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GSE45987
Homo sapiens
298 Downloadable Samples
Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A comprehensive analysis of adiponectin QTLs using SNP association, SNP cis-effects on peripheral blood gene expression and gene expression correlation identified novel metabolic syndrome (MetS) genes with potential role in carcinogenesis and systemic inflammation.
Sample Metadata Fields
Sex, Age, Race
View Samples- Homo sapiens
- 320 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
New measures are needed to predict type 1 diabetes disease trajectory. We have developed a sensitive array-based bioassay whereby patient plasma is used to induce transcription in healthy reporter leukocytes. Here we report a refined gene ontology-based inflammatory index (I.I.359) that is based upon expression levels of 359 transcripts identified in cross-sectional studies of new onset Type 1 diabetes patients and controls, where higher scores reflect greater inflammatory bias. We examined the relationship between I.I.359 measured at onset and the post-onset disease course in local patients as well as participants of the TrialNet CTLA4-Ig trial. In untreated patients, I.I.359 at baseline was highly variable and exhibited a significant inverse relationship with stimulated C-peptide AUC at 3, 6, 12, 18 and 24 months post-onset. Further, duration of the post-onset partial remission was negatively related to baseline I.I.359 and positively associated with the peripheral abundance of activated regulatory T cells (CD4+/CD45RA-/FoxP3high).
Publication Title
Innate immune activity as a predictor of persistent insulin secretion and association with responsiveness to CTLA4-Ig treatment in recent-onset type 1 diabetes.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 275 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery, necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding selection of therapy, and monitoring interventions. Previously, we determined that plasma of recent-onset (RO) Type 1 diabetes (T1D) patients induce a proinflammatory transcriptional signature in fresh peripheral blood mononuclear cells (PBMC) relative to that of unrelated healthy controls (HC). Here, using an optimized cryopreserved PBMC-based protocol, we analyzed larger RO T1D, HC, and healthy T1D sibling cohorts. In addition, we examined T1D progression by looking at longitudinal samples.
Publication Title
Molecular signatures differentiate immune states in type 1 diabetic families.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 228 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Blocking the action of the pro-inflammatory cytokine interleukin-1 (IL-1) reduces beta-cell secretory dysfunction and apoptosis in vitro, diabetes incidence in animal models of Type 1 diabetes mellitus (T1D), and glycaemia via improved beta-cell function in patients with T2D. We hypothesised that anakinra, a recombinant human IL-1 receptor antagonist, improves beta-cell function in patients with new-onset T1D. Methods: In an individually randomised, two-group parallel trial involving 14 European tertiary referral centers, 69 patients aged 18-35 with T1D, < 12 weeks of symptoms, and standard mixed meal test (MMT) stimulated C-peptide 200 pM were enrolled between January, 2009 and July, 2011 and assigned by centralised computer-generated blocked randomisation with locked computer-file concealment to treatment with 100 mg anakinra (n=35) subcutaneously once daily or placebo (n=34) for 9 months as add-on to conventional therapy. Participants and care-givers, but not data monitoring unit, were masked to group assignment. The primary end-point was change in the two-hour area-under-the-curve C-peptide response to MMT, and secondary end-points changes in insulin requirements, glycaemia, and inflammatory markers at one, three, six, and nine months. Findings: The study was prematurely terminated due to slow accrual and is closed to follow-up. No interim analysis was performed. Ten patients withdrew in the anakinra and eight in the placebo arm, leaving 25 and 26 patients to be analysed, respectively. There was no statistical difference in adverse event category reporting between arms. Interpretation: Anakinra-treatment in T1D was safe, but the trial failed to meet primary and secondary outcome measures.
Publication Title
Interleukin-1 antagonism moderates the inflammatory state associated with Type 1 diabetes during clinical trials conducted at disease onset.
Sample Metadata Fields
Subject, Time
View Samples- Homo sapiens
- 202 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptional signatures as a disease-specific and predictive inflammatory biomarker for type 1 diabetes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 187 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Blocking the action of the pro-inflammatory cytokine interleukin-1 (IL-1) reduces beta-cell secretory dysfunction and apoptosis in vitro, diabetes incidence in animal models of Type 1 diabetes mellitus (T1D), and glycaemia via improved beta-cell function in patients with T2D. We hypothesised that canakinumab, a monoclonal antibody to IL-1B, improves beta-cell function in patients with new-onset T1D. Methods: In an individually randomised, two-group parallel trial involving 12 sites in US, 69 patients aged 6-45 with T1D, < 12 weeks of symptoms, and assigned by centralised computer-generated blocked randomisation with locked computer-file concealment to treatment with 2 mg/kg (maximum 300 mg) canakinumab (n=45) or placebo (n=22) monthly for 12 months as add-on to conventional therapy. Participants and care-givers, but not data monitoring unit, were masked to group assignment. The primary end-point was change in the two-hour area-under-the-curve C-peptide response to MMT 12 months.
Publication Title
Interleukin-1 antagonism moderates the inflammatory state associated with Type 1 diabetes during clinical trials conducted at disease onset.
Sample Metadata Fields
Subject, Time
View Samples- Homo sapiens
- 134 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery, necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding selection of therapy, and monitoring interventions. Previously, we determined that plasma of recent-onset (RO) Type 1 diabetes (T1D) patients induce a proinflammatory transcriptional signature in fresh peripheral blood mononuclear cells (PBMC) relative to that of unrelated healthy controls (HC). Here, using an optimized cryopreserved PBMC-based protocol, we compared the signature found between unrelated healthy controls and non-diabetic cystic fibrosis patients possessing Pseudomonas aeruginosa pulmonary tract infection.
Publication Title
Identification of molecular signatures of cystic fibrosis disease status with plasma-based functional genomics.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 114 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery, necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding selection of therapy, and monitoring interventions. Previously, we determined that plasma of recent-onset (RO) Type 1 diabetes (T1D) patients induce a proinflammatory transcriptional signature in fresh peripheral blood mononuclear cells (PBMC) relative to that of unrelated healthy controls (HC). Here, using an optimized cryopreserved PBMC-based protocol, we analyzed larger RO T1D and HC cohorts. In addition, we examined T1D progression by looking at longitudinal, pre-onset and longstanding T1D samples.
Publication Title
Transcriptional signatures as a disease-specific and predictive inflammatory biomarker for type 1 diabetes.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 58 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of a novel gene for diabetic traits in rats, mice, and humans.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Rattus norvegicus
- 77 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Age, Specimen part
View Samples