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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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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).
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.
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.
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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