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Hong Liang, Karima Kessal, Ghislaine Rabut, Philippe Daull, Jean-Sebastien Garrigue, Mylène DOCQUIER, Stéphane MELIK PARSADANIANTZ, Françoise Brignole-Baudouin, Christophe Baudouin; Correlations of mRNA expression profiles with clinical symptoms and signs in conjunctival imprints from Sjögren’s syndrome patients. Invest. Ophthalmol. Vis. Sci. 2017;58(8):480.
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© ARVO (1962-2015); The Authors (2016-present)
In dry eye disease, symptoms and signs are not always correlated. The aim of this study was to characterize the expressions of inflammation-related genes on the ocular surface of Sjögren’s syndrome (SS) patients and to evaluate which of them could be correlated with clinical symptoms and signs.
The study was conducted on 30 patients with SS dry eye patients and 15 healthy controls. A set of clinical signs and symptoms were evaluated using the ocular surface disease index (OSDI) questionnaire, corneal fluorescein staining (CFS), tear breakup time (TBUT), Schirmer's test and tear osmolarity. Conjunctival superficial cells were collected by impression cytology and total RNAs were extracted and the transcripts were analyzed using nCounter® human inflammation code set of 249 genes (NanoString technologies). The fold change of mean with a cut off ≥1.5 and <0.8 was chosen to select the differentially expressed genes in the two groups. Mann-Whitney non-parametric statistical test was used, and p<0.05 was considered as statistically significant. A Spearman correlation was performed to correlate the up and down regulated genes with the clinical exams.
Twenty-seven genes were up-regulated and 13 were down-regulated with significant fold changes ranging from 16.7 to 1.5 and 0.8 to 0.3 respectively. OSDI and CFS were the most significantly correlated with 21 and 19 inflammatory genes, respectively. More interestingly, among all the up-regulated genes, 12 genes including IL-6, CCL24, CCL22, CCL5, CCR1, C2, C1QB, CFB, STAT1, CXCR4, LY96, and HLA-DRA were positively correlated with both OSDI and CFS. Two down-regulated genes (GNGT1, HSPB2) were negatively correlated with OSDI and CFS. CXCL2, CXCL9, CXCL10, NOS2, NOX1, MAFF and NOD2 were correlated exclusively with OSDI, and CCL4, TNF, IL-15, ITGB2 and HLA-DRB1, only with CFS. IL1RN was the only gene positively correlated with the Schirmer test. Furthermore, no gene was found correlated with T-BUT or tears osmolarity.
These results highlight the relationship between the expressed inflammatory genes and the patient’s symptoms and signs, assessed with OSDI and CFS respectively. The analysis of inflammatory genes implicated in SS-associated dry eye could be an important tool to determine a pathophysiological profile potentially usable as a biomarker of the disease.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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