PURPOSE: To elucidate the pathogenesis of ocular surface abnormalities in patients with Sjögren's syndrome (SS) by comparing global gene expression patterns in conjunctival epithelial cells from normal individuals and SS patients. METHODS: The study population consisted of 56 subjects (26 SS patients and 30 normal volunteers). RNA extracted from their conjunctival epithelial cells was subjected to introduced amplified fragment length polymorphism (iAFLP), a competitive PCR-based gene expression assay, to measure gene expression in the 56 samples against 931 genes. Data were analyzed by 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, and the inflammation-related genes HLA-DR and IL-6. Monokine-induced-by-gamma-interferon, i.e. c-fos, fibronectin, amphiregulin, defensin beta 2, and keratin 16, -6b and -6c were also up-regulated. Among the 12 down-regulated genes, interferon-gamma receptor 1 was most notable (x1/27.3). 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.
PURPOSE: To elucidate the pathogenesis of ocular surface abnormalities in patients with Sjögren's syndrome (SS) by comparing global gene expression patterns in conjunctival epithelial cells from normal individuals and SS patients. METHODS: The study population consisted of 56 subjects (26 SS patients and 30 normal volunteers). RNA extracted from their conjunctival epithelial cells was subjected to introduced amplified fragment length polymorphism (iAFLP), a competitive PCR-based gene expression assay, to measure gene expression in the 56 samples against 931 genes. Data were analyzed by 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, and the inflammation-related genes HLA-DR and IL-6. Monokine-induced-by-gamma-interferon, i.e. c-fos, fibronectin, amphiregulin, defensin beta 2, and keratin 16, -6b and -6c were also up-regulated. Among the 12 down-regulated genes, interferon-gamma receptor 1 was most notable (x1/27.3). 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.
Authors: H Westekemper; G Anastassiou; W Sauerwein; P Chauvel; N Bornfeld; K-P Steuhl; D Meller Journal: Ophthalmologe Date: 2006-07 Impact factor: 1.059
Authors: Srihari Narayanan; Rachel L Redfern; William L Miller; Kelly K Nichols; Alison M McDermott Journal: Ocul Surf Date: 2013-01-29 Impact factor: 5.033
Authors: Stephen C Pflugfelder; Cintia S De Paiva; Quianta L Moore; Eugene A Volpe; De-Quan Li; Koray Gumus; Mahira L Zaheer; Rosa M Corrales Journal: Invest Ophthalmol Vis Sci Date: 2015-11 Impact factor: 4.799