Villani, Axel Patrice; Rozieres, Aurore; Bensaid, Benoît; Eriksson, Klara Kristin; Mosnier, Amandine; Albert, Floriane; Mutez, Virginie; Brassard, Océane; Baysal, Tugba; Tardieu, Mathilde; Allatif, Omran; Fusil, Floriane; Andrieu, Thibault; Jullien, Denis; Dubois, Valérie; Giannoli, Catherine; Gruffat, Henri; Pallardy, Marc; Cosset, François-Loïc; Nosbaum, Audrey; ... (2021). Massive clonal expansion of polycytotoxic skin and blood CD8+ T cells in patients with toxic epidermal necrolysis. Science Advances, 7(12) American Association for the Advancement of Science 10.1126/sciadv.abe0013
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Toxic epidermal necrolysis (TEN) is a life-threatening cutaneous adverse drug reaction. To better understand why skin symptoms are so severe, we conducted a prospective immunophenotyping study on skin and blood. Mass cytometry results confirmed that effector memory polycytotoxic CD8+ T cells (CTLs) are the main leucocytes in TEN blisters at the acute phase. Deep T cell receptor (TCR) repertoire sequencing identified massive expansion of unique CDR3 clonotypes in blister cells. The same clones were highly expanded in patient's blood, and the degree of their expansion showed significant correlation with disease severity. By transducing α and β chains of the expanded clonotypes into a TCR-defective cell line, we confirmed that those cells were drug specific. Collectively, these results suggest that the relative clonal expansion and phenotype of skin-recruited CTLs condition the clinical presentation of cutaneous adverse drug reactions.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie 04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology and Immunology |
UniBE Contributor: |
Eriksson, Klara Kristin, Yerly, Daniel |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2375-2548 |
Publisher: |
American Association for the Advancement of Science |
Language: |
English |
Submitter: |
Lee-Anne Brand |
Date Deposited: |
21 Dec 2021 14:56 |
Last Modified: |
14 Aug 2023 08:06 |
Publisher DOI: |
10.1126/sciadv.abe0013 |
PubMed ID: |
33741590 |
BORIS DOI: |
10.48350/162403 |
URI: |
https://boris.unibe.ch/id/eprint/162403 |
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