J Rheum Dis.  2016 Dec;23(6):363-372. 10.4078/jrd.2016.23.6.363.

Gene Expression Profile in Patients with Axial Spondyloarthritis: Meta-analysis of Publicly Accessible Microarray Datasets

• Park R
• Kim TH
• Ji JD

• KMID: 2364690
• DOI: http://doi.org/10.4078/jrd.2016.23.6.363

Abstract

OBJECTIVE
To identify a gene expression signature in axial spondyloarthritis/ankylosing spondylitis (SpA/AS) and genomic pathways likely to be involved in pathogenesis of SpA/AS patients.
METHODS
Four publicly accessible microarray studies from SpA/AS patients were integrated, and a transcriptomic and network-based meta-analysis was performed. This meta-analysis was compared with a published microarray study in whole blood of AS patients.
RESULTS
According to our meta-analysis, 1,798 genes were differentially expressed in the whole blood of SpA/AS patients compared to healthy controls, while 674 genes were differentially expressed in the synovium of SpA/AS patients compared to healthy controls. When the whole blood meta-analysis data was compared with a published microarray study that also analyzed whole blood in SpA/AS patients, pathways involved in Toll-like receptor signaling, osteoclast differentiation, T cell receptor signaling and janus kinase-signal transducer and activator of transcription (Jak-STAT) signaling were often enriched in SpA/AS. On the other hand, eomesodermin, RUNX3, and interleukin-7 receptor (IL7R) were usually decreased in SpA/AS patients, suggesting that deficiency of these genes contributes to increased IL-17 production in AS.
CONCLUSION
Several common enrichment pathways including Toll-like receptor signaling pathway, osteoclast differentiation, T cell receptor signaling pathway and Jak-STAT signaling pathway were identified in the differentially expressed genes of whole blood and synovium from SpA/AS patients, suggesting that these pathways are involved in the pathogenesis of SpA/AS.

Keyword

Axial spondyloarthritis; Ankylosing spondylitis; Microarray; Network analysis

MeSH Terms

Dataset*
Gene Expression*
Genes, vif
Hand
Humans
Interleukin-17
Interleukin-7
Osteoclasts
Receptors, Antigen, T-Cell
Spondylitis
Spondylitis, Ankylosing
Synovial Membrane
Toll-Like Receptors
Transcriptome*
Transducers
Interleukin-17
Interleukin-7
Receptors, Antigen, T-Cell
Toll-Like Receptors

Figure

• 

  Figure 1. Flow chart of selection process for meta-analysis.

• 

  Figure 2. Osteoclast differentiation pathway (Kyoto Encyclopedia of Genes and Genomes [KEGG] PATHWAY map04380) identified as the enriched functional pathway in spondyloarthritis/ankylosing spondylitis (SpA/AS).

• 

  Figure 3. Deficiency of EOMES, RUNX3, and IL7R in whole blood of spondyloarthritis/ankylosing spondylitis (SpA/AS) patients may be able to induce the increased production of IL-17. IL7R: interleukin-7 receptor, EOMES: eomesodermin.  

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