36 research outputs found
ILC3 function as a double-edged sword in inflammatory bowel diseases
Inflammatory bowel diseases (IBD), composed mainly of Crohnâs disease (CD) and ulcerative colitis (UC), are strongly implicated in the development of intestinal inflammation lesions. Its exact etiology and pathogenesis are still undetermined. Recently accumulating evidence supports that group 3 innate lymphoid cells (ILC3) are responsible for gastrointestinal mucosal homeostasis through moderate generation of IL-22, IL-17, and GM-CSF in the physiological state. ILC3 contribute to the progression and aggravation of IBD while both IL-22 and IL-17, along with IFN-Îł, are overexpressed by the dysregulation of NCRâ ILC3 or NCR+ ILC3 function and the bias of NCR+ ILC3 towards ILC1 as well as regulatory ILC dysfunction in the pathological state. Herein, we feature the group 3 innate lymphoid cellsâ development, biological function, maintenance of gut homeostasis, mediation of IBD occurrence, and potential application to IBD therapy
Systematic meta-analyses and field synopsis of genetic and epigenetic studies in paediatric inflammatory bowel disease
We provide a comprehensive field synopsis of genetic and epigenetic associations for paediatric Inflammatory Bowel Disease (IBD). A systematic review was performed and included 84 genetic association studies reporting data for 183 polymorphisms in 71 genes. Meta-analyses were conducted for 20 SNPs in 10 genes of paediatric Crohnâs disease (CD) and for 8 SNPs in 5 genes of paediatric ulcerative colitis (UC). Five epigenetic studies were also included, but formal meta-analysis was not possible. Venice criteria and Bayesian false discovery probability test were applied to assess the credibility of associations. Nine SNPs in 4 genes were considered to have highly credible associations with paediatric CD, of which four variants (rs2066847, rs12521868, rs26313667, rs1800629) were not previously identified in paediatric GWAS. Differential DNA methylation in NOD2 and TNF-α, dysregulated expression in let-7 and miR-124 were associated with paediatric IBD, but not as yet replicated. Highly credible SNPs associated with paediatric IBD have also been implicated in adult IBD, with similar magnitudes of associations. Early onset and distinct phenotypic features of paediatric IBD might be due to distinct epigenetic changes, but these findings need to be replicated. Further progress identifying genetic and epigenetic susceptibility of paediatric IBD will require international collaboration, population diversity and harmonization of protocols
MicroRNAs: new players in IBD
MicroRNAs (miRNAs) are small non-coding RNAs, 18â23 nucleotides long, which act as post-transcriptional regulators of gene expression. miRNAs are strongly implicated in the pathogenesis of many common diseases, including IBDs. This review aims to outline the history, biogenesis and regulation of miRNAs. The role of miRNAs in the development and regulation of the innate and adaptive immune system is discussed, with a particular focus on mechanisms pertinent to IBD and the potential translational applications
Comparison of mortality following hospitalisation for ulcerative colitis in Scotland between 1998â2000 and 2007â2009
Background Scottish nationwide linkage data from 1998 to 2000 demonstrated high 3âyear mortality in patients hospitalised with ulcerative colitis (UC). Aim To compare 3âyear mortality, and factors related to mortality, in Scottish patients hospitalised with UC between 1998â2000 and 2007â2009. Methods The Scottish Morbidity Records and linked datasets were used to assess 3âyear mortality, standardised mortality ratio (SMR) and multivariate analyses of factors associated with 3âyear mortality. The 3âyear mortality was determined after four admission types: surgeryâelective or emergency; medicalâelective or emergency. Ageâstandardised mortality rates (ASR) were used to compare mortality rates between periods. Results Ulcerative colitis admissions increased from 10.6 in Period 1 to 11.6 per 100 000 population per year in Period 2 (P = 0.046). Crude and adjusted 3âyear mortality fell between time periods (crude 12.2% to 8.3%; adjusted OR 0.59, CI 0.42â0.81, P = 0.04). Adjusted 3âyear mortality following emergency medical admission (OR 0.58, CI 0.39â0.87, P = 0.003) and in patients >65 years (38.8% to 28.7%, P = 0.02) was lower in Period 2. The SMR in period 1 was 3.04 and 2.96 in Period 2. Directly ageâstandardised mortality decreased from 373 (CI 309â437) to 264 (CI 212â316) per 10 000 personâyears. On multivariate analysis, increasing age (50â64 years OR 7.11 (CI 2.77â18.27, P < 0.05); 65â74 years OR 14.70 (CI 5.65â38.25 P < 0.05); >75 years OR 46.42 (CI 18.29â117.78, P < 0.001) and coâmorbidity (OR 3.02, CI 1.72â5.28, P < 0.001) were significantly associated with 3âyear mortality in Period 2. Conclusions Comparisons of crude and adjusted mortality rates suggest significant improvement in outcome over the last decade â however, mortality remains high, and older age and coâmorbidity are important predictors of outcome
Comparison of mortality following hospitalisation for ulcerative colitis in Scotland between 1998â2000 and 2007â2009
Background
Scottish nationwide linkage data from 1998 to 2000 demonstrated high 3âyear mortality in patients hospitalised with ulcerative colitis (UC).
Aim
To compare 3âyear mortality, and factors related to mortality, in Scottish patients hospitalised with UC between 1998â2000 and 2007â2009.
Methods
The Scottish Morbidity Records and linked datasets were used to assess 3âyear mortality, standardised mortality ratio (SMR) and multivariate analyses of factors associated with 3âyear mortality. The 3âyear mortality was determined after four admission types: surgeryâelective or emergency; medicalâelective or emergency.
Ageâstandardised mortality rates (ASR) were used to compare mortality rates between periods.
Results
Ulcerative colitis admissions increased from 10.6 in Period 1 to 11.6 per 100 000 population per year in Period 2 (P = 0.046). Crude and adjusted 3âyear mortality fell between time periods (crude 12.2% to 8.3%; adjusted OR 0.59, CI 0.42â0.81, P = 0.04). Adjusted 3âyear mortality following emergency medical admission (OR 0.58, CI 0.39â0.87, P = 0.003) and in patients >65 years (38.8% to 28.7%, P = 0.02) was lower in Period 2. The SMR in period 1 was 3.04 and 2.96 in Period 2. Directly ageâstandardised mortality decreased from 373 (CI 309â437) to 264 (CI 212â316) per 10 000 personâyears. On multivariate analysis, increasing age (50â64 years OR 7.11 (CI 2.77â18.27, P 75 years OR 46.42 (CI 18.29â117.78, P < 0.001) and coâmorbidity (OR 3.02, CI 1.72â5.28, P < 0.001) were significantly associated with 3âyear mortality in Period 2.
Conclusions
Comparisons of crude and adjusted mortality rates suggest significant improvement in outcome over the last decade â however, mortality remains high, and older age and coâmorbidity are important predictors of outcome