Glucocorticoid Receptor and IL-10 Expression as Biomarkers of Response to Corticosteroids Treatment in Patients With Uveitis

Abstract

Purpose : The use of systemic corticosteroids (CS), has been the mainstay of the treatment for different types of uveitis, including Vogt-Koyanagi-Harada (VKH) disease-associated uveitis. Previous studies suggested the change in expression of Glucocorticoid Receptor (GR) isoforms as potential biomarkers to the early identification of CS-refractory patients with VKH. The mitogen-activated protein kinase phosphatase-1 (MKP-1), has been described as the mediator of the anti-inflammatory effects of CS. The aim of this work was to evaluate the expression levels of, GRa, MKP-1, cytokines and related microRNAs as biomarkers of response to treatment to CS in patients with idiopathic and VKH disease-associated uveitis.

Methods : Prospective cohort study. We assayed blood samples from 19 patients with idiopathic and VKH disease-associated uveitis. The cohort was divided into refractory (n= 11) and sensitive (n= 8) patients, considering the clinical response to corticosteroids (prednisone 60mg/day). The patients underwent 3 blood draws (at 0, 7 and 14 days of treatment), from which the mononuclear cells (PBMC) were isolated by the ficoll method. The expression levels of GRa, MKP-1, cytokines (IL–6, IL-10, IL–17A and TNF–α) and related miRNAs (miR-21 and miR-101) were measured by real-time PCR.

Results : The expression levels of the MKP-1 and cytokines IL-6, IL-17A and TNF-α did not show significant changes on the different days of treatment. However, GRa expression levels at 14 days of treatment were significantly higher in patients refractory to CS therapy (p-value 0.0200) whereas expression levels of IL-10 were significantly lower in the same group (p-value 0.013). The ratio GRa/IL-10 was significatively higher in refractory patients (p-value 0.0078) and the ROC curve analysis for GRa/IL-10 gave a sensitivity of 90.0% and a specificity of 75.0% with an AUC of 0.8375 (p-value 0.0164) for the diagnosis of refractoriness to treatment. No significant differences were found in the expression of miR-21 and miR-101 obtained from PBMC in sensitive and refractory patients.

Conclusions : The evaluation of the expression of GRa and IL-10 and their ratio (GRa/IL-10) after 14 days of treatment with CS appear as promising biomarkers to determine the response to treatment to CS in patients with idiopathic and VKH disease-associated uveitis.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.