The Roles of Immunoregulatory Networks in Severe Drug Hypersensitivity

Hsu, Yun‐Shiuan Olivia; Lu, Kun-Lin; Fu, Yao‐Shi; Wang, Chuang‐Wei; Lu, Chun‐Wei; Lin, Yu-Fen; Chang, Wen‐Cheng; Yeh, Kun‐Yun; Hung, Shuen‐Iu; Chung, Wen‐Hung; Chen, Chun‐Bing

doi:10.3389/fimmu.2021.597761

Cited by 22 publications

(16 citation statements)

References 238 publications

(274 reference statements)

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“…Insufficient regulation by regulatory T cells (Tregs) may play a role in severe hypersensitivity reactions. Immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1) in cancer treatment may also induce SJS/TEN and DRESS/DIHS and other hypersensitivity reactions [201].…”

Section: Immunopharmacogenomics and Cutaneous Adrsmentioning

confidence: 99%

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Cacabelos

Naidoo

Corzo

et al. 2021

IJMS

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Adverse drug reactions (ADRs) rank as one of the top 10 leading causes of death and illness in developed countries. ADRs show differential features depending upon genotype, age, sex, race, pathology, drug category, route of administration, and drug–drug interactions. Pharmacogenomics (PGx) provides the physician effective clues for optimizing drug efficacy and safety in major problems of health such as cardiovascular disease and associated disorders, cancer and brain disorders. Important aspects to be considered are also the impact of immunopharmacogenomics in cutaneous ADRs as well as the influence of genomic factors associated with COVID-19 and vaccination strategies. Major limitations for the routine use of PGx procedures for ADRs prevention are the lack of education and training in physicians and pharmacists, poor characterization of drug-related PGx, unspecific biomarkers of drug efficacy and toxicity, cost-effectiveness, administrative problems in health organizations, and insufficient regulation for the generalized use of PGx in the clinical setting. The implementation of PGx requires: (i) education of physicians and all other parties involved in the use and benefits of PGx; (ii) prospective studies to demonstrate the benefits of PGx genotyping; (iii) standardization of PGx procedures and development of clinical guidelines; (iv) NGS and microarrays to cover genes with high PGx potential; and (v) new regulations for PGx-related drug development and PGx drug labelling.

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Section: Immunopharmacogenomics and Cutaneous Adrsmentioning

confidence: 99%

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Cacabelos

Naidoo

Corzo

et al. 2021

IJMS

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“…The drug triggering SJS binds the T cell receptor and MHC class I, and as a result, it leads to the massive replication of cytotoxic T cells, which directly kill keratinocytes, and the release of granulysin, which destroys cells in the skin and the mucous membrane[ 20 ]. Yun-Shiuan’s research showed that the blockade of PD-1/PD-L1 may contribute to the imbalance of the immune system, manifesting the enhancement of the T cell response and increasing the incidence of hypersensitivity[ 21 ]. During the treatment of SJS induced by ipilimumab and nivolumab in a melanoma patient[ 22 ], an increase in CD8+ T cells in the dermal epidermal junction and an increase in PD-L1 expression in keratinocytes were noted.…”

Section: Discussionmentioning

confidence: 99%

Pembrolizumab-induced Stevens-Johnson syndrome in advanced squamous cell carcinoma of the lung: A case report and review of literature

Wu¹,

Kang²,

Yi³

et al. 2022

WJCC

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BACKGROUND For advanced lung squamous cell carcinoma, immune checkpoint inhibitors (ICIs) have been regarded as one of the optimal therapies. While immune-related adverse events (irAEs) are common in ICI treatment, cutaneous toxicities are among the most common irAEs. Most immune-related skin toxicity grades are low, and the prognosis is good. However, Stevens-Johnson syndrome (SJS) is a rare but extremely severe cutaneous adverse drug reaction with high mortality. CASE SUMMARY We report a rare case of SJS induced by pembrolizumab. The case involved a 68-year-old female who was diagnosed with advanced squamous cell carcinoma of the lung. SJS appeared after one cycle of immunotherapy combined with chemotherapy. After treatment with prednisone hormone symptoms, anti-infection, gamma globulin, and antipruritic agents, the skin toxicity of the patients gradually decreased and eventually disappeared. Although the antitumor treatment was stopped due to serious adverse reactions, the tumor of the patient remained stable for nearly half a year after one cycle of immune therapy combined with chemotherapy, which also corroborates the delayed effect of immunotherapy. CONCLUSION We believe our report can provide some references for the treatment of SJS and the treatment of immune-related adverse reactions.

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“…The field of immune checkpoint inhibition represents an exciting prospect for targeted enhancement of T-cell antigenicity, particularly in cancer therapy [55], whereas dysregulation of this system may impact on susceptibility to drug hypersensitivity. This is because the same mechanism that is known to enhance tumorigenic T-cell activity, unfortunately may result in uncontrolled T-cell activation leading to a barrage of autoimmune and drug hypersensitivity events [56,57 ▪▪ ]. One such drug example is with the radio contrast media amidotrizoate, where a patient received multiple doses without issue; however, concomitant administration of the PD-L1 blocker atezolizumab resulted in severe hypersensitivity manifestations [57 ▪▪ ].…”

Section: Signal 2 and Immune Dysregulationmentioning

confidence: 99%

Pathology of T-cell-mediated drug hypersensitivity reactions and impact of tolerance mechanisms on patient susceptibility

Line

Thomson

Naisbitt

2022

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of reviewT-cell-mediated drug hypersensitivity is responsible for significant morbidity and mortality, and represents a substantial clinical concern. The purpose of this article is to focus on T-cell reactions and discuss recent advances in disease pathogenesis by exploring the impact of tolerance mechanisms in determining susceptibility in genetically predisposed patients. Recent findingsCertain drugs preferentially activate pathogenic T cells that have defined pathways of effector function. Thus, a critical question is what extenuating factors influence the direction of immune activation. A large effort has been given towards identifying phenotypic (e.g., infection) or genotypic (e.g., human leukocyte antigen) associations which predispose individuals to drug hypersensitivity. However, many individuals expressing known risk factors safely tolerate drug administration. Thus, mechanistic insight is needed to determine what confers this tolerance. Herein, we discuss recent clinical/mechanistic findings which indicate that the direction in which the immune system is driven relies upon a complex interplay between co-stimulatory/co-regulatory pathways which themselves depend upon environmental inputs from the innate immune system.

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The Roles of Immunoregulatory Networks in Severe Drug Hypersensitivity

Cited by 22 publications

References 238 publications

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Pembrolizumab-induced Stevens-Johnson syndrome in advanced squamous cell carcinoma of the lung: A case report and review of literature

Pathology of T-cell-mediated drug hypersensitivity reactions and impact of tolerance mechanisms on patient susceptibility

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