Glucocorticoid Receptor-α and MKP-1 as Candidate Biomarkers for Treatment Response and Disease Activity in Vogt-Koyanagi-Harada Disease
Date
2019
Type:
Article
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Journal Title
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Volume Title
Publisher
Elsevier Inc
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Abstract
Purpose
To investigate the potential of utilizing the expression of genes for glucocorticoid receptor (GR) and mitogen-activated protein kinase phosphatase-1 (MKP-1) as biomarkers of corticosteroid (CS) refractoriness and disease activity in patients with Vogt-Koyanagi-Harada (VKH) disease.
Design
Prospective cohort study.
Methods
Twenty VKH patients receiving their first cycle of CS treatment in the absence of additional systemic immunosuppressive therapy and a control group of fifteen healthy volunteers were recruited from the University of Chile (Santiago, Chile) and US National Institutes of Health (Bethesda, United States). Intraocular inflammation was clinically quantified at enrolment and all follow-up visits. CS refractoriness was defined as an ocular reactivation of VKH upon CS withdrawal at a daily oral prednisone dose of 10 mg or more. Quantitative Reverse transcription polymerase chain reaction (qRT-PCR) was performed to measure the mRNA levels of the alpha (α) and beta (β) isoforms of GR and MKP-1 in peripheral blood mononuclear cells (PBMC) after in vitro stimulation with either anti-CD3/anti-CD28 antibodies, lipopolysaccharide (LPS), or phytohemagglutinin (PHA), in the presence or absence of dexamethasone (Dex).
Results
After 6 hours of stimulation in the presence of Dex, PBMC from CS-refractory VKH patients had an impaired elevation in GRα expression (P = .03). Furthermore, inactive patients showed a significant Dex-induced upregulation of MKP-1 (P = .005).
Conclusions
In this pilot study, the expression of GR isoforms and MKP-1 corresponded with patients' clinical response to systemic CS treatment and disease activity, respectively. Hence, these candidate biomarkers have potential clinical utility in the early identification of CS refractoriness and subclinical inflammation in patients with VKH disease.
Description
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Citation
American Journal of Ophthalmology Volume 207, November 2019, Pages 319-325
Keywords
Vogt-Koyanagi-Harada Disease, Glucocorticoid Receptor-α, Glucocorticoid Receptor-α