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Novel expression signatures identified by transcriptional analysis of separated leukocyte subsets in SLE and vasculitis
Annals of Rheumatic Diseases, 10/22/09

Lyons PA et al. – 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

Methods

44 vasculitis patients, 13 SLE patients and 25 age and sex-matched controls enrolled
CD4 and CD8 T cells, B cells, monocytes and neutrophils 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 identified a substantial number of differentially expressed genes that were not detectable in analysis of PBMC
Analysis of purified T cells identified SLE-associated, CD4 T cell signature consistent with type 1 interferon signalling driving the generation and survival of tissue homing T cells; contributing to disease pathogenesis
Hierarchical clustering using expression data from purified monocytes provided significantly improved discrimination between patient groups than that obtained using PBMC data, presumably because differentially expressed genes reflect genuine differences in processes underlying disease pathogenesis

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