Urzua Cristhian A, Guerrero Julia, Gatica Hector, Velasquez Victor, Goecke Annelise
Department of Ophthalmology, School of Medicine, Universidad de Chile, Santiago, Chile 2Physiology Program, School of Medicine, Universidad de Chile, Santiago, Chile 3Uveitis Department, Hospital del Salvador, Santiago, Chile.
Physiology Program, School of Medicine, Universidad de Chile, Santiago, Chile.
Invest Ophthalmol Vis Sci. 2017 Feb 1;58(2):974-980. doi: 10.1167/iovs.16-20783.
This study is aimed to investigate the role of glucocorticoid receptor (GR) isoforms in peripheral blood mononuclear cells (PBMC) as biomarkers of glucocorticoid (GC) resistance and to validate a set of clinical predictive factors in patients with Vogt-Koyanagi-Harada (VKH) disease.
This was a prospective cohort study that included a total of 21 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 (GRα) and beta (GRβ) isoforms at baseline and at 2 weeks after prednisone therapy initiation.
There were no differences between GRα and GRβ levels in GC-sensitive and GC-resistant patients at baseline before treatment initiation. After 2 weeks of prednisone treatment, GC-sensitive patients had a median 5.5-fold increase in levels of GRα, whereas GC-resistant patients had a median 0.7-fold decrease in levels of this isoform (P = 0.003). Similarly, GRβ increased in GC-sensitive patients, in comparison with GR-resistant patients (6.49-fold versus 1.01 fold, respectively, I = 0.04). 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, odds ratio = 21.0; and P = 0.008, odds ratio = 37.8, respectively). However, associations with visual acuity or tinnitus were not confirmed in this study.
The evaluation of clinical predictive factors and determination of the change in expression of GR isoforms as potential biomarkers can contribute to the early identification of GC-resistant patients with VKH.
本研究旨在探讨糖皮质激素受体（GR）亚型在外周血单个核细胞（PBMC）中作为糖皮质激素（GC）抵抗生物标志物的作用，并验证一组Vogt-小柳原田（VKH）病患者的临床预测因素。
这是一项前瞻性队列研究，共纳入21例VKH患者。在基线时进行了全面的眼科评估，记录了任何临床预测因素（视力≤20/200、耳鸣、慢性病和眼底色素脱失）的存在情况。在基线时以及泼尼松治疗开始后2周进行实时定量PCR，以测量GRα和GRβ亚型的mRNA水平。
在开始治疗前的基线时，GC敏感和GC抵抗患者的GRα和GRβ水平无差异。泼尼松治疗2周后，GC敏感患者的GRα水平中位数增加了5.5倍，而GC抵抗患者的该亚型水平中位数下降了0.7倍（P = 0.003）。同样，与GR抵抗患者相比，GC敏感患者的GRβ增加（分别为6.49倍和1.01倍，I = 0.04）。GR亚型的mRNA水平与疾病活动无关。诊断时的眼底色素脱失和慢性病与GC抵抗相关（分别为P = 0.03，比值比 = 21.0；P = 0.008，比值比 = 37.8）。然而，本研究未证实与视力或耳鸣的相关性。
评估临床预测因素以及确定GR亚型表达变化作为潜在生物标志物，有助于早期识别VKH病的GC抵抗患者。
