Related Experiment Video
Updated: Jun 23, 2026
11:49
Trans-vivo Delayed Type Hypersensitivity Assay for Antigen Specific Regulation
Published on: May 2, 2013
16.1K
Pharmacodynamic monitoring by residual gene expression of the nuclear factor of activated T cell-regulated genes in
Meritxell Boada-Pérez1,2, Victoria Ruiz de Miguel2, Marta Erro3
1Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Frontiers in Immunology
|May 27, 2024
Summary
Tacrolimus peak levels, not trough levels, correlate with immune suppression in lung transplant recipients. Monitoring nuclear factor of activated T cell-regulated genes (NFAT-RGE) may help personalize immunosuppression therapy.
Area of Science:
- Immunology
- Pharmacology
- Transplantation Medicine
Background:
- Tacrolimus trough blood levels (C0) are standard for dosing but poorly correlate with clinical outcomes in lung transplant recipients (LTR).
- Nuclear factor of activated T cell (NFAT)-regulated gene expression (NFAT-RGE) is a potential pharmacodynamic biomarker for immunosuppression, but its utility in LTR is understudied.
Purpose of the Study:
- To correlate tacrolimus blood levels (C0 and C1.5) with NFAT-RGE in LTR.
- To assess the potential of NFAT-RGE as a biomarker for immunosuppression monitoring in LTR.
Main Methods:
- NFAT-RGE and tacrolimus C0 and peak (C1.5) levels were measured in 42 LTR at 3, 6, and 12 months post-transplantation.
- Correlation analysis was performed between tacrolimus levels and NFAT-RGE.
Main Results:
- Tacrolimus C0 did not correlate with NFAT-RGE, while C1.5 showed a correlation.
- Over 20% of measurements indicated high immunosuppression (NFAT-RGE < 30%).
- 19% of measurements within the therapeutic tacrolimus range showed NFAT-RGE < 30%.
Conclusions:
- Tacrolimus peak levels (C1.5) and NFAT-RGE are better indicators of immunosuppression than trough levels (C0) in LTR.
- A subset of LTR within the therapeutic tacrolimus range may be over-immunosuppressed, increasing risks for infection and cancer.
- Monitoring NFAT-RGE alongside tacrolimus peak levels may allow for personalized immunosuppression management in LTR.
Related Concept Videos
01:16Therapeutic Drug Monitoring: Overview and Classification
Therapeutic Drug Monitoring (TDM) is a clinical practice that measures specific drug levels in a patient's blood at designated intervals to ensure the drug concentration stays within a therapeutic range. This monitoring is crucial for optimizing individual dosage regimens, enhancing therapeutic efficacy, and minimizing drug-related toxicity. TDM is vital for drugs with narrow therapeutic windows, significant variability in pharmacokinetics, and a clear correlation between plasma levels and...
01:29Therapeutic Drug Monitoring: Affecting Factors
Therapeutic Drug Monitoring (TDM) is the clinical practice of measuring specific drug levels in a patient's blood or body tissues to manage and optimize therapy. TDM is crucial for drugs with narrow therapeutic windows, like warfarin and phenytoin, where incorrect doses can lead to treatment failure or severe side effects. This monitoring ensures the dosage administered is within a safe and effective range. The factors affecting therapeutic drug monitoring include:Patient-Specific Factors:a.
01:26Therapeutic Drug Monitoring: Drug Analysis Methods
Therapeutic Drug Monitoring (TDM) is a clinical practice that measures specific drug levels in a patient's blood or body tissues to tailor drug therapy effectively. This monitoring is critical for managing drugs with narrow therapeutic indices like digoxin and phenytoin, ensuring they are both safe and effective. For instance, monitoring theophylline levels in asthma patients involves precision and sensitivity to adjust doses according to individual responses to therapy, ensuring efficacy and...
01:27Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...