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- W77893092 abstract "Abstract Contemporary immunosuppressive protocols rely on drug dosing guidelines gleaned from large clinical trials, but the effect of this therapy in a transplant recipient remains difficult to predict. To assess global immunosuppression in individual patients, we measured the degree to which NFkB translocation in peripheral T cells was impaired by conventional immunosuppressive therapy. NFkB is a ubiquitously expressed transcription factor normally sequestered in the cytoplasm. Upon activation, NFkB inhibitors are degraded, releasing NFkB to translocate to the nucleus. The abundance of NFkB in the nucleus vs. the cytosol reflects the activation state of a particular cell type. Peripheral blood cells were isolated from 17 subjects, stimulated in culture for 24 hrs with PMA and ionomycin and stained for T cell surface markers and the major intracellular isoform of NFkB, RelA or p65. Using Amnis Imagestream technology, we compared nuclear NFkB in resting and activated CD3, CD4 and CD8 T cell subsets. Compared to normal controls (n=8), transplant recipients on tacrolimus, MPA and prednisone showed reduced translocation of NFkB to the nucleus. Patients with stable allograft function (n=5) had a 36-75% reduction in nuclear NFkB translocation in all 3 T cell subsets. In contrast, patients with acute rejection (n=2) had an increase in ability to translocate NFkB in CD3 and CD8 cells and only a 9% suppression in CD4 cells. Patients with viral infections (n=2) had severely compromised NFkB translocation with 100% suppression in CD3 and CD4 subsets and 92% suppression in CD8 T cells. NFkB inhibition strongly correlates with overall immunosuppression and clinical outcomes. The novel Amnis Imagestream assay may be a useful guide to individualizing immune therapy or directing minimization strategies. (unfunded)" @default.
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- W77893092 date "2009-04-01" @default.
- W77893092 modified "2023-09-27" @default.
- W77893092 title "A novel method to assess the level of immunosupression in transplant patients using Amnis ImageStream technology (141.24)" @default.
- W77893092 doi "https://doi.org/10.4049/jimmunol.182.supp.141.24" @default.
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