Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen
Autor: | Stella O. Sieber, Kevin Gerrish, Rick D. Fannin, Pierre R. Bushel, Richard S. Paules, Paul B. Watkins |
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Rok vydání: | 2016 |
Předmět: |
Genetic Markers
0301 basic medicine Time Factors Administration Oral Biology Placebo Drug Administration Schedule Article Transcriptome 03 medical and health sciences Th2 Cells 0302 clinical medicine Immune system Double-Blind Method Predictive Value of Tests Gene expression medicine Humans Pharmacology (medical) RNA Messenger Acetaminophen Pharmacology Liver injury Principal Component Analysis Innate immune system Gene Expression Profiling Alanine Transaminase Analgesics Non-Narcotic medicine.disease Immunity Innate Up-Regulation 030104 developmental biology Immunology Biomarker (medicine) Chemical and Drug Induced Liver Injury Drug Monitoring 030215 immunology medicine.drug |
Zdroj: | Clinical Pharmacology & Therapeutics. 99:432-441 |
ISSN: | 0009-9236 |
Popis: | The diagnosis of drug-induced liver injury is hindered by the limited utility of clinical chemistries. We have shown that hepatotoxicants can produce peripheral blood transcriptome "signatures" (PBTS) in rodents and humans. In this study, 42 adults were treated with acetaminophen (APAP; 1 g every 6 hours) for seven days, followed by three days of placebo. Eleven subjects received only placebo. After five days, 12 subjects (30%) had increases in serum alanine aminotransferase (ALT) levels ("responders"). PBTS of 707 and 760 genes, respectively, could distinguish responders and nonresponders from placebos. Functional analysis of the responder PBTS revealed increased expression of genes involved in TH2-mediated and innate immune responses, whereas the nonresponders demonstrated increased gene expression consistent with a tolerogenic immune response. Taken together, these observations suggest that the clinical subjects with transient increases in serum ALT failed to maintain or intensify a hepatic tolerogenic immune response. |
Databáze: | OpenAIRE |
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