Unknown,Transcriptomics,Genomics,Proteomics

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Expression data from Gambian children with and without the clinical signs of active trachoma: U133 Plus2.0 array

ABSTRACT: Conjunctival samples from 60 individuals with and without the clinical signs of active trachoma were analysed on the U133 Plus 2.0 arrays. Global transcriptional changes characteristic of disease and infection phenotypes were identified. Two analysis methods found large numbers of differentially regulated genes and the existence of networks of co-expressed genes. There were signatures characteristic of the host defence response with evidence supporting infiltration of various types of leukocytes and activation of innate responses of epithelial cells. Two separate methods could classify disease and infection phenotype based on transcription signatures with 70% accuracy. These results provide an insight into the complexity of the acute response in trachoma but are able to partly explain the biology of trachoma through the identification of pathways and gene expression sets useful to future studies on chlamydial immunopathogenesis. Conjunctival samples from 60 participants were tested on U133 plus 2.0 arrays (40 participants with clinical signs of active trachoma and 20 controls with normal conjunctivas as before). Samples were further sub-divided based on the detection and quantification of ocular Chlamydia trachomatis load by PCR tests. Gene expression was then assessed using differential expression and construction of co-expression networks. The content of the constructed gene lists which were identified as part of a network or differentially expressed were then tested for enrichment using publically available analysis tools to identify biological pathways expressed in the conjunctiva during C. trachomatis infection and disease episodes.

ORGANISM(S): Homo sapiens

SUBMITTER: Martin Holland

PROVIDER: E-GEOD-20436 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Trachoma is a poorly understood immuno-fibrogenic disease process, initiated by Chlamydia trachomatis (Ct). Differences in conjunctival gene expression profiles between Ethiopians with trachomatous trichiasis (with (TTI) and without (TT) inflammation) and controls (NC) were investigated to identify relevant host responses. Tarsal conjunctival swab samples were collected for RNA isolation and Ct PCR. Transcriptome-wide microarray experiments were conducted on 42 samples (TTI 13, TT 15, NC14). Specific results were confirmed using multiplex quantitative RT-PCR for 16 mRNA targets in an independent collection of case-control samples: 386 case-control pairs (TTI 244, TT 142, NC 386). The gene expression profiles of cases were consistent with: squamous metaplasia (Keratins, SPRR), pro-inflammatory cytokine production (IL-1β, CXCL5, S100A7) and tissue remodelling (MMP7, MMP9, MMP12, HAS3). There was no difference in the level of IFNG between cases and controls. However, cases had increased INDO, NOS2A, and IL13RA2 and reduced IL13. Ct was detected in 1/772. Cases show evidence of ongoing inflammation and tissue remodelling, which were more marked where clinical inflammation was also present. Significantly, these processes appear to be active in the absence of current Ct infection. There was limited evidence of a TH1 response (INDO, NOS2A) and no association between a TH2 response and cases. The epithelium appears actively involved in late cicatricial stages of trachoma through production of pro-inflammatory factors (IL-1β, CXCL5, S100A7). Longitudinal studies are needed to investigate which aetiological factors and pathways are associated with progressive scarring and whether simply controlling chlamydial infection will halt progression in people with established cicatricial disease. Case - control study. Conjunctival swab samples were collected from people with trachomatous trichiasis with (TTI) and without (TT) clinically visable inflammation compared to normal controls (C). Total RNA extracted and analysed on the Illumina WG-6 platrom. Additional extensive qRT-PCR work done on a large set of case-control pairs.

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Expression data from Gambian children with and without the clinical signs of active trachoma: U133 Plus2.0 array

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