The Activation Pattern of Drug-Reacting T Cells Has an Impact on the Clinical Picture of Hypersensitivity Reactions.

Natascha Wuillemin,Lukas Jörg,Barbara Ballmer-Weber,Christoph Schlapbach,Daniel Yerly

doi:10.3389/falgy.2022.804605

Natascha Wuillemin, Lukas Jörg + Show 3 more

Open Access

https://doi.org/10.3389/falgy.2022.804605

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Abstract

Rationaleβ-lactam antibiotics cause drug hypersensitivity reactions (DHR) with various clinical pictures from minor affections like maculopapular exanthema (MPE) and urticaria to severe cutaneous adverse reactions and anaphylaxis. Currently, two different reactivity patterns have been shown to initiate an immune reaction by activating T cells—the hapten concept and the pharmacological interaction with immune receptor (p–i) concept.ObjectivesIn this study, the relationship between the reactivity pattern of drug-reacting T cells of drug allergic patients and their clinical picture has been investigated.FindingsDrug-reacting T-cell clones (TCCs) were isolated from patients hypersensitive to β-lactams. Analysis of their reactivity pattern revealed an exclusive use of the hapten mechanism for patients with immediate reactions and for patients of MPE. In patients suffering from drug reactions with eosinophils and systemic symptoms, a severe DHR, analysis of isolated drug-reacting TCC identified the p–i concept as the unique mechanism for T-cell activation.ConclusionsThe results show a shift from hapten pattern in mild allergic reactions to p–i pattern in severe life-threatening allergic reactions. They strongly argue against the current preclinical risk evaluation of new drugs based on the ability to form haptens.

Highlights

Adverse drug reactions are a major cause of morbidity and mortality worldwide
Patients with immediate type allergy were included if they presented a positive prick test, and patients with delayed-type allergy were included if they presented a patch test and/or a positive lymphocyte transformation test (LTT) to the β-lactam
They were categorized into 4 groups: (A) patients with immediate-type hypersensitivity reaction with symptoms as urticaria or anaphylaxis, (B) patients with delayedtype reaction with maculopapular exanthema (MPE), clinically diagnosed as an erythematous skin eruption with papules without signs of blistering, pustules, mucosal, or systemic involvement, (C) patients with drug reaction with eosinophils and systemic symptoms (DRESS), and (D) patients with Stevens Johnson syndrome (SJS) (Table 1)

Summary

Introduction

Up to 30% of these adverse reactions are attributable to drug hypersensitivity reactions (DHRs). Most of these DHRs are mediated by the adaptive immune system and the severity of the symptoms extends from mild to life-threatening reactions. For delayed type DHR, drug-reacting T cells are thought to be the key player. Such T cells were observed in the skin lesions of drug-induced maculopapular exanthema (MPE) [2], in the blisters of severe Stevens Johnson syndrome (SJS) [3], and in internal organ lesions of drug reaction with eosinophils and systemic symptoms (DRESS) [4].

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