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.
In a retrospective analysis of plasma samples from patients with CD or UC, we associated levels of IgG Fc-glycosylation with disease (compared to controls) and its clinical features. These findings could increase our understanding of mechanisms of CD and UC pathogenesis and be used to develop diagnostics or guide treatment.
We performed high-throughput analysis to compare total plasma N-glycomes of individuals with vs without IBD and to identify patterns associated with disease features and the need for treatment. These profiles might be used in diagnosis and for predicting patients' responses to treatment.
BACKGROUND AND OBJECTIVES:
Although the incidence of pediatric celiac disease (CD) is increasing globally, it is uncertain whether this is attributed to improved case ascertainment or signifies a true rise. We aimed to identify all incident cases of childhood CD in southeast Scotland over the period 1990 to 2009 to assess trends in total incidence and cases diagnosed as a result of (1) a classic presentation, (2) a nonclassic presentation, or (3) targeted screening.
METHODS:
Twenty-year retrospective cohort study of case notes, pathology databases, endoscopy, and patient records for all children (<16 years of age) diagnosed with CD on biopsy in southeast Scotland (at-risk population of 225 000–233 000). Data were age-gender standardized and Poisson regression models used to calculate changes in incidence over time.
RESULTS:
A total of 266 children were diagnosed from 1990 to 2009 with an increase in incidence from 1.8/100 000 (95% confidence interval [CI] 1.1–2.7) to 11.7/100 000 (95% CI 9.8–13.9) between the epochs 1990 to 1994 and 2005 to 2009, respectively (P < .0001). The incidence of nonclassic presentation (children with a monosymptomatic presentation and those with extraintestinal symptoms) and actively screened cases increased by 1566% (P < .05) and 1170% (P < .001) from 1990 to 1999 to 2000 to 2009, respectively. However, a rise in the incidence of Oslo classic cases from 1.51/100 000 (95% CI 0.91–2.38) in 1990 to 1994 to 5.22/100 000 (95% CI 3.98–6.75) in 2005 to 2009 (P < .01) remained evident.
CONCLUSIONS:
The incidence of pediatric CD increased 6.4-fold over the 20 years. This study demonstrates that this rise is significant for classic CD, indicating a true rise in the incidence of pediatric CD.
Anti-TNFs are effective treatments, usually given with thiopurine co-immunosuppression. This study highlights deficiencies in formal documentation of effect and disparity between disease severity scoring tools which need to be addressed to improve ongoing patient care.
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