May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Microarray Gene Expression Profile of Peripheral Blood From Patients With Sarcoidosis Implicates the Transcription Factor, STAT1
Author Affiliations & Notes
  • S. Pasadhika
    Casey Eye Institute, OHSU, Portland, Oregon
    Chulalongkorn University, Bangkok, Thailand
  • E. D. Crouser
    The Ohio State University Medical Center, Columbus, Ohio
  • C. A. Harrington
    Vaccine & Gene Therapy Institute, OHSU, Portland, Oregon
  • D. Choi
    Public Health & Preventive Medicine, OHSU, Portland, Oregon
  • S. R. Planck
    Casey Eye Institute, OHSU, Portland, Oregon
  • J. R. Smith
    Casey Eye Institute, OHSU, Portland, Oregon
  • J. T. Rosenbaum
    Casey Eye Institute, OHSU, Portland, Oregon
  • Footnotes
    Commercial Relationships  S. Pasadhika, None; E.D. Crouser, None; C.A. Harrington, Dr. Harrington has a fianacial interest in Affymetrix, Inc. This potential conflict of interest has been reviewed and managed by OHSU., I; D. Choi, None; S.R. Planck, None; J.R. Smith, None; J.T. Rosenbaum, None.
  • Footnotes
    Support  NIH Grant EYO15858, HL083830 and Research to Prevent Blindness awards to JTR, JRS, SRP and the CEI
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 4752. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      S. Pasadhika, E. D. Crouser, C. A. Harrington, D. Choi, S. R. Planck, J. R. Smith, J. T. Rosenbaum; Microarray Gene Expression Profile of Peripheral Blood From Patients With Sarcoidosis Implicates the Transcription Factor, STAT1. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4752. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: : Sarcoidosis is an immune-mediated disease that has the potential to affect multiple organs. Uveitis is the most common sight-threatening ocular manifestation. Although both genetic and environmental factors are implicated, the etiology remains unknown. This study tested the hypothesis that patients with sarcoidosis have a characteristic peripheral blood mRNA profile.

Methods: : Blood samples were analyzed using high-density human GeneChip® probe arrays (HG-U133 plus 2.0, Affymetrix) for mRNA expression profiling of peripheral blood leukocytes from 12 patients with sarcoidosis (7 with uveitis, and 5 without uveitis) and 12 healthy controls. Differential gene expression between groups was assessed by Significance Analysis of Microarrays (SAM) after normalization. Genes were studied based on gene ontology function, pathway information, and cluster analyses. Validation was obtained by analysis of gene expression in lymph node or lung biopsy (6 sarcoidosis vs 6 controls).

Results: : 1187 genes were upregulated and 1281 were downregulated among patients with sarcoidosis compared to controls with selection criteria of ≥ 1.5 fold ratio and q value ≤ 0.05. There were no significantly upregulated and downregulated genes detected in sarcoidosis with uveitis compared to sarcoidosis without uveitis. A significant upregulation (> 1.5 fold ratio and q value < 0.001) of the gene transcript for the major transcription factor, STAT1, was validated by similar results from various probe sets that detect different segments of the sequence. In addition, 13 out of 18 genes that are known to be directly downstream of STAT1 were significantly upregulated in patients with sarcoidosis; these include CDKN1A, Pim-1, CXCL9, TRH, MT-1, OPRM1, MHC2TA, IRF-1, WARS, PSMB9, CD64, A2M and CCND1. Gene expression in lung and lymph node confirmed upregulation of STAT1 related genes.

Conclusions: : Gene expression in peripheral blood leukocytes from patients with sarcoidosis differs from that of controls. While sarcoidosis markedly affects gene expression in peripheral blood, the clinical manifestation, uveitis, has less of an effect. STAT1, which is regulated by interferons, appears to have an important role in sarcoidosis. This hypothesis is novel, supported by blood and tissue data, and consistent with other reports that indicate that interferons can cause granulomatous disease.

Keywords: gene microarray • gene/expression • uveitis-clinical/animal model 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×