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drug-reactions

Can spatial proteomics find a TEN therapy?

Nordmann TM, Anderton H, Hasegawa A, et al. · Nature · 2024

Open access · cc by · source: Europe PMC

Deep visual proteomics of drug-reaction skin (>5,000 proteins/cell type) revealed interferon–STAT1 programs in TEN; JAK inhibitors improved disease in mouse models.

Key findings

TEN showed enriched type I/II interferon signatures and phosphorylated STAT1. Tofacitinib, baricitinib, abrocitinib, or upadacitinib ameliorated clinical/histological severity in mice. TEN involves >30% epidermal detachment and lacked effective therapy.

Methodology

Used deep visual proteomics on archived FFPE biopsies across CADR severities to quantify keratinocyte and immune-cell proteomes, then tested oral JAKis in two TEN mouse models.

Limitations

Mouse efficacy and proteomic nomination are not a completed large randomized TEN trial; dosing/safety in critically ill TEN patients need careful clinical evaluation.

How this study connects

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