HLA transgenic mice: application in reproducing idiosyncratic drug toxicity

Published on Aug 27, 2020in Drug Metabolism Reviews3.956
· DOI :10.1080/03602532.2020.1800725
Takeshi Susukida5
Estimated H-index: 5
(University of Toyama),
Shigeki Aoki7
Estimated H-index: 7
(Chiba University)
+ 3 AuthorsKousei Ito29
Estimated H-index: 29
(Chiba University)
Source
Abstract
Various types of transgenic mice carrying either class I or II human leukocyte antigen (HLA) molecules are readily available, and reports describing their use in a variety of studies have been publ...
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The interaction of human leukocyte antigen (HLA) with specific drugs is associated with delayed-type hypersensitivity reactions, which cause severe cutaneous toxicity. Such interactions induce structural alterations in HLA complexes via several different mechanisms such as the hapten theory, p-i concept, and altered peptide repertoire model, leading to the activation of cytotoxic T cells. To date, comprehensive detection of such structural alterations in preclinical studies has been difficult. H...
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Abstract Abacavir hypersensitivity syndrome (ABC HSS) is strongly associated with carriage of human leukocyte antigen (HLA)-B*57:01, which has a 100% negative predictive value for the development of ABC HSS. However, 45% of individuals who carry HLA-B*57:01 can tolerate ABC. We investigated immune and non-immune related genes in ABC HSS (n = 95) and ABC tolerant (n = 43) HLA-B*57:01 + patients to determine other factors required for the development of ABC HSS. Assignment of phenotype showed that...
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BACKGROUND: Abacavir is associated with hypersensitivity reactions in individuals positive for the HLA-B*57:01 allele. The drug binds within the peptide binding groove of HLA-B*57:01 altering peptides displayed on the cell surface. Presentation of these HLA-abacavir-peptide complexes to T-cells is hypothesized to trigger a CD8(+) T-cell response underpinning the hypersensitivity. Thus, the aim of this study was to explore the relationship between the structure of abacavir with HLA-B*57:01 bindin...
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#1Takeshi Susukida (University of Toyama)H-Index: 5
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Idiosyncratic drug toxicity (IDT) associated with specific human leukocyte antigen (HLA) allotype is a rare and unpredictable life-threatening adverse drug reaction for which prospective mechanistic studies in humans are difficult. Here, we show the importance of immune tolerance for IDT onset and determine whether it is susceptible to a common IDT, HLA-B*57:01-mediated abacavir (ABC)-induced hypersensitivity (AHS), using CD4+ T cell-depleted programmed death-1 receptor (PD-1)-deficient HLA-B*57...
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INTRODUCTION The licensed seasonal influenza vaccines predominantly induce neutralizing antibodies against immunodominant hypervariable epitopes of viral surface proteins, with limited protection against antigenically distant influenza viruses. Strategies have been developed to improve vaccines' performance in terms of broadly reactive and long-lasting immune response induction. AREAS COVERED We have summarized the advancements in the development of cross-protective influenza vaccines and discus...
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