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.