دورية أكاديمية
أعرض في EDS

Pharmacodynamic Effect of mTOR Inhibition-based Immunosuppressive Therapy on T- and B-cell Subsets After Renal Transplantation.

التفاصيل البيبلوغرافية
العنوان: Pharmacodynamic Effect of mTOR Inhibition-based Immunosuppressive Therapy on T- and B-cell Subsets After Renal Transplantation.
المؤلفون: Wei X; Pediatric Gastroenterology and Hepatology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.; Department for Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Weber S; Pediatric Gastroenterology and Hepatology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany., Yin D; Pediatric Gastroenterology and Hepatology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany., Allabauer I; Pediatric Gastroenterology and Hepatology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany., Jobst-Schwan T; Department of Nephrology and Hypertension, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany., Wiesener M; Department of Nephrology and Hypertension, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany., Schiffer M; Department of Nephrology and Hypertension, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany., Dudziak D; Institute of Immunology, Friedrich-Schiller University Jena, Jena, Germany.; Laboratory of Dendritic Cell Biology, Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany., Lehmann CHK; Pediatric Gastroenterology and Hepatology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.; Laboratory of Dendritic Cell Biology, Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.; FAU Profile Center Immunomedicine, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany.; Deutsches Zentrum Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany., Woelfle J; Pediatric Gastroenterology and Hepatology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.; Deutsches Zentrum Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany., Hoerning A; Pediatric Gastroenterology and Hepatology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.; FAU Profile Center Immunomedicine, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany.; Deutsches Zentrum Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
المصدر: Transplantation direct [Transplant Direct] 2024 Jun 20; Vol. 10 (7), pp. e1666. Date of Electronic Publication: 2024 Jun 20 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Wolters Kluwer Country of Publication: United States NLM ID: 101651609 Publication Model: eCollection Cited Medium: Print ISSN: 2373-8731 (Print) Linking ISSN: 23738731 NLM ISO Abbreviation: Transplant Direct Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Philadelphia, Pa.] : Wolters Kluwer, [2015]-
مستخلص: Background: The mammalian target of rapamycin inhibitor (mTORi) therapy after kidney transplantation is solely monitored pharmacokinetically, not necessarily reflecting PI3K-Akt-mTOR pathway blockade efficacy leading to potential under-or overimmunosuppression.
Methods: In this cross-sectional study, phosphoflow cytometry was used to determine the efficacy of mTOR inhibition in peripheral T- and B-lymphocyte subsets by assessing p70S6 kinase (p70S6K) phosphorylation in renal transplant recipients upon treatment with a combination of either mTORi and calcineurin inhibitors (n = 18), or mTORi with mycophenolic acid (n = 9). Nine dialysis patients with end-stage renal disease and 17 healthy age-matched volunteers served as controls.
Results: mTORi treatment reduced p70S6K phosphorylation in CD4 + , CD8 + T, and CD19 + B cells compared with healthy controls (HCs). Subpopulation analysis of CD4 + T cells and CD19 + B cells revealed a significant reduction of p70S6K phosphorylation in CD4 + CD45RA - CD25 - Th cells ( P  < 0.05), CD24 hi CD38 hi transitional B cells ( P  < 0.001), CD24 + CD38 - memory B cells ( P  < 0.001), and CD24 int CD38 int -naive B cells ( P  < 0.05) upon mTORi treatment, whereas CD4 + CD45RA - CD25 ++ CD127 - regulatory T cells and CD24 - CD38 hi plasmablasts were not affected. Compared with mTORi + mycophenolic acid therapy, mTORi + calcineurin inhibitor treatment exhibited an even stronger inhibition of p70S6K phosphorylation in CD4 + CD45RA - CD25 - Th cells and CD8 + T cells. However, trough levels of mTORi did not correlate with p70S6K phosphorylation.
Conclusions: mTORi selectively inhibited p70S6K phosphorylation in select lymphocyte subtypes. Assessing p70S6K phosphorylation by phosphoflow cytometry may serve as an approach to understand cell subset specific effects of mTORi providing detailed pharmacodynamic information for individualizing immunosuppression.
Competing Interests: The authors declare no conflicts of interest.
(Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)
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تواريخ الأحداث: Date Created: 20240624 Latest Revision: 20240625
رمز التحديث: 20240625
مُعرف محوري في PubMed: PMC11191901
DOI: 10.1097/TXD.0000000000001666
PMID: 38911271
قاعدة البيانات: MEDLINE
الوصف
تدمد:2373-8731
DOI:10.1097/TXD.0000000000001666