Expression of miRNAs in serum and PBMCs of patients with Vogt-Koyanagi-Disease as a novel biomarker for the classification of intraocular inflammatory status

Abstract

Purpose : The success of the appraisal of Vogt-Koyanagi-Harada disease (VKH) depends almost exclusively on the experience and expertise of the clinician, thus the non-specialist ophthalmologist could be supported with the development of new objective tests that can be unequivocally interpreted. MicroRNAs (miRNAs) are small RNA molecules that modulate immune function and can promote or prevent inflammation in immune-mediated diseases, therefore, they might provide useful information regarding disease activity in VKH patients. The aim of this work is to determine the association of the expression levels of certain miRNAs in serum and peripheral blood mononuclear cells (PBMCs) with the intraocular inflammatory status in VKH patients.

Methods : Study design: Multicenter, cross-sectional, comparative. Total RNA was isolated from serum and PBMCs from 30 patients with active or inactive VKH disease, and 15 healthy controls. An array of 17 miRNAs were selected for quantification, 15 of which were detected in PBMC and 14 in serum. The expression levels of miRNAs were determined by qPCR in both sample types. Fold-change values were calculated by normalization against the control group using the ΔΔCt method.

Results : The expression levels of miR-23a and miR-126 were higher in the serum of patients with active VKH compared to patients with inactive disease (p-value 0.0341 and 0.0458, respectively). Both serum miRNAs showed overall good performance in the classification of disease activity. The AUC of ROC curve of miR-23a was 0.7917 (sensitivity 91.67%, specificity 53.33% and p-value 0.0104), which was slightly higher than AUC of ROC curve of miR-126 (AUC 0.7857, sensitivity 91.67%, specificity 57.14% and p-value 0.0136). No differences were detected among groups in PBMCs.

Conclusions : Increased expression of miR-23a and miR-126 in serum is associated with active disease among VKH patients. These miRNAs have the potential to be biomarkers of intraocular inflammatory activity and to constitute a novel tool for VKH appraisal that provides objective and unequivocal results.

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