Arafat Samer N, Robert Marie-Claude, Abud Tulio, Spurr-Michaud Sandra, Amparo Francisco, Dohlman Claes H, Dana Reza, Gipson Ilene K
Schepens Eye Research Institute-Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts; Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
Schepens Eye Research Institute-Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts; Department of Ophthalmology and Visual Sciences, Paulista School of Medicine, Federal University of Sao Paulo-UNIFESP, Sao Paulo, Brazil.
Am J Ophthalmol. 2017 Apr;176:46-52. doi: 10.1016/j.ajo.2016.12.026. Epub 2017 Jan 8.
To investigate the levels of neutrophil elastase (NE), matrix metalloproteinases (MMPs), and myeloperoxidase (MPO) in tear washes of patients with ocular graft-vs-host disease (oGVHD).
Case-control study.
Based on established criteria, oGVHD patients (n = 14; 28 eyes) and age-/sex-matched healthy controls (n = 14; 28 eyes) were enrolled. Tear washes were collected and analyzed for NE using a single-analyte enzyme-linked immunosorbent assay (ELISA). MMPs (1, 2, 3, 7, 8, 9, 12), MPO, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 were analyzed using multianalyte bead-based ELISA assays. Total MMP activity was measured using a fluorimetric assay. Correlation studies were performed between NE, MMP-8, MMP-9, and MPO within study groups.
NE, MMP-8, MMP-9, and MPO levels were elevated in oGVHD tears when compared with controls (P < .0001). NE was the most elevated analyte. MMP activity was higher and TIMP-1 levels were lower in oGVHD than in control (P < .0001). In oGVHD, NE significantly correlated with MMP-8 (r = 0.92), MMP-9 (r = 0.90), and MPO (r = 0.79) (P < .0001). MMP-8 correlated with MMP-9 (r = 0.96, P < .0001), and MPO (r = 0.60, P = .001). MMP-9 correlated with MPO (r = 0.55, P = .002). In controls, NE, MMP-9, and MPO significantly correlated with each other (P < .0001).
The marked increase in NE in oGVHD tears that correlated strongly with elevated MMP-8, MMP-9, and MPO suggests a common neutrophilic source and provides evidence of neutrophil activity on the ocular surface of oGVHD patients.
研究眼部移植物抗宿主病（oGVHD）患者泪液冲洗液中中性粒细胞弹性蛋白酶（NE）、基质金属蛋白酶（MMPs）和髓过氧化物酶（MPO）的水平。
病例对照研究。
根据既定标准，纳入oGVHD患者（n = 14；28只眼）和年龄/性别匹配的健康对照者（n = 14；28只眼）。收集泪液冲洗液，使用单分析物酶联免疫吸附测定（ELISA）分析NE。使用基于多分析物微珠的ELISA测定法分析MMPs（1、2、3、7、8、9、12）、MPO和基质金属蛋白酶组织抑制剂（TIMP）-1。使用荧光测定法测量总MMP活性。在研究组内进行NE、MMP-8、MMP-9和MPO之间的相关性研究。
与对照组相比，oGVHD泪液中NE、MMP-8、MMP-9和MPO水平升高（P <.0001）。NE是升高最明显的分析物。oGVHD患者的MMP活性高于对照组，TIMP-1水平低于对照组（P <.0001）。在oGVHD中，NE与MMP-8（r = 0.92）、MMP-9（r = 0.90）和MPO（r = 0.79）显著相关（P <.0001）。MMP-8与MMP-9（r = 0.96，P <.0001）和MPO（r = 0.60，P =.001）相关。MMP-9与MPO（r = 0.55，P =.002）相关。在对照组中，NE、MMP-9和MPO彼此显著相关（P <.0001）。
oGVHD泪液中NE显著增加，且与升高的MMP-8、MMP-9和MPO密切相关，提示存在共同的中性粒细胞来源，并为oGVHD患者眼表的中性粒细胞活性提供了证据。
