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Preprint
Multiomic single-cell sequencing defines tissue-specific responses in Stevens-Johnson Syndrome and Toxic epidermal necrolysis
bioRxiv
Cold Spring Harbor Laboratory
2024
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.
Details
- Title
- Multiomic single-cell sequencing defines tissue-specific responses in Stevens-Johnson Syndrome and Toxic epidermal necrolysis
- Authors/Creators
- Andrew Gibson - Murdoch University, Centre for Molecular Medicine and Innovative TherapeuticsRamesh RamRama Gangula - Vanderbilt University Medical CenterYueran LiEric Mukherjee - Vanderbilt University Medical CenterAmy M. Palubinsky - Vanderbilt University School of MedicineChelsea N. Campbell - Vanderbilt University School of MedicineMichael ThorneK.C. Konvinse - Vanderbilt University Medical CenterPhuti ChoshiPooja Deshpande - Murdoch UniversitySarah PendrettiRichard T O'NeilCelestine N Wanjalla - Vanderbilt University Medical CenterSpyros A Kalams - Vanderbilt University Medical CenterSilvana Gaudieri - Murdoch University, Institute for Immunology and Infectious DiseasesRannakoe J LehloenyaSamuel S. BaillinAbha Chopra - Murdoch University, Centre for Molecular Medicine and Innovative TherapeuticsJason A. Trubiano - Austin HospitalJonny G PeterSimon MallalElizabeth Phillips
- Publication Details
- bioRxiv
- Publisher
- Cold Spring Harbor Laboratory
- Identifiers
- 991005641569207891
- Copyright
- The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases; Centre for Molecular Medicine and Innovative Therapeutics
- Resource Type
- Preprint
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