Mechanisms leading to T-cell activation in drug hypersensitivity

Meng, Xiaoli; Yerly, Daniel; Naisbitt, Dean J.

doi:10.1097/aci.0000000000000458

Cited by 26 publications

(28 citation statements)

References 45 publications

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“…CD154 is a member of the TNF‐superfamily and is expressed by CD8 +ve cytotoxic T cells, which can also be involved in NIDHRs, for example a maculopapular exanthema to β‐lactams. With respect to the application of a CD154‐based lymphocyte activation test (LAT) in NIDHRs, we located a single series of 14 patients .…”

Section: Figuresupporting

confidence: 82%

CD154 (CD40L): A novel aid to document nonimmediate hypersensitivity to amoxicillin or amoxicillin clavulanic acid

Gasse

Ebo

Mertens

et al. 2020

Clin Experimental Allergy

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Section: Figuresupporting

confidence: 82%

CD154 (CD40L): A novel aid to document nonimmediate hypersensitivity to amoxicillin or amoxicillin clavulanic acid

Gasse

Ebo

Mertens

et al. 2020

Clin Experimental Allergy

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“…This study focused on BP as a drug model since it has been associated with heterogeneous clinical allergic reactions, and it is known to bind covalently to selective lysine residues on proteins . According to the hapten hypothesis, adducts formed inside and outside of the antigen‐presenting cells usually undergo protein processing to generate MHC‐binding peptides that are assumed to contain the drug modification . Moreover, our group has previously showed the pre‐existence of a naïve CD4+ T cell repertoire for BP .…”

Section: Discussionmentioning

confidence: 99%

“…Protein haptenation by covalent conjugation of drugs such as benzylpenicillin (BP) is considered to be one of the key process for immunization and allergic reaction . Significant progress has been made in understanding the immunopathogenesis of allergic drug reactions, and drug‐specific memory T cells have been detected in drug allergic patients . However, little is known about the origin of patients’ immunization to drugs.…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of a naïve CD8+ T cell repertoire for benzylpenicillin

Bechara

Maillère

Joseph

et al. 2019

Clin Experimental Allergy

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Background: Beta-lactams allergy is the most commonly reported drug allergy and constitutes an important health problem. We previously showed the pre-existence of a naïve CD4+ T cell repertoire for benzylpenicillin (BP) coupled to human serum albumin (HSA) but little is known about the naïve CD8+ T cell repertoire specific for BP.Objective: The purpose of this work was to identify naïve CD8+ T cells specific for BP and to explore mechanisms dictating their activation.Methods: Co-cultures were established with naïve CD8+ T cells and autologous dendritic cells (DCs) loaded with HSA-BP or free BP. T cells were restimulated once a week with autologous DCs loaded with HSA-BP or BP. The specific CD8+ T cell response was measured using an IFN-γ ELISpot assay.Results: When using free BP, we were able to detect a naïve CD8+ T cell repertoire for BP in the 6 out of 7 tested healthy donors. However, our results showed that HSA-BP was recognized by naïve CD8+ T cells in only one donor out of five tested healthy donors. Using free BP, we evidenced its binding to cellular proteins in DCs that was concentration dependent and was correlated with BP-specific CD8+ T cell activation. Moreover, the BP-specific CD8+ cell response was MHC class I-dependent and required intracellular processing and proteasome activity. Conclusion and clinical relevance:This work showed the existence of a naïve CD8+ T cell repertoire for BP when DCs were treated with free BP suggesting that patients could be immunized by haptenated peptides from cellular proteins generated in antigen-presenting cells.

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“…p‐I reactions are considered NIR since symptoms appear only after specific T‐cell expansion and migration into tissue . Latest advances in their mechanisms have focused on finding new associations with specific HLA alleles . However, it is necessary to take into account that in antiretroviral drugs hypersensitivity, the virus peptides presented in the context of drug T‐cell stimulation can influence the reaction.…”

Section: New Understanding Of Dhr Mechanismmentioning

confidence: 99%

Recent developments and highlights in drug hypersensitivity

Mayorga

Fernandez

Montañez

et al. 2019

Allergy

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Drug hypersensitivity reactions (DHRs) are nowadays the third cause of allergy after rhinitis and asthma with a significant increase in prevalence in both adults and paediatric population with new drugs included as culprit. For this, DHRs represent not only a health problem but also a significant financial burden for affected individuals and health systems. Mislabelling DHRs is showing to be a relevant problem for both, false label of drug allergic and false label of nonallergic. All this reinforces the need to improve accurate diagnostic approaches that allow an appropriate management.Moreover, there is a need for training both, nonallergist stakeholders and patients to improve the reaction identification and therefore decrease the mislabelling. The use of allergy cards has shown to be relevant to avoid the induction of DHRs due to the prescription of wrong medication.Recent developments over the last 2 years and highlights about risk factors, diagnostic approaches, mechanisms involved as well as prevention actions, and management have been reviewed. In these papers, it has been outlined the need for correct diagnosis and de-labelling of patients previously false-reported as allergic, which will improve the management and treatment of patients with DHRs. K E Y W O R D Sallergy diagnosis, allergy treatment, basic mechanisms, drug allergy, epidemiology | 2369

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Mechanisms leading to T-cell activation in drug hypersensitivity

Cited by 26 publications

References 45 publications

CD154 (CD40L): A novel aid to document nonimmediate hypersensitivity to amoxicillin or amoxicillin clavulanic acid

CD154 (CD40L): A novel aid to document nonimmediate hypersensitivity to amoxicillin or amoxicillin clavulanic acid

Identification and characterization of a naïve CD8+ T cell repertoire for benzylpenicillin

Recent developments and highlights in drug hypersensitivity

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