:38:42.329Z2025-04-04T08:21:48.951ZS-EPMC114133673930010910.1038/s41467-024-52525-w