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

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

doi:10.3389/falgy.2022.804605

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

Front Allergy. 2022 Feb 21:3:804605. doi: 10.3389/falgy.2022.804605. eCollection 2022.

Authors

Natascha Wuillemin¹, Barbara Ballmer-Weber², Christoph Schlapbach³, Lukas Jörg⁴, Daniel Yerly¹

Affiliations

¹ Department of Rheumatology, Immunology and Allergology, University Hospital of Bern, Bern, Switzerland.
² Clinic for Dermatology and Allergology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
³ Department of Dermatology, University Hospital of Bern, Bern, Switzerland.
⁴ Policlinic for Allergology and Clinical Immunology, University Clinic for Pneumology, University Hospital of Bern, Bern, Switzerland.

Abstract

Rationale: β-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.

Objectives: In this study, the relationship between the reactivity pattern of drug-reacting T cells of drug allergic patients and their clinical picture has been investigated.

Findings: Drug-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.

Conclusions: The 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.

Keywords: T cells; drug allergy; drug reaction with eosinophilia and systemic symptoms (DRESS); hapten concept; maculopapular drug eruption; p–i-concept; severe cutaneous adverse drug reaction.