Objective: Systemic lupus erythematosus (SLE) has substantial unmet medical need and its pathogenesis is incompletely understood. This study characterized baseline gene expression and pharmacodynamic (PD)-induced changes in whole blood gene expression from two phase III, 52-week (W), randomized, placebo-controlled, double-blind studies of 1,760 SLE patients treated with the B cell activating factor (BAFF)-blocking IgG4 monoclonal antibody, tabalumab. Methods: Patient samples were obtained from ILLUMINATE-1 and -2 while control samples were from healthy donors. Blood was collected in TempusTM tubes at baseline, W16 and W52. RNA was analyzed using the Affymetrix Human Transcriptome Array 2.0 and NanoStringTM. Results: At baseline there was elevation of interferon responsive genes (IRG) in patients compared to controls, with 75% positive for this IRG signature. There was, however, substantial heterogeneity of IRG expression and complex relationships among gene networks. The interferon signature was a predictor of future time to flare, independent of anti-double stranded DNA antibody (dsDNA), C3 and C4 levels, and overall disease activity. PD changes in gene expression following tabalumab treatment were extensive, occurring predominantly in B cell-related and immunoglobulin (Ig) genes, and were consistent with other PD-induced changes including dsDNA, C3, and Ig levels. Conclusions: SLE patients demonstrated elevated expression of an IRG signature, detected in 75% of the patients at baseline in ILLUMINATE-1 and -2. There was substantial heterogeneity of gene expression detected among individual patients and in gene networks. The interferon signature was an independent risk factor for future flares. PD changes in gene expression were consistent with the mechanism of BAFF blockade by tabalumab.
Gene Expression and Pharmacodynamic Changes in 1,760 Systemic Lupus Erythematosus Patients From Two Phase III Trials of BAFF Blockade With Tabalumab.
Sex, Specimen part, Race, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene Expression and Pharmacodynamic Changes in 1,760 Systemic Lupus Erythematosus Patients From Two Phase III Trials of BAFF Blockade With Tabalumab.
Sex, Specimen part, Race, Subject, Time
View SamplesObjective: Systemic lupus erythematosus (SLE) has substantial unmet medical need and its pathogenesis is incompletely understood. This study characterized baseline gene expression and pharmacodynamic (PD)-induced changes in whole blood gene expression from two phase III, 52-week (W), randomized, placebo-controlled, double-blind studies of 1,760 SLE patients treated with the B cell activating factor (BAFF)-blocking IgG4 monoclonal antibody, tabalumab. Methods: Patient samples were obtained from ILLUMINATE-1 and -2 while control samples were from healthy donors. Blood was collected in TempusTM tubes at baseline, W16 and W52. RNA was analyzed using the Affymetrix Human Transcriptome Array 2.0 and NanoStringTM. Results: At baseline there was elevation of interferon responsive genes (IRG) in patients compared to controls, with 75% positive for this IRG signature. There was, however, substantial heterogeneity of IRG expression and complex relationships among gene networks. The interferon signature was a predictor of future time to flare, independent of anti-double stranded DNA antibody (dsDNA), C3 and C4 levels, and overall disease activity. PD changes in gene expression following tabalumab treatment were extensive, occurring predominantly in B cell-related and immunoglobulin (Ig) genes, and were consistent with other PD-induced changes including dsDNA, C3, and Ig levels. Conclusions: SLE patients demonstrated elevated expression of an IRG signature, detected in 75% of the patients at baseline in ILLUMINATE-1 and -2. There was substantial heterogeneity of gene expression detected among individual patients and in gene networks. The interferon signature was an independent risk factor for future flares. PD changes in gene expression were consistent with the mechanism of BAFF blockade by tabalumab.
Gene Expression and Pharmacodynamic Changes in 1,760 Systemic Lupus Erythematosus Patients From Two Phase III Trials of BAFF Blockade With Tabalumab.
Sex, Specimen part, Race, Subject, Time
View SamplesObjective: Systemic lupus erythematosus (SLE) has substantial unmet medical need and its pathogenesis is incompletely understood. This study characterized baseline gene expression and pharmacodynamic (PD)-induced changes in whole blood gene expression from two phase III, 52-week (W), randomized, placebo-controlled, double-blind studies of 1,760 SLE patients treated with the B cell activating factor (BAFF)-blocking IgG4 monoclonal antibody, tabalumab. Methods: Patient samples were obtained from ILLUMINATE-1 and -2 while control samples were from healthy donors. Blood was collected in TempusTM tubes at baseline, W16 and W52. RNA was analyzed using the Affymetrix Human Transcriptome Array 2.0 and NanoStringTM. Results: At baseline there was elevation of interferon responsive genes (IRG) in patients compared to controls, with 75% positive for this IRG signature. There was, however, substantial heterogeneity of IRG expression and complex relationships among gene networks. The interferon signature was a predictor of future time to flare, independent of anti-double stranded DNA antibody (dsDNA), C3 and C4 levels, and overall disease activity. PD changes in gene expression following tabalumab treatment were extensive, occurring predominantly in B cell-related and immunoglobulin (Ig) genes, and were consistent with other PD-induced changes including dsDNA, C3, and Ig levels. Conclusions: SLE patients demonstrated elevated expression of an IRG signature, detected in 75% of the patients at baseline in ILLUMINATE-1 and -2. There was substantial heterogeneity of gene expression detected among individual patients and in gene networks. The interferon signature was an independent risk factor for future flares. PD changes in gene expression were consistent with the mechanism of BAFF blockade by tabalumab.
Gene Expression and Pharmacodynamic Changes in 1,760 Systemic Lupus Erythematosus Patients From Two Phase III Trials of BAFF Blockade With Tabalumab.
Sex, Specimen part, Race, Subject, Time
View SamplesWhole exome sequencing identified frequent driver mutations in a series of paediatric glioblastomas
Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma.
Sex, Age, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
E2f8 mediates tumor suppression in postnatal liver development.
Age, Specimen part
View SamplesE2Fs are regulators of the cell cycle and are involved in development. In this study we examine transcriptional changes occurring the liver in E2f1 (1KI) and E2f3b (3bKI) knock in mice. These mice have E2f1 or E2f3b knocked into the E2F3a locus resulting in loss of E2f3a and expression of E2f1 or E2f3b from the E2f3a locus as originally described In Tsai et. al., Nature 2008.
E2f8 mediates tumor suppression in postnatal liver development.
Age, Specimen part
View SamplesE2Fs are regulators of the cell cycle and are involved in development and hepatocellular carcinoma. In this study we examine transcriptional changes occurring the liver in E2f1 (1KI) and E2f3b (3bKI) knock in mice. These mice have E2f1 or E2f3b knocked into the E2F3a locus resulting in loss of E2f3a and expression of E2f1 or E2f3b from the E2f3a locus as originally described In Tsai et. al., Nature 2008.
E2f8 mediates tumor suppression in postnatal liver development.
Age, Specimen part
View SamplesMany neural progenitor cells present in the fetus, but also in adult brain, which play a major role for the reproduction for healingin regeneration of neuronal cells, when differentiated cells are damaged. However, effects of radiation effect on undifferentiated neural progenitor cells remained unclear. The radiation doses of medical exposure, pollution by nuclear power plant accidents, and other exposure of workers; medical workers, airline crews, and astronaut have been focused. In this study, we report the effects of low- to middle- dose doses of radiation on cultured human neural progenitor cells (hNPC) differentiated derived from embryonic stem (ES) cells, which are partially compared with those of human umbilical vein endothelial cell (HUVEC).
Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells.
Specimen part, Cell line
View SamplesBulk RNA sequencing data from neural progenitor cells under conditions of low or high growth factor and Notch pathway activation Overall design: Cells were treated with high (20 ng/ml EGF and FGF) or low (0.5 ng/ml EGF) recombinant growth factors, with or without Notch pathway inhibitor (DAPT, 10 uM) for 12h.
<i>Cis-</i>activation in the Notch signaling pathway.
Specimen part, Subject
View Samples