Abstract：
OBJECTIVE: Stevens-Johnson syndrome (SJS) is characterised as an immuno-inflammatory condition with potentially blinding ocular sequelae. Therefore, we have investigated the ocular surface immune cell profile and correlated it with secreted tear molecular factors and clinical ocular sequelae in SJS patients.
METHODS: 21 patients (42 eyes) with chronic ocular SJS and 16 healthy controls (20 eyes) were included in the study. Severity, types of keratopathies and ocular surface (OS) manifestations were determined. OS wash samples from study subjects were used to determine the status of 13 immune cell subsets using flow cytometry. Levels of 42 secreted immuno-inflammatory factors were measured by flow cytometry-based multiplex ELISA in tear samples.
RESULTS: Neutrophils (Total, activated), neutrophils/NK cells ratio, neutrophils/T cells ratio were significantly (p < 0.05) elevated in SJS, while, proportions of T cells and NKT cells were significantly lower in SJS patients. Positive association between neutrophils and chronic ocular surface complication score (COCS) was observed, whereas, a negative association was noted between NK cells and COCS. Tear fluid levels of IL-6, IL-8, IL-18, IFNα/β/γ, TNFα, LIF, IL-8, HGF, sTNFR-I, NGAL, Granzyme, Perforins, MMP9/TIMP1 ratio were significantly higher in SJS. Loss of Limbal niche correlated significantly with immune profile and clinical sequelae. Increased neutrophils, decreased NK cells and specific set of altered secreted immuno-inflammatory mediators including bFGF, and IL-8 were observed in SJS patients with different types of keratopathies compared to those without keratopathy.
CONCLUSIONS: Distinct ocular surface immune profile variations were observed to correlate with clinical stages of chronic ocular SJS. Our findings uncover novel mechanisms and potential for targeted therapy in chronic ocular SJS patients.
METHODS: 21 patients (42 eyes) with chronic ocular SJS and 16 healthy controls (20 eyes) were included in the study. Severity, types of keratopathies and ocular surface (OS) manifestations were determined. OS wash samples from study subjects were used to determine the status of 13 immune cell subsets using flow cytometry. Levels of 42 secreted immuno-inflammatory factors were measured by flow cytometry-based multiplex ELISA in tear samples.
RESULTS: Neutrophils (Total, activated), neutrophils/NK cells ratio, neutrophils/T cells ratio were significantly (p < 0.05) elevated in SJS, while, proportions of T cells and NKT cells were significantly lower in SJS patients. Positive association between neutrophils and chronic ocular surface complication score (COCS) was observed, whereas, a negative association was noted between NK cells and COCS. Tear fluid levels of IL-6, IL-8, IL-18, IFNα/β/γ, TNFα, LIF, IL-8, HGF, sTNFR-I, NGAL, Granzyme, Perforins, MMP9/TIMP1 ratio were significantly higher in SJS. Loss of Limbal niche correlated significantly with immune profile and clinical sequelae. Increased neutrophils, decreased NK cells and specific set of altered secreted immuno-inflammatory mediators including bFGF, and IL-8 were observed in SJS patients with different types of keratopathies compared to those without keratopathy.
CONCLUSIONS: Distinct ocular surface immune profile variations were observed to correlate with clinical stages of chronic ocular SJS. Our findings uncover novel mechanisms and potential for targeted therapy in chronic ocular SJS patients.
摘要：
目的：Stevens-Johnson综合征（SJS）的特征是具有潜在致盲性眼部后遗症的免疫炎症状态。因此,我们研究了SJS患者的眼表免疫细胞谱，并将其与分泌的泪液分子因子和临床眼部后遗症相关联。
方法：研究包括21例慢性眼部SJS患者（42只眼）和16例健康对照（20只眼）。严重性,确定了角膜病变的类型和眼表（OS）表现。来自研究对象的OS洗涤样品用于使用流式细胞术确定13个免疫细胞亚群的状态。通过基于流式细胞术的多重ELISA测量泪液样品中42种分泌的免疫炎症因子的水平。
结果：中性粒细胞（总计，激活),中性粒细胞/NK细胞比率，中性粒细胞/T细胞比率在SJS中显著升高（p<0.05），while,SJS患者的T细胞和NKT细胞比例明显降低。中性粒细胞与慢性眼表并发症评分（COCS）呈正相关，然而,NK细胞和COCS之间呈负相关.泪液中IL-6、IL-8、IL-18、IFNα/β/γ、TNFα,LIF,IL-8,HGF,sTNFR-I,NGAL,粒酶,穿孔虫,MMP9/TIMP1比值在SJS中显著较高。角膜缘生态位的丧失与免疫状况和临床后遗症显着相关。中性粒细胞增多,减少的NK细胞和特定的一组改变的分泌的免疫炎症介质，包括bFGF，与没有角膜病变的SJS患者相比，在患有不同类型角膜病变的SJS患者中观察到IL-8。
结论：观察到明显的眼表免疫谱变异与慢性眼部SJS的临床分期相关。我们的发现揭示了慢性眼部SJS患者靶向治疗的新机制和潜力。
方法：研究包括21例慢性眼部SJS患者（42只眼）和16例健康对照（20只眼）。严重性,确定了角膜病变的类型和眼表（OS）表现。来自研究对象的OS洗涤样品用于使用流式细胞术确定13个免疫细胞亚群的状态。通过基于流式细胞术的多重ELISA测量泪液样品中42种分泌的免疫炎症因子的水平。
结果：中性粒细胞（总计，激活),中性粒细胞/NK细胞比率，中性粒细胞/T细胞比率在SJS中显著升高（p<0.05），while,SJS患者的T细胞和NKT细胞比例明显降低。中性粒细胞与慢性眼表并发症评分（COCS）呈正相关，然而,NK细胞和COCS之间呈负相关.泪液中IL-6、IL-8、IL-18、IFNα/β/γ、TNFα,LIF,IL-8,HGF,sTNFR-I,NGAL,粒酶,穿孔虫,MMP9/TIMP1比值在SJS中显著较高。角膜缘生态位的丧失与免疫状况和临床后遗症显着相关。中性粒细胞增多,减少的NK细胞和特定的一组改变的分泌的免疫炎症介质，包括bFGF，与没有角膜病变的SJS患者相比，在患有不同类型角膜病变的SJS患者中观察到IL-8。
结论：观察到明显的眼表免疫谱变异与慢性眼部SJS的临床分期相关。我们的发现揭示了慢性眼部SJS患者靶向治疗的新机制和潜力。
