TY - JOUR
T1 - Advances in Our Understanding of the Interaction of Drugs with T-cells
T2 - Implications for the Discovery of Biomarkers in Severe Cutaneous Drug Reactions
AU - Hernandez-Jaimes, Olivia Araceli
AU - Cazares-Olvera, Diana Valeria
AU - Line, James
AU - Moreno-Eutimio, Mario Adan
AU - Gómez-Castro, Carlos Zepactonal
AU - Naisbitt, Dean J.
AU - Castrejón-Flores, José Luis
N1 - Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.
PY - 2022/7/18
Y1 - 2022/7/18
N2 - Drugs can activate different cells of the immune system and initiate an immune response that can lead to life-threatening diseases collectively known as severe cutaneous adverse reactions (SCARs). Antibiotics, anticonvulsants, and antiretrovirals are involved in the development of SCARs by the activation of αβ naïve T-cells. However, other subsets of lymphocytes known as nonconventional T-cells with a limited T-cell receptor repertoire and innate and adaptative functions also recognize drugs and drug-like molecules, but their role in the pathogenesis of SCARs has only just begun to be explored. Despite 30 years of advances in our understanding of the mechanisms in which drugs interact with T-cells and the pathways for tissue injury seen during T-cell activation, at present, the development of useful clinical biomarkers for SCARs or predictive preclinical in vitro assays that could identify immunogenic moieties during drug discovery is an unmet goal. Therefore, the present review focuses on (i) advances in the understanding of the pathogenesis of SCARs reactions, (ii) a description of the interaction of drugs with conventional and nonconventional T-cells, and (iii) the current state of soluble blood circulating biomarker candidates for SCARs.
AB - Drugs can activate different cells of the immune system and initiate an immune response that can lead to life-threatening diseases collectively known as severe cutaneous adverse reactions (SCARs). Antibiotics, anticonvulsants, and antiretrovirals are involved in the development of SCARs by the activation of αβ naïve T-cells. However, other subsets of lymphocytes known as nonconventional T-cells with a limited T-cell receptor repertoire and innate and adaptative functions also recognize drugs and drug-like molecules, but their role in the pathogenesis of SCARs has only just begun to be explored. Despite 30 years of advances in our understanding of the mechanisms in which drugs interact with T-cells and the pathways for tissue injury seen during T-cell activation, at present, the development of useful clinical biomarkers for SCARs or predictive preclinical in vitro assays that could identify immunogenic moieties during drug discovery is an unmet goal. Therefore, the present review focuses on (i) advances in the understanding of the pathogenesis of SCARs reactions, (ii) a description of the interaction of drugs with conventional and nonconventional T-cells, and (iii) the current state of soluble blood circulating biomarker candidates for SCARs.
UR - http://www.scopus.com/inward/record.url?scp=85134632037&partnerID=8YFLogxK
U2 - 10.1021/acs.chemrestox.1c00434
DO - 10.1021/acs.chemrestox.1c00434
M3 - Artículo de revisión
C2 - 35704769
AN - SCOPUS:85134632037
SN - 0893-228X
VL - 35
SP - 1162
EP - 1183
JO - Chemical Research in Toxicology
JF - Chemical Research in Toxicology
IS - 7
ER -