Basic and clinical immunologyToxic epidermal necrolysis: Effector cells are drug-specific cytotoxic T cells
Section snippets
Cells from patients
The study was performed on the blister fluid lymphocytes of patients hospitalized for TEN in a specialized unit. Among 25 consecutive patients with biopsy-proven TEN, we studied all 6 with enough blister fluid cells (n = 15), a single drug suspected as responsible (8/15), and availability of a soluble form of this drug (6/8). An ethical committee (Comité Consultatif pour la Protection des Personnes se prêtant à une Recherche Biomédicale Hôpital Pitié-Salpêtrière, Paris, France) approved the
Immunophenotype of blister fluid cells
Phenotypic analysis of T lymphocytes present in blister fluids from 6 patients with TEN is presented in Table I. The majority of the lymphocytes were CD3+T-cell receptor (TCR) αβ+, with a huge predominance of the CD8+ subset. In most patients, these lymphocytes were activated as they expressed HLA-DR and had been targeted to home in the skin because they were stained by anti–cutaneous lymphocyte-associated antigen (CLA) monoclonal antibody. In 5 of the 6 patients, there was a significant
Discussion
We had previously found CD8+ T lymphocytes exhibiting drug-specific cytotoxicity in the blister fluid of a single patient with TMP-SMX–related TEN.14 These specific CTLs were MHC class I–restricted and used a perforin/granzyme–mediated pathway to exert their killing.
The current data extend these initial findings in a total of 6 patients, demonstrate that the blister fluid cells can also kill autologous keratinocytes in the presence of the drug, and suggest cross-reactivity of
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Pathophysiology of cutaneous adverse reactions. Lyell's syndrome, a massive clonal expansion of polycytotoxic CD8+ T cells
2023, Bulletin de l'Academie Nationale de MedecineInhibition of tumor necrosis factor improves conventional steroid therapy for Stevens-Johnson syndrome/toxic epidermal necrolysis in a cohort of patients
2022, Journal of the American Academy of DermatologyCitation Excerpt :To our knowledge, this has not been investigated so far. The pathogenesis of SJS/TEN is generally considered to be a T-cell–mediated cytotoxic reaction that results in keratinocytes apoptosis and necrosis.10,11 In addition to cytotoxic mediators, such as granzyme B (GzmB) and granulysin, a broad spectrum of cytokines, including TNF-α, are also shown to be involved in SJS/TEN.10,12-16
Mycoplasma-induced Stevens-Johnson syndrome/toxic epidermal necrolysis: Case-control analysis of a cohort managed in a specialized center
2022, Journal of the American Academy of Dermatology
Supported in part by a grant from the French Ministry of Health (No AOM 98027) and through contracts between Institut National de la Santé Et de la Recherche Médicale and the following drug companies: Bayer, Glaxo-Wellcome, Hoechst-Marion-Roussel, Leo, Lilly, Novartis, Parke-Davis-Jouveinal, Pfizer, Rhone-Poulenc-Rorer, Sanofi-Winthrop, and Servier. Dr Nassif was the recipient of grants from Fondation pour la Recherche Médicale and Société pour l'Investigation Dermatologique Et Allergologique. Dr Moslehi received a grant from the Fondation René Touraine.