Reduced Levels of Tear Lacritin Are Associated With Corneal Neuropathy in Patients With the Ocular Component of Sjögren's Syndrome.
Reduced Levels of Tear Lacritin Are Associated With Corneal Neuropathy in Patients With the Ocular Component of Sjögren's Syndrome.
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DOI：
10.1167/iovs.16-19309
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发表时间：
2016-10-01
影响因子：
4.4
通讯作者：
McKown RL
中科院分区：
文献类型：
--
作者：
McNamara NA;Ge S;Lee SM;Enghauser AM;Kuehl L;Chen FY;Gallup M;McKown RL
确定内源性泪液蛋白，lacritin水平是否与干燥综合征（SS）患者角膜神经支配改变和干眼严重程度相关。从10个SS和10个年龄匹配的对照组中获得临床数据。采用酶联免疫吸附测定法测定从Schirmer条中提取的总泪液催泪蛋白。采用蛋白质印迹法检测活性催乳素单体（> 25 kDa）、活性催乳素片段（> 12-15 kDa）和非活性组织转氨酶产生的催乳素（≥40 kDa）。体内共聚焦显微镜用于评估神经纤维密度（NFD）和长度（NFL）。采用斯皮尔曼相关分析法检测泪腺催泪素与神经形态学的关系。采用受试者工作特性分析泪液催泪蛋白的诊断性能。SS患者的活性泪液催泪蛋白显著减少（3.72 ± 5.62 [SS] vs 18.17 ± 4.57 ng/100 ng总泪液蛋白[对照组]; P < 0.001），而非活性泪液催泪蛋白增加（84.99% ± 11.15% [SS] vs 51.04% ± 12.03% [对照组]; P < 0.001）。神经纤维密度（21.70 ± 18.93 vs.31.80 ± 9.35; P = 0.03）和NFL（4.18 ± 3.44 vs.6.54 ± 2.47; P < 0.05）在SS患者中较对照组显著降低。NFL（r = 0.74，P < 0.01）和NFD（r = 0.70，P < 0.01）的降低与泪液催乳素的降低高度相关。同样，总泪液催乳素与Schirmers（r = 0.77，P < 0.01）、眼染色（r =-0.80，P < 0.01）和角膜敏感性（r = 0.81，P < 0.01）高度相关。与传统的SS临床测量相比，泪液催泪蛋白显示出等同或更好的诊断性能（100.00%灵敏度，85.71%特异性，临界值= 14.50 ng/100 ng泪液蛋白）。SS患者泪液催泪蛋白水平的降低与干眼症的临床体征以及NFD和NFL的降低高度相关。Lacritin及其组分在SS中提供了极好的诊断敏感性和特异性。
To determine whether levels of endogenous tear protein, lacritin, are linked to altered corneal innervation and dry eye severity in patients with Sjögren's syndrome (SS). Clinical data were obtained from 10 SS and 10 age-matched controls. Enzyme-linked immunosorbent assay was used to assess total tear lacritin extracted from Schirmer strips. Western blot was used to detect active lacritin monomer (∼25 kDa), active lacritin fragment (∼12–15 kDa), and inactive tissue transglutaminase–generated lacritin (≥40 kDa). In vivo confocal microscopy was used to assess nerve fiber density (NFD) and length (NFL). Relationships between nerve morphology and tear lacritin were examined by Spearman correlation. Diagnostic performance of tear lacritin was analyzed using receiver operating characteristic. Active tear lacritin was significantly reduced in SS patients (3.72 ± 5.62 [SS] versus 18.17 ± 4.57 ng/100 ng total tear protein [controls]; P < 0.001), while inactive lacritin was increased (84.99% ± 11.15% [SS] versus 51.04% ± 12.03% [controls]; P < 0.001). Nerve fiber density (21.70 ± 18.93 vs. 31.80 ± 9.35; P = 0.03) and NFL (4.18 ± 3.44 vs. 6.54 ± 2.47; P < 0.05) were significantly decreased in SS patients compared to controls. Reduced NFL (r = 0.74, P < 0.01) and NFD (r = 0.70, P < 0.01) were highly correlated with reduced tear lacritin. Similarly, total tear lacritin was highly correlated with Schirmers (r = 0.77, P < 0.01), ocular staining (r = −0.80, P < 0.01), and corneal sensitivity (r = 0.81, P < 0.01). Tear lacritin showed equivalent or better diagnostic performance compared to traditional clinical measures for SS (100.00% sensitivity, 85.71% specificity, cutoff = 14.50 ng/100 ng tear protein). Reduced tear lacritin levels in SS patients are highly correlated with clinical signs of dry eye, as well as decreased NFD and NFL. Lacritin and its components provide excellent diagnostic sensitivity and specificity in SS.
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