Nuclear factor of activated T cells-regulated gene expression as predictive biomarker of personal response to calcineurin inhibitors

• Verfasst von: Sommerer, Claudia [VerfasserIn]
• Verfasst von: Giese, Thomas [VerfasserIn]
• Titel: Nuclear factor of activated T cells-regulated gene expression as predictive biomarker of personal response to calcineurin inhibitors
• Verf.angabe: Sommerer, Claudia MD, MSc, Giese, Thomas MD
• E-Jahr: 2016
• Jahr: April 2016
• Umfang: 6 S.
• Fussnoten: Gesehen am 12.05.2020
• Titel Quelle: Enthalten in: Therapeutic drug monitoring
• Ort Quelle: Philadelphia, Pa. : Lippincott Williams & Wilkins, 1979
• Jahr Quelle: 2016
• Band/Heft Quelle: 38(2016), Seite S50-S56
• ISSN Quelle: 1536-3694
• DOI: doi:10.1097/FTD.0000000000000234
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1697760252

Abstract

Calcineurin inhibitors (CNIs) represent the most widely used immunosuppressive agents in kidney transplantation. Both CNIs show a narrow therapeutic window; thus, monitoring is necessary to balance efficacy and toxicity. Several approaches have been undertaken to measure the biological effects of CNI-based immunosuppression. - Methods: - A quantitative analysis of gene expression was established to calculate the functional effects of calcineurin inhibition, the assessment of nuclear factor of activated T cells (NFAT)-regulated gene expression. This assay is based on the quantitative analysis of interleukin-2, interferon-γ, and granulocyte macrophage colony-stimulating factor gene expression in whole blood samples collected at the time cyclosporine A/tacrolimus troughs (C0) and 2 hours after oral uptake (C2). - Results: - In this comprehensive review, analytical aspects of the assay and also clinical benefits and limitations are presented and discussed. Several observational studies underline the beneficial effect of NFAT-regulated gene expression as biomarker of personal response on CNI therapy, especially in infectious complications, malignancies, and acute rejection episodes. Data are more comprehensive in cyclosporine A compared with tacrolimus therapy. However, results on prospective interventional studies are sparse. A randomized controlled study evaluating the opportunity for NFAT-guided immunosuppression is ongoing. - Conclusions: - NFAT-regulated gene expression is a promising biomarker in CNI therapy concerning infectious complications, malignancies, and acute rejection. Prospective interventional studies and randomized controlled studies are ongoing to confirm the encouraging results.