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S. Kawasaki, S. Kawamoto, N. Yokoi, Y. Minesaki, S. Kinoshita, K. Okubo; Up-Regulated Gene Expression in the Conjunctival Epithelium of Patients With Sjögren’s Syndrome . Invest. Ophthalmol. Vis. Sci. 2003;44(13):416.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To shed a light to the pathogenesis of ocular surface abnormalities in patients with Sjögren’s syndrome (SS) by comparing gene expression profiling in conjunctival epithelial cells from normal individuals and SS patients. Methods: 59 subjects (26 SS patients, 3 non-SS dry eye patients, and 30 normal volunteers) were enrolled in the present study. RNA extracted from their conjunctival epithelial cells was subjected to iAFLP, a competitive PCR-based gene expression assay, to measure gene expression in the 59 samples against 931 genes. Data were analyzed by the two-tailed Welch test, two-dimensional clustering analysis, and discriminant analysis. Disease-related genes were identified and the feasibility of gene expression-based diagnosis of SS was examined. Results: Two-dimensional clustering and discriminant analysis clearly distinguished between SS patients and normal subjects. Of 931 genes tested, 34 were significantly up-regulated and 12 were significantly down-regulated in SS (p < 0.05). Up-regulated genes included kallikrein 7 (x 15.8) and small proline-rich protein 2A (x 9.6), markers for the terminal differentiation of epidermis. Also, HLA-DR, IL-6, monokine-induced-by-gamma-interferon, c-fos, fibronectin, amphiregulin, defensin beta 2, and keratin 16, 6b and 6c were significantly up-regulated. Among the 12 down-regulated genes, interferon-gamma receptor 1 was most notable (x 1/27.3). Conclusions: The up-regulated expression of keratin 6 and 16, small proline-rich protein 2A, and kallikrein 7 in the conjunctival epithelium of SS patients suggests an anomalous keratinization pattern. Epithelial thickening may be due to amphiregulin and/or c-fos-stimulated cell cycle progression. The up-regulation of monokine-induced-by-gamma-interferon, HLA-DR, keratin 6b, 6c, and 16 suggests that in SS, interferon-gamma may play an important role in the altered gene expression in the conjunctival epithelium.
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