June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Evaluation of the glucocorticoid receptor as a biomarker of treatment response in Vogt-Koyanagi-Harada disease
Author Affiliations & Notes
  • Cristhian Alejandro Urzua
    Ophthalmology, Universidad de Chile, Santiago, Chile
  • Julia Guerrero
    Universidad de Chile, Santiago, Chile
  • Hector Gatica
    Universidad de Chile, Santiago, Chile
  • Victor Velasquez
    Ophthalmology, Universidad de Chile, Santiago, Chile
  • Annelise Goecke
    Universidad de Chile, Santiago, Chile
  • Footnotes
    Commercial Relationships   Cristhian Urzua, CAU is named inventor on a patent application in Chile (no. 2015-001420) that includes the glucocorticoid receptor as a predictive factor for treatment refractoriness in inflammatory diseases (P); Julia Guerrero, None; Hector Gatica, None; Victor Velasquez, None; Annelise Goecke, AG is named inventor on a patent application in Chile (no. 2015-001420) that includes the glucocorticoid receptor as a predictive factor for treatment refractoriness in inflammatory diseases (P)
  • Footnotes
    Support  FONDECYT, Santiago, Chile (grant number: 1080529).
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 505. doi:
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      Cristhian Alejandro Urzua, Julia Guerrero, Hector Gatica, Victor Velasquez, Annelise Goecke; Evaluation of the glucocorticoid receptor as a biomarker of treatment response in Vogt-Koyanagi-Harada disease
      . Invest. Ophthalmol. Vis. Sci. 2017;58(8):505.

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

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Abstract

Purpose : To investigate the role of glucocorticoid receptor (GR) isoforms in peripheral blood mononuclear cells (PBMC) as a biomarker of glucocorticoid (GC) resistance and to validate a set of clinical predictive factors in patients with Vogt-Koyanagi-Harada disease (VKH).

Methods : Prospective cohort study that included a total of twenty-one patients with VKH. A complete ophthalmologic evaluation was carried out at baseline that recorded the presence of any clinical predictive factors (visual acuity < 20/200, tinnitus, chronic disease and fundus depigmentation). Real-time quantitative PCR was performed to measure the mRNA levels of GR alpha isoform (GRα) and beta isoform (GRβ), at baseline and two weeks after prednisone initiation.

Results : There were no differences between GC-sensitive and GC-resistant patients in GRα and GRβ levels at baseline before treatment initiation. After two weeks of prednisone treatment, GC-sensitive patients had a median 5.5-fold increase in the levels of GRα, while GC-resistant patients had a median 0.7-fold decrease in the levels of this isoform (p=0.003). GRβ expression increased in both groups, with a significantly higher increment in GC-sensitive patients (6.6-fold versus 4.6-fold, p=0.01). The mRNA levels of GR isoforms were independent of disease activity. Fundus depigmentation and chronic disease at diagnosis were associated with GC-resistance (p=0.03, OR=21.0 and p=0.008, OR=37.8, respectively). However, associations with visual acuity or tinnitus were not confirmed in this study.

Conclusions : The evaluation of clinical predictive factors and the determination of the change in expression of GR isoforms as potential biomarkers can contribute to the early identification of GC-resistant patients with VKH.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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