Research Topic

The Immunology of Adverse Drug Reactions

About this Research Topic

Adverse reactions to therapeutic drugs represent a significant problem for patient care. Whilst most reactions can be explained by the drug pharmacology and are termed “predictable”, a subset of reactions are “idiosyncratic”, often mediated by inappropriate activation of the immune system. These reactions ...

Adverse reactions to therapeutic drugs represent a significant problem for patient care. Whilst most reactions can be explained by the drug pharmacology and are termed “predictable”, a subset of reactions are “idiosyncratic”, often mediated by inappropriate activation of the immune system. These reactions complicate the use of a wide range of therapeutics including anti-epileptic drugs (e.g. carbamazepine, phenytoin), antimicrobials (e.g. penicillins, sulphonamides, tuberculosis therapies), antivirals (e.g. abacavir, nevirapine), peri-operative agents and non-steroidal anti-inflammatory drugs (NSAIDs). Diverse pathologies of idiosyncratic adverse drug reactions exist, including both mild and severe cutaneous adverse drug reactions (CADRs), drug-induced liver injury (DILI), blood disorders, anaphylaxis and systemic syndromes (e.g. drug reaction with eosinophilia and systemic symptoms [DRESS]), which involve multiple organs. The immune mediators implicated in these reactions are equally diverse, with different ADRs reported to involve both innate immunity such as mast cells, eosinophils, macrophages, and natural killer cells, as well as adaptive components of the immune system such as B cells/immunoglobulins and T cells.

Understanding the etiology of these reactions has received intense scrutiny over the last few decades, with the ultimate goal of predicting and preventing the “unpredictable”. Investigations of the genetic correlates of risk have revealed associations of certain adverse drug reactions (ADRs) with specific alleles of the Human Leukocyte Antigen (HLA) genes. Indeed, in vitro explorations of T cell-mediated ADR have implicated drug-HLA interactions in the inappropriate activation of T cell responses against healthy tissues. Whilst some of these interactions appear highly allele-specific (e.g. abacavir and HLA-B*57:01, allopurinol and HLA-B*58:01), allowing prevention via screening for the culprit HLA, others are much more promiscuous (e.g. penicillins). Furthermore, drugs such as penicillins can trigger multiple immunopathologies via activation of IgE/mast cells and/or T cells. Even the strongest ADR risk biomarkers do not show 100% predictive accuracy and fail to explain why certain individuals experience a specific ADR, whilst others do not. The question therefore arises, what is necessary for a given drug to i) interact with immune receptors, and ii) break tolerance? Together with emerging animal models, cellular and biochemical assays have characterized the immunological pathway to specific ADRs, such as abacavir hypersensitivity syndrome, but we are still far from understanding the immunopathological mechanisms underpinning these debilitating reactions.

In this Research Topic, we aim to present a collection of immune-mediated ADR studies that incorporates Original Research articles, Methods, Mini Reviews, and Case Reports. Topics of particular interest include, but are not limited to:

· Immune pathology of idiosyncratic ADRs including cell types and mediators
· Mechanisms of tolerance
· Genomic and other risk factors for immune-mediated ADRs
· Novel immunological assays for ADR diagnosis/characterization
· Molecular interactions of therapeutics with immune receptors and immune pathways
· Immunology of drug hypersensitivity in cystic fibrosis
· Application of novel technologies (e.g. single-cell analysis) to understanding immune-mediated ADRs
· Animal models of ADRs


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Submission Deadlines

15 November 2020 Manuscript
28 February 2021 Manuscript Extension

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

15 November 2020 Manuscript
28 February 2021 Manuscript Extension

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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