title: Cytotoxic proteins and therapeutic targets in severe cutaneous adverse reactions.
abstract: Severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN), are rare but life-threatening conditions induced mainly by a variety of drugs. Until now, an effective treatment for SJS/TEN still remains unavailable. Current studies have suggested that the pathobiology of drug-mediated SJS and TEN involves major histocompatibility class (MHC) I-restricted activation of cytotoxic T lymphocytes (CTLs) response. This CTLs response requires several cytotoxic signals or mediators, including granulysin, perforin/granzyme B, and Fas/Fas ligand, to trigger extensive keratinocyte death. In this article, we will discuss the cytotoxic mechanisms of severe cutaneous adverse reactions and their potential applications on therapeutics for this disease.
authors.affiliation: Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospitals, Taipei, Linkou, and Keelung, 33305, Taiwan. zenith5862@hotmail.com.
authors.forename: Shih-Chi
authors.initials: SC
authors.lastname: Su
authors.affiliation: Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospitals, Taipei, Linkou, and Keelung, 33305, Taiwan. chung1@cgmh.org.tw.
authors.forename: Wen-Hung
authors.initials: WH
authors.lastname: Chung
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D064420:Drug-Related Side Effects and Adverse Reactions / Q000188:drug therapy*; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D053804:Granzymes / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D007694:Killer Cells, Natural / Q000378:metabolism; D008285:Major Histocompatibility Complex / Q000235:genetics; D054353:Perforin / Q000235:genetics / Q000378:metabolism; D013262:Stevens-Johnson Syndrome / Q000188:drug therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D053222:Fas Ligand Protein; C075005:GNLY protein, human; D054353:Perforin; D053804:Granzymes