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Lidia Cocho, Itziar Fernández, Margarita Calonge, Verónica Martínez, María J. González-García, Dolores Caballero, Lucía López-Corral, Carmen García-Vázquez, Lourdes Vázquez, Michael E. Stern, Amalia Enríquez-de-Salamanca; Gene Expression–Based Predictive Models of Graft Versus Host Disease–Associated Dry Eye. Invest. Ophthalmol. Vis. Sci. 2015;56(8):4570-4581. doi: https://doi.org/10.1167/iovs.15-16736.
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© ARVO (1962-2015); The Authors (2016-present)
To develop a predictive model based on inflammatory gene mRNA expression in conjunctival cells of graft versus host disease (GvHD)–associated dry eye (DE) patients, as well as to find meaningful correlations between gene signals and clinical signs.
Twenty GvHD-DE patients and 14 healthy controls were recruited. Patients discontinued medications for 1 week before examination. Dry eye–related symptoms and signs were recorded, and conjunctival epithelial cells were collected by impression cytology after spending 20 minutes under standard conditions within a Controlled Environmental Research Laboratory. Gene expression of inflammatory molecules was determined by polymerase chain reaction, and the results were correlated with clinical signs. Shrinkage discriminant analysis, support vector machine, and k-nearest neighbor classifier methods were used to develop predictive models that were validated considering accuracy, calibration, and discriminant capability.
Out of the 84 genes analyzed, 34 showed significant differences in expression. IL-6, IL-9, CCL24, CCL18, IL-10, IFN-γ, and CCL2 were highly increased (>6-fold); 26 genes were moderately upregulated (2- to 6-fold), whereas EGFR was downregulated (2.63 fold) in GvHD-DE samples. A panel based on EGFR, IL-6, IL-9, and NAMPT had an area under the receiver operating characteristic curve of 0.994, a sensitivity of 100%, and a specificity of 92.9%. EGFR expression correlated negatively with ocular surface damage markers, while IL-6, IL-9, and NAMPT correlated positively with these tests.
EGFR, IL-6, IL-9, and NAMPT have the greatest potential as diagnostic biomarkers, with excellent sensitivity, specificity, and clinical relevance to the ocular surface status of GvHD.
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