RT Journal Article
T1 Delayed reactions to drugs show levels of perforin, granzyme B, and Fas-L to be related to disease severity.
A1 Posadas, Sinforiano Jose
A1 Padial, Antonia
A1 Torres-Jaén, María Josefa
A1 Mayorga Mayorga, Cristobalina
A1 Leyva-Fernández, Laura
A1 Sánchez, Elena
A1 Álvarez, Javier
A1 Romano, Antonino
A1 Juárez, Carlos
A1 Blanca, Miguel
A1 Sánchez, Elena
K1 Alergia a los medicamentos
K1 Dermatitis medicamentosa
AB Background Drugs can induce different immunologic reactions; T-cell mediated responses produce the most severe reactions. Although in vitro studies show that T cells recognize drugs or their metabolites and induce an effector cytotoxic response, direct in vivo evidence of involvement is lacking. T lymphocytes produce cytotoxic markers that are responsible for 2 major pathways to cell death: granule-mediated exocytosis (perforin and granzyme B) and Fas/FasL interaction.Objective: The purpose of this investigation was to establish the role of proinflammatory TNF-α and cytotoxic markers in subjects with delayed responses to drugs.Methods: We assessed expression levels by quantitative-competitive PCR of TNF-α, perforin, granzyme B, and FasL in mononuclear cells from peripheral blood and blister fluid from subjects with delayed reactions to drugs. Samples were obtained within 24 hours of the reaction and 30 days later. Fifteen patients were included and classified according to severity of the reaction, as follows: (A) maculopapular exanthema, (B)desquamative exanthema, (C) Stevens-Johnson syndrome, (D) toxic epidermal necrolysis.Results: At the acute stage, there was a large increase in TNF-α (9-fold), perforin (6-fold), and GrB (7-fold) in patients in comparison with control subjects. FasL was expressed in PBMCs only in Stevens-Johnson syndrome and toxic epidermal necrolysis. A high association between cytotoxic markers and disease severity was seen (P < .001).Conclusions. Our data show that TNF-α, perforin, GrB, and FasL are increased in the early stage of disease, suggesting that a cytotoxic mechanism might be taking part. These findings support the role of T cells in allergic drug reactions and provide further clues pertaining to therapeutic interventions.
PB Elsevier
YR 2002
FD 2002
LK https://hdl.handle.net/10630/32580
UL https://hdl.handle.net/10630/32580
LA eng
NO Posadas SJ, Padial A, Torres MJ, Mayorga C, Leyva L, Sanchez E, Alvarez J, Romano A, Juarez C, Blanca M. Delayed reactions to drugs show levels of perforin, granzyme B, and Fas-L to be related to disease severity. J Allergy Clin Immunol. 2002 Jan;109(1):155-61. PMID:11799383
NO Política de acceso abierto tomada de:https://v2.sherpa.ac.uk/id/publication/3193
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 3 mar 2026