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M. J. Burton, S. N. Rajak, E. Habtamu, D. C. Mabey, R. L. Bailey; Immuno-Fibrogenic Responses in Trachomatous Conjunctival Scarring: A Case-Control Study. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5359.
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Trachoma, the leading infectious cause of blindness worldwide, is a cicatrising conjunctivitis driven by Chlamydia trachomatis. The immuno-fibrogenic responses involved are poorly understood, which is limiting efforts to develop a vaccine. The purpose of this study was to investigate the major features of the immune response in scarring trachoma by gene expression analysis.
In this study from Ethiopia, individuals with trachomatous trichiasis (TT) were compared to normal controls (NC). Conjunctival swab samples were collected for RNA isolation. Total RNA was extracted. Transcriptone-wide analysis was performed by microarray (WG-6, Illumina) on a limited sub-set of cases and controls. The relative expression levels of various genes of interest indentified by microarray were measured by Real-time RT-PCR.
772 people were recruited (386 TT, 386 NC). Microarray experiments were performed on 14NC and 28TT. 4423 genes were regulated at the adj. p<0.001 level. Pathway analysis (GeneGo) found activation of proteolytic pathways and inflammatory cascades. There was extensive evidence of transformation to a keratinised epithelium. Real-time PCR was performed for 16 genes on the full 772 CC set. TT cases had upregulation of Psoriasin (S100A7), IL-1b, IL-19, NOS2A, MMP7, MMP9, MMP12, HAS3, INDO and CXCL5.There was no difference in the expression of INFg while IL-13 was lower in TT.
Trachomatous trichiasis was associated with a pro-inflammatory response (S100A7, IL-1b, CXCL5) in the conjunctiva and evidence of altered connective tissue regulation (MMP7, MMP9, MMP12, HAS3). There was evidence of a predominantly TH1 response (INDO raised, IL-13 lower, IL-13RA raised) and classical macrophage activation (NOS2A).
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