May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Dissecting the Transcriptome of Ankylosing Spondylitis Associated With Uveitis
Author Affiliations & Notes
  • S. M. Sharma
    Ophthalmology, Casey Eye Institute, Portland, Oregon
  • D. Choi
    Public Health Administration, Oregon Health Sciences University, Portland, Oregon
  • J. R. Smith
    Ophthalmology, Casey Eye Institute, Portland, Oregon
  • S. R. Planck
    Ophthalmology, Casey Eye Institute, Portland, Oregon
  • T. M. Martin
    Ophthalmology, Casey Eye Institute, Portland, Oregon
  • C. A. Harrington
    Vaccine and Gene Therapy Institute, Oregon Health Sciences Technology, Portland, Oregon
  • C. R. Austin
    Ophthalmology, Casey Eye Institute, Portland, Oregon
  • J. T. Rosenbaum
    Ophthalmology, Casey Eye Institute, Portland, Oregon
  • Footnotes
    Commercial Relationships  S.M. Sharma, None; D. Choi, None; J.R. Smith, None; S.R. Planck, None; T.M. Martin, None; C.A. Harrington, Dr. Harrington has a significant financial interest in Affymetrix, Inc. This potential conflict of interest has been reviewed and managed by OHSU, I; C.R. Austin, None; J.T. Rosenbaum, None.
  • Footnotes
    Support  NIH grant EY015858, Research to Prevent Blindness Awards to JTR, TMM, SRP and Casey Eye Institute
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 4747. doi:https://doi.org/
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      S. M. Sharma, D. Choi, J. R. Smith, S. R. Planck, T. M. Martin, C. A. Harrington, C. R. Austin, J. T. Rosenbaum; Dissecting the Transcriptome of Ankylosing Spondylitis Associated With Uveitis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4747. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To test the hypothesis that ankylosing spondylitis (AS) is characterized by a distinct pattern of gene expression in peripheral blood and that patients with and without uveitis can be distinguished.

Methods: : High-density human GeneChip® probe arrays (HG-U133 plus 2.0, Affymetrix, Inc.) were used to profile mRNA of peripheral blood leukocytes from 12 patients with AS who were not receiving systemic immunomodulatory therapy. These included 7 patients with active uveitis or a history of uveitis, 5 without uveitis, and 12 unaffected controls. After normalization, differential gene expression between groups was assessed by Significance Analysis of Microarrays (SAM).Differential expression was defined as a 1.5-Fold Change (FC) with a q value < 5%. For specific pathways implicated in this analysis, we also considered transcripts with a FC 1.2-1.5. Cluster analyses, gene ontology and pathway information were studied. Current hypotheses in AS pathogenesis were examined in the context of gene expression.

Results: : There were 556 up-regulated and 1518 down-regulated transcripts in AS patients compared to controls. Up-regulated transcripts included molecules involved in signaling via IL1R, bone remodeling and the TLR4 molecule. Down-regulated functional groups included wnt-catenin pathway members also involved in bone remodeling, apoptosis-related transcripts, and NK cell-related transcripts. Transcription factors bearing the zinc finger C2H2 domain as well as genes regulated by HNF4α were down-regulated, as was ARTS1, a recently recognized gene with polymorphisms influencing susceptibility to AS. Surprisingly transcripts for inflammatory cytokines were down-regulated, including TNFα, IL17, IL6 and IFNγ. Gene expression signatures for AS with uveitis and AS without groups were similar , although AS with uveitis was associated with down-regulation of clusters of molecules bearing common structural motifs such as Src homology 2. TGFβR2 was upregulated within this group. Current etiological hypotheses in AS that were unsupported by our gene expression data were the unfolded protein response and Th17 pathway.

Conclusions: : AS is a complicated disease with multiple interconnected etiologies. IL1 and its receptors may have a role in AS. Bone remodeling factors, the apoptosis pathway and the innate immune system are distinguishable in peripheral blood from patients with AS versus controls.

Keywords: gene microarray • uveitis-clinical/animal model 
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