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

Wuillemin, Natascha Andrea; Ballmer-Weber, Barbara; Schlapbach, Christoph; Jörg, Lukas; Yerly, Daniel (2022). The Activation Pattern of Drug-Reacting T Cells Has an Impact on the Clinical Picture of Hypersensitivity Reactions. Frontiers in allergy, 3, p. 804605. Frontiers Media S.A. 10.3389/falgy.2022.804605

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology and Immunology
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology

UniBE Contributor:

Wuillemin, Natascha Andrea, Schlapbach, Christoph, Jörg, Lukas, Yerly, Daniel

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2673-6101

Publisher:

Frontiers Media S.A.

Language:

English

Submitter:

Heidi Lobsiger

Date Deposited:

31 May 2022 15:37

Last Modified:

05 Dec 2022 16:20

Publisher DOI:

10.3389/falgy.2022.804605

PubMed ID:

35386648

Uncontrolled 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

BORIS DOI:

10.48350/170235

URI:

https://boris.unibe.ch/id/eprint/170235

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