Massive clonal expansion of polycytotoxic skin and blood CD8+ T cells in patients with toxic epidermal necrolysis.

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)

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, Clinical Immunology and Allergology

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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