Glucocorticoid Receptor-α and MKP-1 as Candidate Biomarkers for Treatment Response and Disease Activity in Vogt-Koyanagi-Harada Disease

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dc.contributor.authorUrzúa, Cristhian
dc.contributor.authorChen, Ping
dc.contributor.authorChaigne-Delalande, Benjamin
dc.contributor.authorLiu, Baoying
dc.contributor.authorAnguita, Rodrigo
dc.contributor.authorGuerrero, Julia
dc.contributor.authorSabat, Pablo
dc.contributor.authorVelásquez, Víctor
dc.contributor.authorSen, Nida
dc.contributor.authorLee, Richard
dc.contributor.authorGoecke, Annelise
dc.date.accessioned2020-09-07T19:39:34Z
dc.date.available2020-09-07T19:39:34Z
dc.date.issued2019
dc.description.abstractPurpose 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.es
dc.identifier.citationAmerican Journal of Ophthalmology Volume 207, November 2019, Pages 319-325es
dc.identifier.urihttps://doi.org/10.1016/j.ajo.2019.06.032es
dc.identifier.urihttp://hdl.handle.net/11447/3417
dc.language.isoenes
dc.publisherElsevier Inces
dc.subjectVogt-Koyanagi-Harada Diseasees
dc.subjectGlucocorticoid Receptor-αes
dc.subjectGlucocorticoid Receptor-αes
dc.titleGlucocorticoid Receptor-α and MKP-1 as Candidate Biomarkers for Treatment Response and Disease Activity in Vogt-Koyanagi-Harada Diseasees
dc.typeArticlees

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