Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Villani AP

PROVIDER: S-EPMC7978430 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Villani Axel Patrice AP Rozieres Aurore A Bensaid Benoît B Eriksson Klara Kristin KK Mosnier Amandine A Albert Floriane F Mutez Virginie V Brassard Océane O Baysal Tugba T Tardieu Mathilde M Allatif Omran O Fusil Floriane F Andrieu Thibault T Jullien Denis D Dubois Valérie V Giannoli Catherine C Gruffat Henri H Pallardy Marc M Cosset François-Loïc FL Nosbaum Audrey A Kanagawa Osami O Maryanski Janet L JL Yerly Daniel D Nicolas Jean-François JF Vocanson Marc M

Science advances 20210319 12

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<sup>+</sup> 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 sam ...[more]

PMID: 33741590

Similar Datasets

Project description:BackgroundStevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two of the most severe dermatologic emergencies. Although pregnant women comprise a subset of individuals at risk for SJS and TEN development, little is known with regard to outcomes and treatment.ObjectiveThis study aimed to conduct a systematic review to characterize the risk factors, outcomes, and treatment of SJS and TEN in pregnant patients and newborns.MethodsA primary literature search was conducted using PubMed in September 2019, using the following search terms entered in separate pairs: pregnant or pregnancy and stevens-johnson or SJS or toxic epidermal necrolysis. Reviews, studies in a language other than English, and articles not including pregnant patients were excluded.ResultsTwenty-six articles were included for review, including a total of 177 patients. The average maternal age for a reaction was 29.9 years, gestational age was 24.9 weeks, and time to reaction after drug initiation was 27.5 days. Approximately 85% of pregnant women in this review were infected with HIV. The most common causative medications were antiretroviral therapy (90% of all cases), antibiotics (3%), and gestational drugs (2%). Of the 94 cases in which outcome data were available, the survival rates of pregnant women and newborns after delivery were 98% and 96%, respectively. Withdrawal of the offending agent and supportive care was often sufficient for treatment, but antibiotics, steroids, and intravenous immunoglobulin were implemented in some cases. Complications included preterm labor, vaginal stenosis, and vaginal adhesions.ConclusionGiven the predominance of studies focusing on the subset of pregnant patients who are infected with HIV, SJS and TEN is most commonly reported in young patients after antiretroviral therapy, primarily nevirapine. Overall mortality is lower than that of the general population, but similar to the expected mortality rates of younger adults. Early recognition and withdrawal of the offending agent is essential to mitigate the distinct consequences of these conditions in the pregnant population.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets