Immune profiling-based targeting of pathogenic T cells with ustekinumab in ANCA-associated glomerulonephritis.

ABSTRACT: 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 dr

SUBMITTER: Engesser J 

PROVIDER: S-EPMC11413367 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature