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 SamplesThe goal of this study was to characterize gene expression profiles in RNP autoantibody+ SLE versus healthy blood donors with a focus on select cytokines that may be important in B cell activation and differentiation, including BAFF, IL-21, and IL-33. We utilized Affymetrix microarrays to characterize the global program of gene expression in the SLE patients, and to identify differentially expressed genes in patients compared to healthy controls. We examined a cohort of 79 consecutive patients classified as anti-ribonuclear protein (anti-RNP)+ systemic lupus erythematosus (SLE). All patients provided RNA samples obtained after providing informed consent. There were 73 female and 6 male subjects. Disease duration ranged from 0 to 453 months with a median of 37.5 months. SLE Disease Activity Index (SLEDAI) ranged from 0 to 31 with a median of 6.
No associated publication
Specimen part, Disease
View SamplesGlobal microarray (HG U133 Plus 2.0) was used to investigate the effects of resistance exercise and resistance training on the skeletal muscle transcriptome profile of 28 young and old adults. Vastus lateralis muscle biopsies were obtained pre and 4hrs post resistance exercise in the beginning (untrained state) and at the end (trained state) of a 12 wk progressive resistance training program.
Transcriptome signature of resistance exercise adaptations: mixed muscle and fiber type specific profiles in young and old adults.
Sex, Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Stromal-Based Signatures for the Classification of Gastric Cancer.
Sex, Specimen part
View SamplesIncreasing success is being achieved in the treatment of malignancies with stromal-targeted therapies, predominantly in anti-angiogenesis and immunotherapy, predominantly checkpoint inhibitors. Despite 15 years of clinical trials with anti-VEGF pathway inhibitors for cancer, we still find ourselves lacking reliable predictive biomarkers to select patients for anti-angiogenesis therapy. For the more recent immunotherapy agents, there are many approaches for patient selection under investigation. Notably, the predictive power of an Ad-VEGF-A164 mouse model to drive a stromal response with similarities to a wound healing response shows relevance for human cancer and was used to generate stromal signatures. We have developed gene signatures for 3 stromal states and leveraged the data from multiple large cohort bioinformatics studies of gastric cancer (TCGA, ACRG) to further understand how these relate to the dominant patient phenotypes identified by previous bioinformatics efforts. We have also designed multiplexed IHC assays that robustly represent the vascular and immune diversity in gastric cancer. Finally, we have used this methodology to arrive at a hypothesis of how angiogenesis and immunotherapy may fit into the experimental approaches for gastric cancer treatments.
Stromal-Based Signatures for the Classification of Gastric Cancer.
Sex, Specimen part
View SamplesGlobal microarray (HG U133 Plus 2.0) was used for the first time to investigate the effects of resistance exercise on the transcriptome in slow-twitch myosin heavy chain (MHC) I and fast-twitch MHC IIa muscle fibers of young and old women. Vastus lateralis muscle biopsies were obtained pre and 4hrs post resistance exercise in the beginning (untrained state) and at the end (trained state) of a 12 wk progressive resistance training program.
Transcriptome signature of resistance exercise adaptations: mixed muscle and fiber type specific profiles in young and old adults.
Sex, Specimen part, Subject, Time
View SamplesGlobal microarray (HG U133 Plus 2.0) was used to investigate the basal level skeletal muscle transcriptome profile of young and old adults. One vastus lateralis muscle biopsy was obtained in the basal state from 36 different subjects.
Transcriptome signature of resistance exercise adaptations: mixed muscle and fiber type specific profiles in young and old adults.
Sex, Specimen part
View Samples