Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human separated leukocyte subsets in SLE and vasculitis

ABSTRACT: Objective: To optimize a strategy for identifying gene expression signatures differentiating SLE and anti-neutrophil cytoplasmic antibody-associated vasculitis that provide insight into the pathogenesis and identify biomarkers.
Methods: Forty four vasculitis patients, 13 SLE patients and 25 age and sex-matched controls were enrolled. CD4 and CD8 T cells, B cells, monocytes and neutrophils were isolated from each patient and, together with unseparated peripheral blood mononuclear cells (PBMC), were hybridised to spotted oligonucleotide microarrays.
Results: Using expression data obtained from purified cells we identified a substantial number of differentially expressed genes that were not detectable in the analysis of PBMC. Analysis of purified T cells identified an SLE-associated, CD4 T cell signature consistent with type 1 interferon signalling driving the generation and survival of tissue homing T cells and thereby contributing to disease pathogenesis. Moreover, hierarchical clustering using expression data from purified monocytes provided significantly improved discrimination between the patient groups than that obtained using PBMC data, presumably because the differentially expressed genes reflect genuine differences in processes underlying disease pathogenesis.
Conclusion: The analysis of leucocyte subsets enabled the identification of gene signatures of both pathogenic relevance and with better disease discrimination than those identified in PBMCs. Thus, this approach provides substantial advantages in the search for diagnostic and prognostic biomarkers in autoimmune disease.

ORGANISM(S): Homo sapiens

DISEASE(S): Microscopic Polyangiitis

SUBMITTER: Paul Lyons

PROVIDER: E-MTAB-145 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Novel expression signatures identified by transcriptional analysis of separated leucocyte subsets in systemic lupus erythematosus and vasculitis.

Lyons Paul A PA McKinney Eoin F EF Rayner Tim F TF Hatton Alexander A Woffendin Hayley B HB Koukoulaki Maria M Freeman Thomas C TC Jayne David R W DR Chaudhry Afzal N AN Smith Kenneth G C KG

Annals of the rheumatic diseases 20091007 6

<h4>Objective</h4>To optimise a strategy for identifying gene expression signatures differentiating systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody-associated vasculitis that provide insight into disease pathogenesis and identify biomarkers.<h4>Methods</h4>44 vasculitis patients, 13 SLE patients and 25 age and sex-matched controls were enrolled. CD4 and CD8 T cells, B cells, monocytes and neutrophils were isolated from each patient and, together with unseparated periph ...[more]

PMID: 19815495

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Project description:Objective. Microarray analysis was used to determine whether children with recent onset polyarticular juvenile idiopathic arthritis (JIA) exhibit biologically or clinically informative gene expression signatures in peripheral blood mononuclear cells (PBMC). Methods. Peripheral blood samples were obtained from 59 healthy children and 61 children with polyarticular JIA prior to treatment with second-line medications, such as methotrexate or biological agents. RNA was purified from Ficoll-isolated mononuclear cells, fluorescently labeled and then hybridized to Affymetrix U133 Plus 2.0 GeneChips. Data were analyzed using ANOVA at a 5% false discovery rate threshold after Robust Multi-Array Average pre-processing and Distance Weighted Discrimination normalization. Results. Initial analysis revealed 873 probe sets for genes that were differentially expressed between polyarticular JIA and controls. Hierarchical clustering of these probe sets distinguished three subgroups within polyarticular JIA. Prototypical subjects within each subgroup were identified and used to define subgroup-specific gene expression signatures. One of these signatures was associated with monocyte markers, another with transforming growth factor-beta-inducible genes, and a third with immediate-early genes. Correlation of these gene expression signatures with clinical and biological features of JIA subgroups suggests direct relevance to aspects of disease activity and supports the division of polyarticular JIA into distinct subsets. Conclusions. PBMC gene expression signatures in recent onset polyarticular JIA reflect discrete disease processes and offer a molecular classification of disease. Keywords: Patient vs. control, reassessment of phenotype PBMC samples were obtained from 59 healthy children and 61 children with polyarticular JIA prior to treatment with second-line medications, such as methotrexate or biological agents. RNA was purified from Ficoll-isolated mononuclear cells, fluorescently labeled and then hybridized to Affymetrix U133 Plus 2.0 GeneChips. Data were analyzed using ANOVA at a 5% false discovery rate threshold after Robust Multi-Array Average pre-processing and Distance Weighted Discrimination normalization.

Dataset Information

Transcription profiling of human separated leukocyte subsets in SLE and vasculitis

Publications

Novel expression signatures identified by transcriptional analysis of separated leucocyte subsets in systemic lupus erythematosus and vasculitis.

Similar Datasets

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