Analysis of Th17-associated cytokines and clinical correlations in patients with dry eye disease

We aimed to investigate the expressions of three Th17-associated cytokines, interleukin (IL)-17A, IL-6 and IL-23, in protein and mRNA levels and their correlations with ocular surface parameters in patients with dry eye disease (DED) through a small sample size case control study. A total of 45 female subjects were divided into Sjögren’s syndrome (SS) DED group, non-Sjögren’s syndrome (non-SS) DED group and control group. Ocular surface disease index (OSDI) was self-answered and clinical tests including tear-film breakup time (BUT), Schirmer I test, cornea fluorescein staining (CFS) were performed. The conjunctival mRNA expressions of these cytokines were investigated by real-time polymerase chain reaction (PCR) and the levels of protein in tears were measured by mutiplex bead analysis. The correlations between cytokines and ocular surface parameters were analyzed. Results show that the expressions of IL-17A and IL-6 in protein and mRNA levels were both significantly increased in the DED group (P0.05) and no correlation found between the IL-23 and any ocular surface parameter (P>0.05). These findings indicates that the three Th17-associated cytokines, IL-17A, IL-6 and IL-23, play roles in the pathogenesis of DED and the expressions of IL-17A and IL-6 in tears have potential to be diagnostic biomarkers for DED.

本研究旨在通过小样本病例对照研究，探讨三种Th17相关细胞因子——白细胞介素（interleukin，IL）-17A、IL-6及IL-23的蛋白与mRNA表达水平，并分析其与干眼病（dry eye disease，DED）患者眼表参数的相关性。本研究共纳入45名女性受试者，分为干燥综合征（Sjögren’s syndrome，SS）相关性DED组、非干燥综合征（non-Sjögren’s syndrome，non-SS）相关性DED组及对照组。所有受试者完成眼表疾病指数（ocular surface disease index，OSDI）自评量表，并接受泪膜破裂时间（tear-film breakup time，BUT）、施墨I试验、角膜荧光素染色（cornea fluorescein staining，CFS）等临床检查。本研究采用实时荧光定量聚合酶链反应（real-time polymerase chain reaction，PCR）检测受试者结膜组织中上述细胞因子的mRNA表达水平，通过多重微球免疫分析法测定泪液中各细胞因子的蛋白浓度，并分析细胞因子表达水平与眼表参数的相关性。研究结果显示，DED组患者泪液及结膜组织中IL-17A与IL-6的蛋白及mRNA表达水平均显著升高（P<0.05）；IL-23的表达水平与所有眼表参数均无显著相关性（P>0.05）。本研究结果表明，IL-17A、IL-6及IL-23这三种Th17相关细胞因子均参与了干眼病的发病过程，且泪液中IL-17A与IL-6的表达水平有望成为干眼病潜在的诊断生物标志物。