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Multiomic single-cell sequencing defines tissue-specific responses in Stevens-Johnson Syndrome and Toxic epidermal necrolysis
- PMID: 38405793
- PMCID: PMC10888802
- DOI: 10.1101/2023.11.26.568771
Multiomic single-cell sequencing defines tissue-specific responses in Stevens-Johnson Syndrome and Toxic epidermal necrolysis
Update in
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Multiomic single-cell sequencing defines tissue-specific responses in Stevens-Johnson syndrome and toxic epidermal necrolysis.Nat Commun. 2024 Oct 8;15(1):8722. doi: 10.1038/s41467-024-52990-3. Nat Commun. 2024. PMID: 39379371 Free PMC article.
Abstract
Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) is a rare but life-threatening cutaneous drug reaction mediated by human leukocyte antigen (HLA) class I-restricted CD8+ T-cells. To obtain an unbiased assessment of SJS/TEN cellular immunopathogenesis, we performed single-cell (sc) transcriptome, surface proteome, and TCR sequencing on unaffected skin, affected skin, and blister fluid from 17 SJS/TEN patients. From 119,784 total cells, we identified 16 scRNA-defined subsets, confirmed by subset-defining surface protein expression. Keratinocytes upregulated HLA and IFN-response genes in the affected skin. Cytotoxic CD8+ T-cell subpopulations of expanded and unexpanded TCRαβ clonotypes were shared in affected skin and blister fluid but absent or unexpanded in SJS/TEN unaffected skin. SJS/TEN blister fluid is a rich reservoir of oligoclonal CD8+ T-cells with an effector phenotype driving SJS/TEN pathogenesis. This multiomic database will act as the basis to define antigen-reactivity, HLA restriction, and signatures of drug-antigen-reactive T-cell clonotypes at a tissue level.
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References
-
- Chung W.H., et al. Medical genetics: a marker for Stevens-Johnson syndrome. Nature 428, 486 (2004). - PubMed
-
- Chung W.-H., et al. Granulysin is a key mediator for disseminated keratinocyte death in Stevens-Johnson syndrome and toxic epidermal necrolysis. Nature Medicine 14, 1343–1350 (2008). - PubMed
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