Please use this identifier to cite or link to this item: doi:10.22028/D291-31855
Title: A Polyclonal Immune Function Assay Allows Dose-Dependent Characterization of Immunosuppressive Drug Effects but Has Limited Clinical Utility for Predicting Infection on an Individual Basis
Author(s): Marx, Stefanie
Adam, Claudia
Mihm, Janine
Weyrich, Michael
Sester, Urban
Sester, Martina
Language: English
Title: Frontiers in Immunology
Volume: 11
Publisher/Platform: Frontiers
Year of Publication: 2020
Free key words: immunomonitoring
transplantation
immunosuppression
infection
pharmacodynamics
pharmacokinetics
T-cell
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: Dosage of immunosuppressive drugs after transplantation critically determines rejection and infection episodes. In this study, a global immune function assay was characterized among controls, dialysis-patients, and transplant-recipients to evaluate its utility for pharmacodynamic monitoring of immunosuppressive drugs and for predicting infections. Whole-blood samples were stimulated with anti-CD3/toll-like-receptor (TLR7/8)-agonist in the presence or absence of drugs and IFN-γ secretion was measured by ELISA. Additional stimulation-induced cytokines were characterized among T-, B-, and NK-cells using flow-cytometry. Cytokine-secretion was dominated by IFN-γ, and mainly observed in CD4, CD8, and NK-cells. Intra-assay variability was low (CV = 10.4 ± 6.2%), whereas variability over time was high, even in the absence of clinical events (CV = 65.0 ± 35.7%). Cyclosporine A, tacrolimus and steroids dose-dependently inhibited IFN-γ secretion, and reactivity was further reduced when calcineurin inhibitors were combined with steroids. Moreover, IFN-γ levels significantly differed between controls, dialysis-patients, and transplant-recipients, with lowest IFN-γ levels early after transplantation (p < 0.001). However, a single test had limited ability to predict infectious episodes. In conclusion, the assay may have potential for basic pharmacodynamic characterization of immunosuppressive drugs and their combinations, and for assessing loss of global immunocompetence after transplantation, but its application to guide drug-dosing and to predict infectious on an individual basis is limited.
DOI of the first publication: 10.3389/fimmu.2020.00916
Link to this record: urn:nbn:de:bsz:291--ds-318550
hdl:20.500.11880/29494
http://dx.doi.org/10.22028/D291-31855
ISSN: 1664-3224
Date of registration: 6-Aug-2020
Description of the related object: Supplementary Material
Related object: https://www.frontiersin.org/articles/10.3389/fimmu.2020.00916/full#supplementary-material
Faculty: M - Medizinische Fakultät
Department: M - Infektionsmedizin
Professorship: M - Prof. Dr. Martina Sester
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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