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Ocular Fluid Analysis in Children Reveals Interleukin‐29/Interferon‐λ1 as a Biomarker for Juvenile Idiopathic Arthritis–Associated Uveitis
Author(s) -
Haasnoot AnneMieke J. W.,
Kuiper Jonas J. W.,
Hiddingh Sanne,
Schellekens Peter A. W. J. F.,
de Jager Wilco,
Imhof Saskia M.,
Radstake Timothy R. D. J.,
de Boer Joke H.
Publication year - 2016
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.39621
Subject(s) - uveitis , medicine , arthritis , biomarker , pathogenesis , immunology , biochemistry , chemistry
Objective Childhood uveitis is a vision‐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 from children with JIA‐associated uveitis and common childhood uveitis to identify potential biomarkers and investigate the ocular microenvironment of this sight‐threatening eye disease. Methods AqH (n = 73) and paired serum (n = 66) samples were analyzed for 51 soluble mediators of inflammation by multiplex immunoassay. Twenty‐one children with JIA‐associated uveitis were compared to 15 children with chronic anterior uveitis without arthritis, 29 children with noninfectious idiopathic uveitis, and 8 children with noninflammatory conditions (controls). For visualization of the joint effect of multiple mediators, we used the radial coordinate visualization (Radviz) method. Optimal biomarker level cutoffs were also determined. Results The levels of interleukin‐29 (IL‐29)/interferon‐λ1 (IFNλ1) were decreased ( P < 0.001) and the levels of latency‐associated peptide and osteoprotegerin were increased ( P = 0.002 and P = 0.001, respectively) in samples of AqH, but not serum, from patients with JIA‐associated uveitis. Multivariate analysis correcting for disease activity and treatment revealed that intraocular levels of IL‐29/IFNλ1 were specifically decreased in patients with JIA‐associated uveitis as compared to those with idiopathic uveitis. Indeed, JIA‐associated uveitis patients and idiopathic uveitis patients showed distinct profiles of intraocular soluble mediators. IL‐29/IFNλ1 showed a high area under the curve value (0.954), with 23.5 pg/ml as the optimal cutoff value. Conclusion We identified IL‐29/IFNλ1 as an intraocular biomarker for JIA‐associated uveitis, which suggests that aberrant IFNλ signaling might be important in JIA‐associated uveitis and distinct from other forms of childhood uveitis.