关键词： inflammatory bowel diseases   gut microbiota   Nod2   NLRs   innate immunity   adaptive immunity   immune-microbe interactions  

摘要： The aetiology and pathogenesis of inflammatory bowel disease (IBD) remains unclear but involves a complex interplay between genetic risk, environmental exposures, the immune system and the gut microbiota. Nearly two decades ago, the first susceptibility gene for Crohn's disease, NOD2, was identified within the IBD 1 locus. Since then, over 230 genetic risk loci have been associated with IBD and yet NOD2 remains the strongest association to date. As an intracellular innate immune sensor of bacteria, investigations into host-microbe interactions, involving both innate and adaptive immune responses, have become of particular interest in understanding the pathogenesis of IBD. Advancements in sequencing technology have lead to the groundbreaking characterization of the gut microbiota and its role in health and disease. While an altered microbiome has been described for IBD, whether it is a cause or an effect of the intestinal inflammation has yet to be determined. Moreover, the bidirectional relationship between the gut microbiota and the mucosal immune system adds to the multifaceted complexity of intestinal homeostasis. A better understanding of how host genetics, including NOD2, influence immune-microbe interactions and alter susceptibility to IBD is necessary in order to develop therapeutic and preventative treatments.

关键词： Inflammatory bowel disease   Crohn's disease   Ulcerative colitis   Killer immunoglobulin-like receptors   Natural killer cell   Meta-analysis   SNP  

摘要： Inflammatory bowel disease (IBD) is a chronic inflammatory disease, which involves the gut and comprises of Crohn's disease (CD) and ulcerative colitis (UC). Immune cells, including natural killer (NK) cells, play an important role in the pathogenesis of the disease. Killer immunoglobulin-like receptors (KIRs) are NK cell surface receptors, which ligate to the class I major histocompatibility complex (MHC) and have inhibitory or activating effects on the NK cells. The aim of this study was to perform a meta-analysis of the six studies evaluating the association in the polymorphisms of these KIR genes and the IBD risk (4 UC and 5 CD studies). A systematic search was conducted in the electronic databases to find all the studies on the KIR gene polymorphism in IBD patients prior to December 2017. The odds ratio (OR) and 95% confidence interval (CI) were used to find any association between KIR gene polymorphisms and the IBD risk. Following extraction of the data from the studies, which were screened by inclusion and exclusion criteria, collectively 432 patients and 886 controls for UC and 1677 patients and 1308 controls for CD were included in the meta-analysis. The statistical evaluation demonstrated positive associations between 2DL5 (OR=1.31, 95% CI=1.01-1.69) and 2DS1 (OR=1.33, 95% CI=1.01-1.76) members of KIR genes and UC risk, as well a negative association between 2DS3 gene and CD risk was detected (OR=0.74, 95% CI=0.60-0.90). There are positive associations between 2DL5 and 2DS1 members of KIR genes and UC risk and a negative association between 2DS3 and CD risk.

摘要： The article discusses the efficacy of the therapeutic strategy of targeting integrins in the gastrointestinal system for the treatment of inflammatory bowel diseases (IBDs). Topics discussed include findings with regard to animal models, specific targeting of the alpha-4-beta-7 integrin protein by the drug vedolizumab and efficacy of the drug in maintaining remission in ulcerative colitis and Crohn's disease.

关键词： INFLAMMATORY bowel diseases   CANCER   INFLAMMATION   IMMUNOSUPPRESSION   T cells  

摘要： Background: Risk benefit strategies in managing inflammatory bowel diseases (IBD) are dependent upon understanding the risks of uncontrolled inflammation vs those of treatments. Malignancy and mortality in IBD have been associated with disease-related inflammation and immune suppression, but data are limited due to their rare occurrence. Aim: To identify and describe the most common causes of mortality, types of cancer and previous or current therapy among children and young adults with paediatric-onset IBD. Methods: Information on paediatric-onset IBD patients diagnosed with malignancy or mortality was prospectively collected via a survey in 25 countries over a 42-month period. Patients were included if death or malignancy occurred after IBD diagnosis but before the age of 26years. Results: In total, 60 patients were identified including 43 malignancies and 26 fatal cases (9 due to cancer). Main causes of fatality were malignancies (n=9), IBD or IBD-therapy related nonmalignant causes (n=10;including 5 infections), and suicides (n=3). Three cases, all fatal, of hepatosplenic T-cell lymphoma were identified, all were biologic-naive but thiopurine-exposed. No other haematological malignancies were fatal. The 6 other fatal cancer cases included 3 colorectal adenocarcinomas and 3 cholangiocarcinomas (CCAs). Primary sclerosing cholangitis (PSC) was present in 5 (56%) fatal cancers (1 colorectal carcinoma, 3 CCAs and 1 hepatosplenic T-cell lymphoma). Conclusions: We report the largest number of paediatric-onset IBD patients with cancer and/or fatal outcomes to date. Malignancies followed by infections were the major causes of mortality. We identified PSC as a significant risk factor for cancer-associated mortality. Disease-related adenocarcinomas were a commoner cause of death than lymphomas.