Multiplex Cytokine Analysis of Aqueous Humor in Juvenile Idiopathic Arthritis-Associated Anterior Uveitis With or Without Secondary Glaucoma.

Dirk Bauer,Maren Kasper,Carsten Heinz,Jörg M Koch,Arnd Heiligenhaus,Karoline Walscheid,Bernd Kirchhof,Philipp S Müther

doi:10.3389/fimmu.2018.00708

Abstract

Patients with juvenile idiopathic arthritis often develop chronic anterior uveitis (JIAU). JIAU patients possess a particularly high risk for developing secondary glaucoma when inflammatory inactivity has been achieved. By using multiplex bead assay analysis, we assessed levels of pro- and anti-inflammatory cytokines, chemokines, or metalloproteinases in the aqueous humor (AH) of patients with clinically inactive JIAU with (JIAUwG) or without secondary glaucoma (JIAUwoG), or from patients with senile cataract as controls. Laser-flare photometry analysis prior to surgery showed no significant differences between JIAUwG or JIAUwoG. Compared with the control group, levels of interleukin-8, matrix metalloproteinase-2, -3, -9, serum amyloid A (SAA), transforming growth factor beta-1, -2, -3 (TGFβ-1, -2, -3), and tumor necrosis factor-alpha in the AH were significantly higher in patients with clinically inactive JIAUwG or JIAUwoG. Samples from JIAwoG patients displayed significantly higher levels of SAA (P < 0.0116) than JIAUwG patients. JIAUwG patients showed an increased level of TGFβ-2 in AH samples compared with JIAUwoG (P < 0.0009). These molecules may contribute to the clinical development of glaucoma in patients with JIAU.

Highlights

11–13% of patients with juvenile idiopathic arthritis eventually develop uveitis (JIAU), too, typically as chronic anterior uveitis with insidious onset, in the absence of redness or pain
Uveitis patients have an increased risk for elevated intraocular pressure (IOP) and uveitic glaucoma (UG), which might be induced by the inflammatory disease, but may result from corticosteroids given as the first treatment approach to reduce ocular inflammation [4]
Age of JIAU subjects with glaucoma (JIAUwG) and JIAU subjects without glaucoma (JIAUwoG) patients did not significantly differ (P = 0.5); both JIAU groups were significantly younger than the control group with senile cataract (P < 0.0001)

Summary

Introduction

11–13% of patients with juvenile idiopathic arthritis eventually develop uveitis (JIAU), too, typically as chronic anterior uveitis with insidious onset, in the absence of redness or pain. Uveitis patients have an increased risk for elevated IOP and uveitic glaucoma (UG), which might be induced by the inflammatory disease, but may result from corticosteroids given as the first treatment approach to reduce ocular inflammation [4]. Changes to the TM include deposition of extracellular matrix (ECM), different composition of ECM protein, and loss of trabecular endothelial cells, eventually leading to reduced phagocytosis and altered protein cleavage [4, 8] Another often described, but not clearly confirmed explanation for increasing IOP is mechanical obstruction of the outflow pathway by cells and debris [4, 8, 9]. It has been shown previously that active inflammation may result in increased uveoscleral outflow rates and reduced aqueous humor (AH) production [10]

Methods

Results

Conclusion