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)
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...
📖 Papers frequently viewed together
1 Author (Terry Gordon)
15 Citations
#1Tomohiro Shirayanagi (Chiba University)H-Index: 1
#2Shigeki Aoki (Chiba University)H-Index: 7
Last. Kousei Ito (Chiba University)H-Index: 29
view all 9 authors...
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...
2 CitationsSource
#1Rebecca Pavlos (UWA: University of Western Australia)H-Index: 15
#2Pooja Deshpande (UWA: University of Western Australia)H-Index: 5
Last. Elizabeth J. Phillips (UWA: University of Western Australia)H-Index: 61
view all 20 authors...
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...
9 CitationsSource
#1Paul J. Thomson (University of Liverpool)H-Index: 8
#2Patricia T. Illing (Monash University, Clayton campus)H-Index: 16
Last. Dean J. Naisbitt (University of Liverpool)H-Index: 59
view all 10 authors...
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...
11 CitationsSource
#1Francesco Maurano (National Research Council)H-Index: 25
#2Tasuku Ogita (Shinshu University)H-Index: 9
Last. Mauro Rossi (National Research Council)H-Index: 61
view all 8 authors...
Abstract Celiac disease (CD) is a food enteropathy that occurs in genetically susceptible individuals following the ingestion of gluten. Both gluten cytotoxicity and immunity activation play a role in CD pathogenesis; however, the chronological assessment of the different pathogenic mechanisms remains elusive. The models developed so far have only partially addressed this issue. Herein, Ab°DQ8 transgenic mice were administered wheat gliadin and indomethacin for 10 days to induce enteropathy. Gli...
1 CitationsSource
#1Itay Raphael (University of Pittsburgh)H-Index: 7
#2Francisco Gomez-Rivera (UTSA: University of Texas at San Antonio)H-Index: 2
Last. Thomas G. Forsthuber (UTSA: University of Texas at San Antonio)H-Index: 32
view all 6 authors...
Multiple sclerosis (MS) is an autoimmune neuroinflammatory disease where the underlying mechanisms driving disease progression have remained unresolved. HLA-DR2b (DRB1*15:01) is the most common genetic risk factor for MS. Additionally, TNF and its receptors TNFR1 and TNFR2 play key roles in MS and its preclinical animal model, experimental autoimmune encephalomyelitis (EAE). TNFR2 is believed to ameliorate CNS pathology by promoting remyelination and Treg function. Here, we show that transgenic ...
5 CitationsSource
#1Ren-You Pan (Memorial Hospital of South Bend)H-Index: 6
#2Mu-Tzu Chu (NYMU: National Yang-Ming University)H-Index: 3
Last. Shuen-Iu Hung (NYMU: National Yang-Ming University)H-Index: 4
view all 18 authors...
Drug hypersensitivity such as severe cutaneous adverse reactions (SCAR), including Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), could be life-threatening. Here, we enroll SCAR patients to investigate the T cell receptor (TCR) repertoire by next-generation sequencing. A public αβTCR is identified from the cytotoxic T lymphocytes of patients with carbamazepine-SJS/TEN, with its expression showing drug/phenotype-specificity and an bias for HLA-B*15:02. This public αβTCR has ...
42 CitationsSource
#1Michal Pyzik (Brigham and Women's Hospital)H-Index: 15
#2Kine Marita Knudsen Sand (University of Oslo)H-Index: 9
Last. Richard S. Blumberg (Harvard University)H-Index: 111
view all 6 authors...
Antibodies are essential components of an adaptive immune response. Immunoglobulin G (IgG) is the most common type of antibody found in circulation and extracellular fluids. Although IgG alone can directly protect the body from infection through the activities of its antigen binding region, the majority of IgG immune functions are mediated via proteins and receptors expressed by specialized cell subsets that bind to the fragment crystallizable (Fc) region of IgG. Fc gamma () receptors (FcR) be...
117 CitationsSource
#1Shaikh M. Atif (Anschutz Medical Campus)H-Index: 16
#2Douglas G. Mack (Anschutz Medical Campus)H-Index: 29
Last. Andrew P. Fontenot (Anschutz Medical Campus)H-Index: 45
view all 10 authors...
: Susceptibility to chronic beryllium (Be) disease is linked to HLA-DP molecules possessing a glutamic acid at the 69th position of the β-chain (βGlu69), with the most prevalent βGlu69-containing molecule being HLA-DP2. We have previously shown that HLA-DP2 transgenic (Tg) mice exposed to Be oxide (BeO) develop mononuclear infiltrates in a peribronchovascular distribution and a beryllium-specific, HLA-DP2-restricted CD4+ T cell response. In addition to T cells, B cells constituted a major portio...
8 CitationsSource
#1Elizabeth T. Cirulli (Center for Applied Genomics)H-Index: 35
#2Paola Nicoletti (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 7
Last. Mia WadeliusH-Index: 47
view all 37 authors...
Background & Aims We performed genetic analyses of a multiethnic cohort of patients with idiosyncratic drug-induced liver injury (DILI) to identify variants associated with susceptibility. Methods We performed a genome-wide association study of 2048 individuals with DILI (cases) and 12,429 individuals without (controls). Our analysis included subjects of European (1806 cases and 10,397 controls), African American (133 cases and 1,314 controls), and Hispanic (109 cases and 718 controls) ancestry....
48 CitationsSource
#1Hideki Yorifuji (Osaka University)H-Index: 1
#2Noriko Arase (Osaka University)H-Index: 20
Last. Hisashi Arase (Osaka University)H-Index: 57
view all 7 authors...
Abstract HLA class I molecules play a central role in the immune system by presenting peptide antigens to cytotoxic T cells. Although most HLA class I molecules are associated with β2-microglobulin, HLA class I heavy chain that is not associated with β2-microglobulin is also expressed on certain cells. We recently found that cellular misfolded proteins are transported to the cell surface by HLA class II molecules via association with their peptide-binding grooves. Furthermore, misfolded self-ant...
1 CitationsSource
Cited By2
#1Takeshi Susukida (University of Toyama)H-Index: 5
#2Saki Kuwahara (Chiba University)
Last. Kousei Ito (Chiba University)H-Index: 29
view all 6 authors...
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...
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...