Ocular fluid analysis in children reveals interleukin-29/interferon-λ1 as a biomarker for juvenile idiopathic arthritis associated uveitis

Abstract

OBJECTIVE: Childhood uveitis is a visual-threatening inflammatory eye disease commonly attributed to juvenile idiopathic arthritis (JIA). The pathogenesis is poorly understood, which makes clinical management challenging. We analyzed soluble mediators in ocular fluid (aqueous humor; AqH) and serum of children with JIA associated uveitis (JIA-U) and common childhood uveitis to identify potential biomarkers and investigate the ocular micro-environment of this sight-threatening eye disease. METHODS: AqH (n=73) and paired serum (n=66) samples were analyzed for 51 soluble inflammatory mediators by multiplex immunoassay. Twenty-one children with JIA-U were compared with 15 with chronic anterior uveitis without arthritis (CAU), 29 with non-infectious idiopathic uveitis (IU), and 8 non-inflammatory controls. For visualization of the joint effect of multiple mediators, we exploited the radial coordinate visualization method (Radviz(TM) ). Also, optimal biomarker level cutoffs were determined. RESULTS: The levels of interleukin-29/interferon-λ1 (IL-29/IFN-λ1) were decreased (P<0.001) and the levels of latency associated peptide (LAP) and osteoprotegerin (OPG) were increased (P=0.002, P=0.001 respectively) in AqH of JIA-U, but not in serum. Multivariate analysis correcting for disease activity and treatment revealed that intraocular IL-29/IFN-λ1 levels were specifically decreased in JIA-U compared to IU. Indeed, JIA-U and IU patients showed distinct intraocular soluble mediator profiles. IL-29/IFN-λ1 had high area under the curve values (0.954) with 23.5 pg/mL as the optimal cutoff value. CONCLUSION: We identified IL-29/IFN-λ1 as an intraocular biomarker for JIA-U suggesting that aberrant IFN-λ signaling might be important in JIA-U and distinct from other forms of childhood uveitis. This article is protected by copyright. All rights reserved.