Evolving models of the immunopathogenesis of T cell-mediated drug allergy: The role of host, pathogens, and drug response

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:136

Article

White, Katie D.¹  Chung, Wen-Hung^2,3,4  Hung, Shuen-Iu⁵  Mallal, Simon^1,6  Phillips, Elizabeth J.^1,6 

[1] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA

[2] Chang Gung Mem Hosp, Dept Dermatol, Keelung, Taiwan

[3] Chang Gung Mem Hosp, Drug Hypersensit Clin & Res Ctr, Dept Dermatol, Linkou, Taiwan

[4] Chang Gung Univ, Coll Med, Taoyuan, Taiwan

[5] Natl Yang Ming Univ, Program Mol Med, Inst Pharmacol, Sch Med,Infect & Immun Res Ctr, Taipei 112, Taiwan

[6] Murdoch Univ, Inst Immunol & Infect Dis, Murdoch, WA 6150, Australia

关键词: Abacavir;    adverse drug reaction;    allopurinol;    altered peptide;    carbamazepine;    drug reaction with eosinophilia and systemic symptoms;    hapten;    heterologous immunity;    human herpesvirus;    human leukocyte antigen;    major histocompatibility complex;    p-i;    pharmacogenetics;    pharmacogenomics;    Stevens-Johnson syndrome;    T-cell receptor;    toxic epidermal necrolysis;   

DOI  :  10.1016/j.jaci.2015.05.050

来源: Elsevier

【 摘 要 】

Immune-mediated (IM) adverse drug reactions (ADRs) are an underrecognized source of preventable morbidity, mortality, and cost. Increasingly, genetic variation in the HLA loci is associated with risk of severe reactions, highlighting the importance of T-cell immune responses in the mechanisms of both B cell-mediated and primary T cell-mediated IM-ADRs. In this review we summarize the role of host genetics, microbes, and drugs in IM-ADR development; expand on the existing models of IM-ADR pathogenesis to address multiple unexplained observations; discuss the implications of this work in clinical practice today; and describe future applications for preclinical drug toxicity screening, drug design, and development.

【 授权许可】

Free