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Homo sapiens
232 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Systemic onset Juvenile Idiopathic Arthritis (SoJIA) represents up to 20% of Juvenile Idiopathic Arthritis (JIA). We have previously reported that this disease is Interleukin 1 (IL1)-mediated, and that IL-1 blockade results in clinical remission in the majority of patients. The diagnosis of SoJIA, however, still relies on clinical findings as no specific diagnostic tests are available, which leads to delays in the initiation of specific therapy. To identify specific diagnostic markers, we analyzed gene expression profiles in 19 pediatric patients with SoJIA during the systemic phase of the disease (fever and/or arthritis), 25 SoJIA patients with no systemic symptoms (arthritis only or no symptoms), 39 healthy controls, 94 pediatric patients with acute viral and bacterial infections (available under GSE6269), 38 pediatric patients with Systemic Lupus Erythematosus (SLE), and 6 patients with a second IL-1 mediated disease known as PAPA syndrome. Statistical group comparison and class prediction identified genes differentially expressed in SoJIA patients compared to healthy children. These genes, however, were also changed in patients with acute infections and SLE. By performing an analysis of significance across all diagnostic groups, we generated a list of 88 SoJIA-specific genes (p<0.01 in SoJIA and >0.5 in all other groups). A subset of 12/88 genes permitted us to accurately classify an independent test set of SoJIA patients with systemic disease. We were also able to identify a group of transcripts that changed significantly in patients undergoing IL-1 blockade. Thus, analysis of transcriptional signatures from SoJIA blood leukocytes can help distinguishing this disease from other febrile illnesses and assessing response to therapy. Availability of accurate diagnostic markers for SoJIA patients may allow prompt initiation of effective therapy and prevention of long-term disabilities.
Publication Title
Blood leukocyte microarrays to diagnose systemic onset juvenile idiopathic arthritis and follow the response to IL-1 blockade.
Sample Metadata Fields
Sex, Age, Treatment, Race
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GSE46923- Homo sapiens
- 139 Downloadable Samples
Affymetrix Human Genome U133B Array (hgu133b), Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment, Subject, Time
View Samples- Homo sapiens
- 45 Downloadable Samples
- Affymetrix Human Genome U133B Array (hgu133b), Affymetrix Human Genome U133A Array (hgu133a)
Description
We screened SLE monocytes from 19 SLE patients and selected 4 that induced CD4+ T cell proliferation in vitro and 4 that did not. CFSE labeled CD4-T cells (105) were incubated with SLE monocytes (2 x 104). Cells were harvested at 6 hours for RNA extraction.
Publication Title
IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment, Subject, Time
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Human Genome U133B Array (hgu133b)
Description
To explore the full extent of IFN-regulated transcriptional changes, we exposed monocytes from two healthy donors to recombinant type I IFN (IFN-2b) in vitro. RNA was extracted at different incubation times (1, 6, 24, 48 and 72 hrs) and the expression data was normalized to that of monocytes cultured with medium.
Publication Title
IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment, Time
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133B Array (hgu133b), Affymetrix Human Genome U133A Array (hgu133a)
Description
To directly compare the SLE monocyte transcriptional program with that of blood mDC precursors, we purified lineage HLA-DRhighCD11chigh mDCs and CD14+ monocytes from the blood of five healthy donors. Their gene expression profiles were then compared to those of blood SLE monocytes. An unsupervised clustering analysis of transcripts present in >20% of the samples classified healthy monocytes, SLE monocytes and healthy mDCs into three well defined groups. A supervised analysis was then performed to find genes: 1) differentially expressed in healthy mDCs compared to monocytes; 2) shared by healthy blood mDCs and SLE blood monocytes.
Publication Title
IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133B Array (hgu133b), Affymetrix Human Genome U133A Array (hgu133a)
Description
To better characterize the molecules that could potentially confer antigen presenting capacity to SLE monocytes, we assessed their gene expression profile.
Publication Title
IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133B Array (hgu133b), Affymetrix Human Genome U133A Array (hgu133a)
Description
Monocytes from 3 healthy donors were cultured for 6 hours in the presence of 20% serum from three newly diagnosed, untreated SLE patients. Microarray analysis was then performed upon normalizing the gene expression levels of samples incubated with SLE sera to those incubated with autologous serum.
Publication Title
IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
To explore the full extent of IFN-regulated transcriptional changes, we exposed monocytes from two healthy donors to recombinant type I IFN (IFN-2b) in vitro. RNA was extracted at 6 hrs and the expression data was normalized to that of monocytes cultured with medium.
Publication Title
IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Homo sapiens
- 29 Downloadable Samples
Illumina HiSeq 2500
Description
A better understanding of the molecular and cellular factors involved in human plasma cell differentiation will accelerate therapeutic target identification in autoantibody-mediated diseases such as Systemic Lupus Erythematosus (SLE). Here, we describe a novel CXCR3+ PD1hi CD4+ T cell 'helper' population expanded in blood and inflamed kidneys of SLE patients. Upon activation, these cells express IFNg and IL10 and display high levels of mitochondrial ROS (mtROS) as the result of reverse electron transfer (RET) fueled by succinate. Furthermore, T cell-derived succinate synergizes with IL10 to provide B cell help. Cells with similar phenotype and function are generated in vitro upon priming naive CD4+ T cells with oxidized mitochondrial DNA (Ox mtDNA)- activated plasmacytoid dendritic cells (pDCs) in a PD1-dependent manner. Our results provide a novel mechanism for the initiation and/or perpetuation of extrafollicular humoral responses in SLE. Overall design: 2 independent datasets; dataset1: total 9 samples (3 subjects, 3 groups, 3 replicates); dataset2: total 20 samples, 2 samples(PD1POS, Tfh) from each of 10 SLE patients
Publication Title
A CD4<sup>+</sup> T cell population expanded in lupus blood provides B cell help through interleukin-10 and succinate.
Sample Metadata Fields
Specimen part, Disease, Treatment, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- NextSeq 500
Description
A better understanding of the mechanisms involved in human plasma cell differentiation will accelerate therapeutic target identification in autoantibody-mediated diseases such as Systemic Lupus Erythematosus (SLE). Here, we describe a novel CXCR5- CXCR3+ PD1hi CD4+ T cell 'helper' population distinct from follicular helper T cells (Tfh) and expanded in blood and inflamed kidneys of SLE patients. Upon activation, these cells express IFN??and high levels of IL10. Additionally, they accumulate high amounts of mitochondrial ROS (mtROS) as the result of reverse electron transport (RET) fueled by succinate. These cells provide potent help to B cells through the synergistic effect of IL10 and succinate. Cells with similar phenotype and function are generated in vitro upon priming naïve CD4+ T cells with oxidized mitochondrial DNA (Ox mtDNA)-activated plasmacytoid dendritic cells (pDCs) in a PD1-dependent manner. Our results provide a novel mechanism for the initiation and/or perpetuation of extrafollicular humoral responses in SLE. Overall design: 9 total samples; 3 groups of 3 biological replicates: control group Th0, co-culture group CpGA-pDC, and co-culture group Ox mtDNA-pDC
Publication Title
A CD4<sup>+</sup> T cell population expanded in lupus blood provides B cell help through interleukin-10 and succinate.
Sample Metadata Fields
Specimen part, Subject
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