Gene expression profiling reveals a downregulation in immune-associated genes in patients with AS

Duan, R., Leo, P., Bradbury, L., Brown, Matthew A, & Thomas, G. (2010) Gene expression profiling reveals a downregulation in immune-associated genes in patients with AS. Annals of the Rheumatic Diseases, 69(9), pp. 1724-1729.

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Abstract

Objective:

To identify differentially expressed genes in peripheral blood mononuclear cells (PBMCs) from patients with ankylosing spondylitis (AS) compared with healthy individuals.

Methods:

RNA was extracted from PBMCs collected from 18 patients with active disease and 18 gender-matched and age-matched controls. Expression profiles of these cells were determined using microarray. Candidate genes with differential expressions were confirmed in the same samples using quantitative reverse transcription-PCR (qRT-PCR). These genes were then validated in a different sample cohort of 35 patients with AS and 18 controls by qRT-PCR.

Results:

Microarray analysis identified 452 genes detected with 485 probes which were differentially expressed between patients with AS and controls. Underexpression of NR4A2, tumour necrosis factor AIP3 (TNFAIP3) and CD69 was confirmed. These genes were further validated in a different sample group in which the patients with AS had a wider range of disease activity. Predictive algorithms were also developed from the expression data using receiver-operating characteristic curves, which demonstrated that the three candidate genes have ∼80% power to predict AS according to their expression levels.

Conclusions:

The findings show differences in global gene expression patterns between patients with AS and controls, suggesting an immunosuppressive phenotype in the patients. Furthermore, downregulated expression of three immune-related genes was confirmed. These candidate genes were also shown to be strong predictive markers for AS.

Impact and interest:

20 citations in Scopus
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19 citations in Web of Science®

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ID Code: 87736
Item Type: Journal Article
Refereed: Yes
Additional Information: No file attached.
Keywords: CD69 antigen, protein tnfaip 3, tumor necrosis factor alpha, unclassified drug, ankylosing spondylitis, article, clinical article, disease activity, down regulation, female, gene expression, human, male, microarray analysis, peripheral blood mononuclear cell, priority journal, reverse transcription polymerase chain reaction, RNA extraction, Adolescent, Adult, Aged, Blood Proteins, Case-Control Studies, Cluster Analysis, Down-Regulation, Gene Expression Profiling, Humans, Leukocytes, Mononuclear, Middle Aged, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction, Spondylitis, Ankylosing
DOI: 10.1136/ard.2009.111690
ISSN: 0003-4967
Divisions: Current > Schools > School of Biomedical Sciences
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 25 Sep 2015 00:15
Last Modified: 22 Aug 2016 02:39

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