Genetic aspects of immune-mediated adverse drug effects

Bugelski, Peter J.

doi:10.1038/nrd1605

Cited by 23 publications

(12 citation statements)

References 109 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For instance, MHC proteins, T-cell receptors and some cellular drug metabolizing enzymes (i.e. cytochrome P450 and Phase II metabolizing enzymes) can contribute to the hapten formation and ensuing immunological responses [34]. Although, when the hapten is completely developed and presented at the surface of a nascent T-cell and B-cell clone, they need to proliferate and fully exert their cellular actions.…”

Section: Discussionmentioning

confidence: 99%

Association of HLA-B*5801 allele and allopurinol-induced stevens johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis

et al. 2011

View full text Add to dashboard Cite

BackgroundDespite some studies suggesting a possible association between human leukocyte antigen, HLA-B*5801 and allopurinol induced Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), the evidence of association and its magnitude remain inconclusive. This study aims to systematically review and meta-analyze the association between HLA-B*5801 allele and allopurinol-induced SJS/TEN.MethodsA comprehensive search was performed in databases including MEDLINE, Pre-MEDLINE, Cochrane Library, EMBASE, International Pharmaceutical Abstracts (IPA), CINAHL, PsychInfo, the WHO International, Clinical Trial Registry, and ClinicalTrial.gov from their inceptions to June 2011. Only studies investigating association between HLA-B*5801 with allopurinol-induced SJS/TEN were included. All studies were extracted by two independent authors. The primary analysis was the carrier frequency of HLA-B*5801 comparison between allopurinol-induced SJS/TEN cases and each comparative group. The pooled odds ratios were calculated using a random effect model.ResultsA total of 4 studies with 55 SJS/TEN cases and 678 matched-controls (allopurinol-tolerant control) was identified, while 5 studies with 69 SJS/TEN cases and 3378 population-controls (general population) were found. SJS/TEN cases were found to be significantly associated with HLA-B*5801 allele in both groups of studies with matched-control (OR 96.60, 95%CI 24.49-381.00, p < 0.001) and population-control (OR 79.28, 95%CI 41.51-151.35, p < 0.001). Subgroup analysis for Asian and Non-Asian population yielded similar findings.ConclusionWe found a strong and significant association between HLA-B*5801 and allopurinol-induced SJS/TEN. Therefore, HLA-B*5801 allele screening may be considered in patients who will be treated with allopurinol.

show abstract

Section: Discussionmentioning

confidence: 99%

Association of HLA-B*5801 allele and allopurinol-induced stevens johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Some drugs such as tienilic acid, amodiaquine and halothane induce hepatic hypersensitivity reactions (Bugelski, 2005). The pathogenesis of drug-induced liver injury usually involves the participation of the parent drug or metabolites that either directly affect the cell biochemistry or elicit an immune response.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-17 is involved in α-naphthylisothiocyanate-induced liver injury in mice

et al. 2010

View full text Add to dashboard Cite

“…The pathogenesis of drug‐induced liver injury usually involves the participation of the parent drug or metabolites that either directly affect cell functions or elicit an immune response. Some drugs, such as tienilic acid, amodiaquine and halothane, are suggested to induce immune‐related DILI (Bugelski, ). In most cases, the mechanisms underlying DILI are unknown because predictive in vitro screening methods and animal models are lacking.…”

Section: Introductionmentioning

confidence: 99%

Th2 cytokine‐mediated methimazole‐induced acute liver injury in mice

Kobayashi

Higuchi

Ide³

et al. 2012

J of Applied Toxicology

View full text Add to dashboard Cite

Drug-induced liver injury (DILI) is a major safety concern in drug development and clinical practice. The pathogenesis of DILI usually involves the participation of the parent drug or metabolites that either affect cellular function or elicit an immune response. However, the mechanisms leading to DILI are unknown in most cases. Methimazole (MTZ) is used as an antithyroid drug and is well known to have induced liver injuries such as cholestatic hepatitis in a small number of human cases. Immune-mediated reactions were also suggested to play a role in MTZ-induced acute liver injury, but the mechanism underlying this process has not been elucidated. To address this issue, we measured plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, hepatic glutathione levels, hepatic expression of CD4⁺ Th cell-related transcriptional factors, cytokines and chemokines, plasma interleukin (IL)-4 levels and histopathological changes in the liver following MTZ (450 mg kg⁻¹ , p.o.) administration in mice. The hepatic expression of mRNA for Th2 cell-related factors, such as GATA-binding protein, macrophage inflammatory protein-2 (MIP-2) and plasma IL-4 levels, as well as plasma AST and ALT levels, was significantly increased in mice treated with MTZ. These changes were markedly enhanced by pre-treatment with L-buthionine sulfoximine (3 mmol kg⁻¹, i.p.) and MTZ (15 mg kg⁻¹, p.o.). Neutralization of IL-4 using a monoclonal anti-mouse IL-4 antibody (100 µg/mouse, single i.p.) suppressed the hepatotoxic effect of MTZ. In conclusion, this report is the first to demonstrate that Th2 cytokine-mediated immune responses are involved in MTZ-induced acute liver injury in mice.

show abstract

Genetic aspects of immune-mediated adverse drug effects

Cited by 23 publications

References 109 publications

Association of HLA-B*5801 allele and allopurinol-induced stevens johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis

Association of HLA-B*5801 allele and allopurinol-induced stevens johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis

Interleukin-17 is involved in α-naphthylisothiocyanate-induced liver injury in mice

Th2 cytokine‐mediated methimazole‐induced acute liver injury in mice

Contact Info

Product

Resources

About