Profiling of genes expressed in peripheral blood mononuclear cells predicts glucocorticoid sensitivity in asthma patients
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Bjornsdottir, Unnur S
Gudmundsdottir, Asta S
Adalsteinsdottir, Asdis E
Gulcher, Jeffrey R
MetadataShow full item record
CitationProc. Natl. Acad. Sci. U.S.A.. 2005, 102(41):14789-94
AbstractGene expression profiles were examined in freshly isolated peripheral blood mononuclear cells (PBMC) from two independent cohorts (training and test sets) of glucocorticoid (GC)-sensitive (n = 64) and GC-resistant (n = 42) asthma patients in search of genes that accurately predict responders and nonresponders to inhaled corticosteroids. A total of 11,812 genes were examined with high-density oligonucleotide microarrays in both resting PBMC (106 patients) and cells treated in vitro with IL-1beta and TNF-alpha combined (88 patients), with or without GC. A total of 5,011 genes were expressed at significant levels in the PBMC, and 1,334 of those were notably up-regulated or down-regulated by IL-1beta/TNF-alpha treatment. The expression changes of 923 genes were significantly reversed in GC responders in the presence of GC. The expression pattern of 15 of these 923 genes that most accurately separated GC responders (n = 26) from the nonresponders (n = 18) in the training set, based on the weighted voting algorithm, predicted the independent test set of equal size with 84% accuracy. The expression accuracy of these genes was confirmed by real-time-quantitative PCR, wherein 11 of the 15 genes predicted GC sensitivity at baseline with 84% accuracy, with one gene predicting at 81% in an independent cohort of 79 patients. We conclude that we have uncovered gene expression profiles in PBMC that predict clinical response to inhaled GC therapy with meaningful accuracy. Upon validation in an independent study, these results support the development of a diagnostic test to guide GC therapy in asthma patients.
DescriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links field
- Using peripheral blood mononuclear cells to determine a gene expression profile of acute ischemic stroke: a pilot investigation.
- Authors: Moore DF, Li H, Jeffries N, Wright V, Cooper RA Jr, Elkahloun A, Gelderman MP, Zudaire E, Blevins G, Yu H, Goldin E, Baird AE
- Issue date: 2005 Jan 18
- Messenger ribonucleic acid expression profile in peripheral blood cells from RA patients following treatment with an anti-TNF-alpha monoclonal antibody, infliximab.
- Authors: Sekiguchi N, Kawauchi S, Furuya T, Inaba N, Matsuda K, Ando S, Ogasawara M, Aburatani H, Kameda H, Amano K, Abe T, Ito S, Takeuchi T
- Issue date: 2008 Jun
- Expression profiling of genes related to asthma exacerbations.
- Authors: Aoki T, Matsumoto Y, Hirata K, Ochiai K, Okada M, Ichikawa K, Shibasaki M, Arinami T, Sumazaki R, Noguchi E
- Issue date: 2009 Feb
- Association between IL-1beta/TNF-alpha-induced glucocorticoid-sensitive changes in multiple gene expression and altered responsiveness in airway smooth muscle.
- Authors: Hakonarson H, Halapi E, Whelan R, Gulcher J, Stefansson K, Grunstein MM
- Issue date: 2001 Dec
- Overlapping gene expression profiles in rheumatoid fibroblast-like synoviocytes induced by the proinflammatory cytokines interleukin-1 beta and tumor necrosis factor.
- Authors: Taberner M, Scott KF, Weininger L, Mackay CR, Rolph MS
- Issue date: 2005 Jan