泪液乳铁蛋白水平降低与干燥综合征眼部病变患者的角膜神经病变相关。
Reduced Levels of Tear Lacritin Are Associated With Corneal Neuropathy in Patients With the Ocular Component of Sjögren's Syndrome.
作者信息
McNamara Nancy A, Ge Shaokui, Lee Salena M, Enghauser Alison M, Kuehl Lindsey, Chen Feeling Y-T, Gallup Marianne, McKown Robert L
机构信息
School of Optometry and Vision Science Program, University of California-Berkeley, Berkeley, California, United States 2Department of Anatomy, University of California-San Francisco, San Francisco, California, United States.
School of Optometry and Vision Science Program, University of California-Berkeley, Berkeley, California, United States.
出版信息
Invest Ophthalmol Vis Sci. 2016 Oct 1;57(13):5237-5243. doi: 10.1167/iovs.16-19309.
PURPOSE
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).
METHODS
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.
RESULTS
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).
CONCLUSIONS
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.
目的
确定干燥综合征（SS）患者内源性泪液蛋白乳铁蛋白水平是否与角膜神经支配改变及干眼严重程度相关。
方法
获取10例SS患者和10例年龄匹配的对照者的临床资料。采用酶联免疫吸附测定法评估从泪液滤纸条中提取的总泪液乳铁蛋白。采用蛋白质免疫印迹法检测活性乳铁蛋白单体（约25 kDa）、活性乳铁蛋白片段（约12 - 15 kDa）和无活性的组织转谷氨酰胺酶生成的乳铁蛋白（≥40 kDa）。采用共聚焦显微镜活体成像评估神经纤维密度（NFD）和神经纤维长度（NFL）。通过Spearman相关性分析神经形态与泪液乳铁蛋白之间的关系。使用受试者工作特征曲线分析泪液乳铁蛋白的诊断性能。
结果
SS患者的活性泪液乳铁蛋白显著降低（SS组为3.72±5.62，对照组每100 ng总泪液蛋白中为18.17±4.57 ng；P<0.001）而无活性乳铁蛋白增加（SS组为84.99%±11.15%，对照组为51.04%±12.03%；P<0.001）。与对照组相比，SS患者的神经纤维密度（21.70±18.93对31.80±9.35；P = 0.03）和NFL（4.18±3.44对6.54±2.47；P<0.05）显著降低。NFL降低（r = 0.74，P<0.01）和NFD降低（r = 0.70，P<0.01）与泪液乳铁蛋白降低高度相关。同样，总泪液乳铁蛋白与泪液分泌试验（r = 0.77，P<0.01）、眼部染色（r = -0.80，P<0.01）和角膜敏感性（r = 0.81，P<0.01）高度相关。与SS的传统临床指标相比，泪液乳铁蛋白显示出相当或更好的诊断性能（敏感性100.00%，特异性85.71%，临界值 = 14.50 ng/100 ng泪液蛋白）。
结论
SS患者泪液乳铁蛋白水平降低与干眼临床体征以及NFD和NFL降低高度相关。乳铁蛋白及其成分在SS中具有出色的诊断敏感性和特异性。
Zotero 插件