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The Roles of Immunoregulatory Networks in Severe Drug Hypersensitivity.

Abstract
The immunomodulatory effects of regulatory T cells (Tregs) and co-signaling receptors have gained much attention, as they help balance immunogenic and immunotolerant responses that may be disrupted in autoimmune and infectious diseases. Drug hypersensitivity has a myriad of manifestations, which ranges from the mild maculopapular exanthema to the severe Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS). While studies have identified high-risk human leukocyte antigen (HLA) allotypes, the presence of the HLA allotype at risk is not sufficient to elicit drug hypersensitivity. Recent studies have suggested that insufficient regulation by Tregs may play a role in severe hypersensitivity reactions. Furthermore, immune checkpoint inhibitors, such as anti-CTLA-4 or anti-PD-1, in cancer treatment also induce hypersensitivity reactions including SJS/TEN and DRESS/DIHS. Taken together, mechanisms involving both Tregs as well as coinhibitory and costimulatory receptors may be crucial in the pathogenesis of drug hypersensitivity. In this review, we summarize the currently implicated roles of co-signaling receptors and Tregs in delayed-type drug hypersensitivity in the hope of identifying potential pharmacologic targets.
AuthorsYun-Shiuan Olivia Hsu, Kun-Lin Lu, Yun Fu, Chuang-Wei Wang, Chun-Wei Lu, Yu-Fen Lin, Wen-Cheng Chang, Kun-Yun Yeh, Shuen-Iu Hung, Wen-Hung Chung, Chun-Bing Chen
JournalFrontiers in immunology (Front Immunol) Vol. 12 Pg. 597761 ( 2021) ISSN: 1664-3224 [Electronic] Switzerland
PMID33717075 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
CopyrightCopyright © 2021 Hsu, Lu, Fu, Wang, Lu, Lin, Chang, Yeh, Hung, Chung and Chen.
Chemical References
  • Biomarkers
  • Costimulatory and Inhibitory T-Cell Receptors
  • Cytokines
Topics
  • Animals
  • Biomarkers
  • Costimulatory and Inhibitory T-Cell Receptors (metabolism)
  • Cytokines (metabolism)
  • Diagnosis, Differential
  • Disease Susceptibility (immunology)
  • Drug Hypersensitivity (diagnosis, etiology)
  • Gene Expression Regulation
  • Humans
  • Immunomodulation
  • Severity of Illness Index
  • Signal Transduction
  • T-Lymphocyte Subsets (immunology, metabolism)

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