Epigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide DNA methylation differences in 240 newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) and 5 differentially methylated regions (DMRs), which we study in detail using whole genome bisulphite sequencing. We replicate the top DMP (RPS6KA2) and DMRs (VMP1, ITGB2 and TXK) in an independent cohort. Using paired genetic and epigenetic data, we delineate methylation quantitative trait loci; VMP1/microRNA-21 methylation associates with two polymorphisms in linkage disequilibrium with a known IBD susceptibility variant. Separated cell data shows that IBD-associated hypermethylation within the TXK promoter region negatively correlates with gene expression in whole-blood and CD8+ T cells, but not other cell types. Thus, site-specific DNA methylation changes in IBD relate to underlying genotype and associate with cell-specific alteration in gene expression.

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A radiofrequency air plasma has been used to incorporate new functionalities at the surface of cycloolefin polymers (Zeonex and Topas), polymethyl methacrylate (PMMA), styrene-acrylonitrile copolymer (SAN), and polystyrene (PS). The main goals with the plasma treatment of the different plastics were to hydrophilize the surfaces and to provide good cell culture properties. Surfaces treated at high RF power/gas flow ratios (50 to 100 W/sccm) became highly hydrophilic (water contact angles of about 5 degrees) and stable towards washing in 70% (v/v) ethanol. Those treated at lower power/gas flow ratios (3 to 10 W/sccm) were less hydrophilic and not wash-stable. Cell growth properties of HeLa cervix carcinoma cells as good as on commercial tissue-culture polystyrene could be obtained for Zeonex, SAN, and PS, treated at relatively low RF power/ gas flow ratios. However, no untreated plastics were suitable for culturing these cells. XPS spectra features show that ester, ether/alcohol, and ester/carboxyl groups are formed during the plasma treatments of the different plastics. Measurable amounts of carboxylic acid carbon after plasma treatment were only observed for PS and Topas. Furthermore, at high RF power/gas flow ratios fluorine, aluminium and silicon were incorporated in all investigated plastics surfaces due to ablation-deposition processes in the reaction chamber.

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Background Success in personalised medicine in complex disease is critically dependent on biomarker discovery. We profiled serum proteins using a novel proximity extension assay (PEA) to identify diagnostic and prognostic biomarkers in inflammatory bowel disease (IBD). Methods We conducted a prospective case-control study in an inception cohort of 552 patients (328 IBD, 224 non-IBD), profiling proteins recruited across 6 centres. Treatment escalation was characterised by the need for biological agents or surgery after initial disease remission. Nested leave-one-out cross validation was used to examine the performance of diagnostic and prognostic proteins. Results A total of 66 serum proteins differentiated IBD from symptomatic non-IBD controls including MMP-12 (Holm adjusted p=4.1×10 -23 ) and OSM (p=3.7×10 -16). Nine of these proteins associate with cis- germline variation (59 independent SNPs). Fifteen proteins, all members of TNF independent pathways including IL-1 and OSM predicted escalation, over a median follow-up of 518 (IQR 224-756) days. Nested cross-validation of the entire data set allows characterisation of 5-protein-models (96% comprising five core proteins ITGAV, EpCAM, IL18, SLAMF7, and IL8) which define a high-risk subgroup in IBD (HR 3.90, CI: 2.43-6.26), or allows distinct 2, and 3 protein models for UC and CD respectively. Conclusion We have characterised a simple oligo-protein panel that has the potential to identify IBD from symptomatic controls and to predict future disease course. Further prospective work is required to validate our findings.