Utrecht University Medical Center, Utrecht, The Netherlands.
Utrecht University Medical Center and Wilhelmina Children's Hospital, Utrecht, The Netherlands.
Arthritis Rheumatol. 2016 Jul;68(7):1769-79. doi: 10.1002/art.39621.
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.
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.
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.
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.
儿童葡萄膜炎是一种常见于幼年特发性关节炎（JIA）的威胁视力的炎症性眼病。其发病机制尚不清楚，这使得临床管理具有挑战性。我们分析了 JIA 相关葡萄膜炎和常见儿童葡萄膜炎患者眼内液（房水[AqH]）和血清中的可溶性介质，以确定潜在的生物标志物，并研究这种威胁视力的眼病的眼内微环境。
通过多重免疫分析法分析了 73 例 AqH（n=73）和 66 例配对血清（n=66）样本中的 51 种炎症可溶性介质。将 21 例 JIA 相关葡萄膜炎患儿与 15 例无关节炎的慢性前葡萄膜炎患儿、29 例非传染性特发性葡萄膜炎患儿和 8 例非炎症性疾病患儿（对照组）进行比较。为了可视化多个介质的联合效应，我们使用了放射坐标可视化（Radviz）方法。还确定了最佳生物标志物水平截断值。
JIA 相关葡萄膜炎患者 AqH 样本中的白细胞介素-29（IL-29）/干扰素-λ1（IFNλ1）水平降低（P<0.001），潜伏相关肽和骨保护素水平升高（P=0.002 和 P=0.001），但血清中没有。在纠正疾病活动度和治疗的多变量分析中，与特发性葡萄膜炎患者相比，JIA 相关葡萄膜炎患者的眼内 IL-29/IFNλ1 水平确实降低。实际上，JIA 相关葡萄膜炎患者和特发性葡萄膜炎患者的眼内可溶性介质表现出明显不同的特征。IL-29/IFNλ1 具有较高的曲线下面积值（0.954），23.5pg/ml 为最佳截断值。
我们将 IL-29/IFNλ1 鉴定为 JIA 相关葡萄膜炎的眼内生物标志物，这表明异常的 IFNλ 信号可能在 JIA 相关葡萄膜炎中很重要，与其他形式的儿童葡萄膜炎不同。
