Plasma Nucleotide/adenosine concentrations (Human AxP Batch 4)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
TISSUE(S): Blood
PROVIDER: ST000283 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| mwtab | Other |
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2019-05-28 | PXD010519 | Pride
Project description:Tuberculosis (TB) remains one of the leading causes of mortality worldwide, and a lack of understanding of basic disease pathogenesis is hampering development of new vaccines and treatments. Multiple studies have previously established a role for type I interferon (IFN) in TB disease. Type I IFNs are critical immune mediators for host responses to viral infection, yet their specific influence in bacterial infection remains unclear. As IFN-stimulated genes (ISGs) can have both stimulatory and inhibitory effects on immune function, clarifying the role of type I interferon in TB remains an important question. The quantification of interferon proteins in the circulation of patients has been restricted until the recent development of digital ELISA. To test the hypothesis that patients with active TB disease have elevated circulating type I IFN we quantified plasma IFNα and β proteins with Simoa digital ELISA in patients with active disease and asymptomatic M. tuberculosis infection. Strikingly no differences were observed between these two groups, while plasma from acute influenza infection revealed significantly higher plasma levels of both IFNα and IFNβ proteins. These results suggest a discordance between ISG mRNA expression by blood leukocytes and circulating type I IFN in TB.
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Project description:Single nucleotide polymorphisms (SNPs) in the genes that encode the cytochrome P450 (CYP) drug metabolizing enzymes and drug transporters have been reported to influence antiretroviral drug pharmacokinetics. Although primarily metabolized by CYP2B6 and -3A, efavirenz (EFV) and lopinavir/ritonavir (LPV/r) are substrates of P-glycoprotein and the solute carrier organic (SLCO) anion transporter, respectively. We investigated the association between SNPs and efavirenz (EFV) or lopinavir/ritonavir (LPV/r) concentrations in Chinese children infected with the human immunodeficiency virus (HIV). Genotyping was performed on CYP2B6 516G→T, -1459C→T, and -983T→C, ABCB1 3435C→T, and SLCO1B1 521T→C in 229 HIV-infected Chinese pediatric patients (age range 4.0 to 17.5 yrs). Plasma concentrations of EFV and LPV/r were measured using validated high-performance liquid chromatography coupled with the mass spectrum method among 39 and 69 children who received EFV- and LPV/r-containing regimens, respectively. The frequencies of CYP2B6 516G→T in the study participants were 71%, 25%, and 4% for the G/G, G/T, and T/T genotypes, respectively. Among the children under therapeutic drug monitoring, 21% and 39% experienced EFV and LPV concentrations, respectively, above the upper threshold of the therapeutic window. CYP2B6 516G→T was significantly associated with EFV concentrations (p<0.001). Older children (older than 10 yrs) were more likely to have significantly higher EFV concentrations than the younger ones (p=0.0314). CYP2B6 genotyping and EFV concentration monitoring may help optimize antiretroviral therapy in pediatric patients who initiate an EFV-based regimen.
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