Pharmacodynamic Effect of mTOR Inhibition-based Immunosuppressive Therapy on T- and B-cell Subsets After Renal Transplantation
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. In this cross-sectional study, phosphoflow cytomet...
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Veröffentlicht in: | Transplantation direct 2024-07, Vol.10 (7), p.e1666 |
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Sprache: | eng |
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Zusammenfassung: | 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.
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.
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 (
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ISSN: | 2373-8731 2373-8731 |
DOI: | 10.1097/TXD.0000000000001666 |