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Lidia Cocho, Veronica Martinez, Maria-Jesus J. Gonzalez, Itziar Fernández, Carmen García-Vázquez, Michael E Stern, Margarita Calonge, Amalia Enriquez-De-Salamanca; Molecular Biomarkers in Ocular Graft vs Host Disease (GVHD)-Associated Dry Eye (DE). Invest. Ophthalmol. Vis. Sci. 2014;55(13):2020.
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To measure a panel of tear cytokines/chemokines and mRNA expression of inflammatory molecules in conjunctival epithelial cells in graft vs host disease (GVHD)-associated dry-eye (DE) patients and to correlate them with clinical features.
Ten GVHD-DE patients and 10 age and sex-related controls were evaluated. Patients were medically controlled and had discontinued eyedrops (except artificial tears) 7 days prior evaluation. OSDI questionnaire and clinical tests (conjunctival hyperemia, corneal and conjunctival staining, Schirmer test and tear break-up time) were performed. Unstimulated tears (1 ul) were collected from most symptomatic eye. Levels of EGF, IL-1RA, IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IP-10/CXCL10, eotaxin 1/CCL11, IFN-γ, VEGF, TNF-α and RANTES were measured by multiplex bead assay and correlated with clinical parameters. Upper-bulbar conjunctival epithelial cells were collected by impression cytology and gene expression of 84 inflammatory molecules was determined by qRT2-PCR.
EGF, IL-2 and IP-10/CXCL10 tear levels were decreased in GVHD-DE patients compared to controls (p=0.0009, p=0.028 and p=0.0002, respectively), whereas IFN-γ and IL-12p70 tear levels were increased (p=0.013 and p=0.014). In GVHD-DE patients IL-12p70 tear levels correlated positively with fluorescein corneal staining (rho=0.719, IC=0.1603, 0.9651) and negatively with Schirmer test score (rho=-0.7438, IC=-0.961,-0.1367). IP-10 showed a negative correlation with hyperemia (rho=-0.6005, IC=-0.9057,-0.0478). IFN-γ and IL-1RA levels correlated negatively with Schirmer test score (rho=-0.7438, IC=-0.961,-0.1367, and rho=-0.6781, IC=-0.9608,-0.1115, respectively). Thirty three out of the 84 genes analyzed in conjunctival epithelial cells had statistically significant different expression: IFN-γ, CCL18, IL-9, and CCL2 were highly increased (>15 fold), 26 genes were moderately upregulated (4-15 fold), whereas EGFR mRNA was downregulated (3.36 fold), all in GVHD-DE samples compared to controls.
Several molecules have shown to be increased and decreased in tears of GVHD-DE patients and to be differently expressed in conjunctival epithelial cells. Particularly EGF/EGFR and IFN-γ seem the most relevant molecules/genes to focus on in future studies. These results add further knowledge to the search for potential biomarkers in GVHD-DE.
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