Advances in the Pathomechanisms of Delayed Drug Hypersensitivity

Chuang-Wei Wang; Sherrie Jill Divito; Wen-Hung Chung; Shuen-Iu Hung

doi:10.1016/j.iac.2022.01.002

Advances in the Pathomechanisms of Delayed Drug Hypersensitivity

Immunol Allergy Clin North Am. 2022 May;42(2):357-373. doi: 10.1016/j.iac.2022.01.002. Epub 2022 Mar 31.

Authors

Chuang-Wei Wang¹, Sherrie Jill Divito², Wen-Hung Chung³, Shuen-Iu Hung⁴

Affiliations

¹ Cancer Vaccine & Immune Cell Therapy Core Lab, Department of Medical Research, Chang Gung Memorial Hospital, Linkou Branch, No. 5, Fuxing St., Guishan Dist., Taoyuan 333, Taiwan; Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou Branch, No. 5, Fuxing St., Guishan Dist., Taoyuan 333, Taiwan; Department of Dermatology, Xiamen Chang Gung Hospital, No. 123, Xiafei Road, Haicang District, Xiamen, China.
² Department of Dermatology, Brigham & Women's Hospital, Harvard Medical School, 221 Longwood Avenue, EBRC Room 513, Boston, MA 02115, USA.
³ Cancer Vaccine & Immune Cell Therapy Core Lab, Department of Medical Research, Chang Gung Memorial Hospital, Linkou Branch, No. 5, Fuxing St., Guishan Dist., Taoyuan 333, Taiwan; Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou Branch, No. 5, Fuxing St., Guishan Dist., Taoyuan 333, Taiwan; Department of Dermatology, Xiamen Chang Gung Hospital, No. 123, Xiafei Road, Haicang District, Xiamen, China; Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung Branch, No. 222, Maijin Rd., Anle Dist., Keelung 204, Taiwan; College of Medicine, Chang Gung University, No.259, Wenhua 1st Rd., Guishan Dist., Taoyuan 333, Taiwan. Electronic address: chung1@cgmh.org.tw.
⁴ Cancer Vaccine & Immune Cell Therapy Core Lab, Department of Medical Research, Chang Gung Memorial Hospital, Linkou Branch, No. 5, Fuxing St., Guishan Dist., Taoyuan 333, Taiwan; Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou Branch, No. 5, Fuxing St., Guishan Dist., Taoyuan 333, Taiwan; Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, No.155, Sec.2, Linong Street, Taipei, 112 Taiwan. Electronic address: sihung@cgmh.org.tw.

PMID: 35469623
DOI: 10.1016/j.iac.2022.01.002

Abstract

Delayed drug hypersensitivity continues to contribute to major clinical problems worldwide. The clinical presentations of delayed drug hypersensitivity are diverse, ranging from mild skin rashes to life-threatening systemic reactions. The pathomechanism of delayed drug hypersensitivity involves human leukocyte antigens (HLA) presentation of drugs/metabolites to T cell receptors (TCR), resulting in T-cell activation. The pathogenesis of delayed drug hypersensitivity also has reactivation of the virus, and activation of many immune mediators. In this review, we discuss the immune pathogenesis, molecular interactions of HLA/drugs/TCR, and downstream signaling of cytotoxic proteins/cytokines/chemokines, as well as disease prevention and management for delayed drug hypersensitivity.

Keywords: Cytotoxic proteins; Delayed drug hypersensitivity; Human leukocyte antigens; Immune checkpoint blockade; Severe cutaneous adverse reactions; T cell receptor.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Drug Hypersensitivity* / diagnosis
Drug Hypersensitivity* / therapy
HLA Antigens / genetics
Humans
Receptors, Antigen, T-Cell / genetics

Substances

HLA Antigens
Receptors, Antigen, T-Cell

Abstract

Publication types

MeSH terms

Substances

Grants and funding