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Gene expression profiling reveals a downregulation in immune-associated genes in patients with AS
  1. Ran Duan,
  2. Paul Leo,
  3. Linda Bradbury,
  4. Matthew A Brown,
  5. Gethin Thomas
  1. Diamantina Institute for Cancer, Immunology & Metabolic Medicine, University of Queensland, Queensland, Australia
  1. Correspondence to Dr Gethin Thomas, Diamantina Institute for Cancer, Immunology & Metabolic Medicine, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, QLD 4102, Australia; gethin.thomas{at}uq.edu.au

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.

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Footnotes

  • Funding We thank the Rebecca L Cooper Medical Research Foundation, the Australian Cancer Research Foundation and Arthritis Australia for funding this project. GT is the recipient of a Lions Medical Research Foundation Senior Research Fellowship, and MB is the recipient of a NHMRC Principal Research Fellowship No 455836.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the University of Queensland Human Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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