The important role of non-covalent drug-protein interactions in drug hypersensitivity reactions.
allo-immunity
drug hypersensitivity
fake antigen
heterologous immunity
virus reactivation
Journal
Allergy
ISSN: 1398-9995
Titre abrégé: Allergy
Pays: Denmark
ID NLM: 7804028
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
revised:
14
05
2021
received:
11
03
2021
accepted:
20
05
2021
pubmed:
27
5
2021
medline:
9
4
2022
entrez:
26
5
2021
Statut:
ppublish
Résumé
Drug hypersensitivity reactions (DHR) are heterogeneous and unusual immune reactions with rather unique clinical presentations. Accumulating evidence indicates that certain non-covalent drug-protein interactions are able to elicit exclusively effector functions of antibody reactions or complete T-cell reactions which contribute substantially to DHR. Here, we discuss three key interactions; (a) mimicry: whereby soluble, non-covalent drug-protein complexes ("fake antigens") mimic covalent drug-protein adducts; (b) increased antibody affinity: for example, in quinine-type immune thrombocytopenia where the drug gets trapped between antibody and membrane-bound glycoprotein; and (c) p-i-stimulation: where naïve and memory T cells are activated by direct binding of drugs to the human leukocyte antigen and/or T-cell receptors. This transient drug-immune receptor interaction initiates a polyclonal T-cell response with mild-to-severe DHR symptoms. Notable complications arising from p-i DHR can include viral reactivations, autoimmunity, and multiple drug hypersensitivity. In conclusion, DHR is characterized by abnormal immune stimulation driven by non-covalent drug-protein interactions. This contrasts DHR from "normal" immunity, which relies on antigen-formation by covalent hapten-protein adducts and predominantly results in asymptomatic immunity.
Identifiants
pubmed: 34037262
doi: 10.1111/all.14962
pmc: PMC9291849
doi:
Substances chimiques
HLA Antigens
0
Haptens
0
Receptors, Antigen, T-Cell
0
Receptors, Immunologic
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
404-415Informations de copyright
© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
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