GEO series
Immune profiling-based targeting of pathogenic T cells with ustekinumab in ANCA-associated glomerulonephritis
GSE250138
Homo sapiens
Expression profiling by high throughput sequencing; Other
23 samples
Submitted 2024/06/28
Platform GPL24676
Summary
Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is a life-threatening autoimmune disease that often results in kidney failure caused by crescentic glomerulonephritis (ANCA-GN). To date, treatment of most patients with ANCA-GN relies on unspecific immunosuppressive agents that harbor serious adverse effects and limited efficiency. Using spatial and single-cell transcriptome analysis we characterized inflammatory niches in the kidneys of 34 patients with ANCA-GN and idenjpgied proinflammatory cytokine producing CD4+ and CD8+ T cells as a key pathogenic tissue signature. By employing digital pharmacology we then idenjpgied ustekinumab, a monoclonal antibody targeting IL-12 and IL-23 in these T cells, as promising therapeutic avenue. Based on these findings, four patients with relapsing ANCA-GN were treated with ustekinumab in combination with low-dose cyclophosphamide. Ustekinumab was given subcutaneously (90 mg) at weeks 0, 4, 12, and 24 and clinical and renal response were evaluated at week 26. Treatment induced substantial clinical response in all ANCA-GN patients, with improvements in kidney function, and Birmingham Vasculitis Activity Score, and was well tolerated. Our findings suggest that the pathogenesis-based treatment of ANCA-GN patients with ustekinumab is efficacious and warrants further investigation in clinical trials.
Published in
Engesser J, Khatri R, Schaub DP et al.
· Nature communications 2024
· PMID 39300109
· doi:10.1038/s41467-024-52525-w
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE250138_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 23 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1052093 and SRA study SRP477846. Searching any of these in the dataset finder brings you back here.
Study design
23 conditions, each sampled once — no replicated groups
Read from 23 sample titles: 23 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM7974475 V4_B
- GSM7974476 V6_B
- GSM7974477 V4_D
- GSM7974478 V5_A
- GSM7974479 V6_C
- GSM7974480 V6_A
- GSM7974481 V5_D
- GSM7974482 V3_A
- GSM7974483 V2_D
- GSM7974484 V4_A
- GSM7974485 V1_D
- GSM7974486 V2_C
- GSM7974487 V5_C
- GSM7974488 V5_B
- GSM7974489 V1_A
- GSM7974490 V2_B
- GSM7974491 V3_C
- GSM7974492 V3_D
- GSM7974493 V4_C
- GSM7974494 V6_D
- GSM7974495 CTRL1_B
- GSM7974496 CTRL1_C
- GSM7974497 CTRL1_D
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