关键词： TUMOR necrosis factor   INFLAMMATORY bowel diseases   ULCERATIVE colitis   HYPERBARIC oxygenation   ARGON plasmas  

关键词： IBD: clinical trials   immunology   microbiology and inflammatory bowel diseases   screening and diagnosis  

摘要： Background and AimProteinase 3 antineutrophil cytoplasmic antibodies (PR3-ANCAs) are well-known serological markers for granulomatosis with polyangiitis, but their role as serological markers for inflammatory bowel disease remains uncertain. The present study aimed to evaluate the diagnostic and clinical role of PR3-ANCAs as markers for inflammatory bowel disease. MethodsUsing a new methodology with chemiluminescence enzyme immunoassay, serum PR3-ANCA titers were assessed in 102 patients with ulcerative colitis (UC), 67 patients with Crohn's disease (CD), 44 controls with other intestinal diseases, and 66 healthy controls. Associations with clinical data were investigated. The diagnostic role of PR3-ANCAs was evaluated by receiver operating characteristic analysis. ResultsProteinase 3 antineutrophil cytoplasmic antibody titers were significantly higher in patients with UC than in those with CD patients, patients with intestinal diseases (intestinal controls), and healthy controls (all P<0.001). Receiver operating characteristic analysis demonstrated an area under the curve of 0.85 (95% confidence interval: 0.83-0.87) and showed that the manufacturer's cutoff value (3.5U/mL) had a sensitivity of 39.2% and specificity of 96.6% for UC. There was a significant difference between PR3-ANCA-positive and PR3-ANCA-negative patients with regard to disease duration (P<0.05) and disease severity (P<0.01). ConclusionsProteinase 3 antineutrophil cytoplasmic antibodies were significantly more prevalent in patients with UC than in those with CD and controls. Our results suggested the role of PR3-ANCAs as serological markers for aiding in diagnosing UC and evaluating disease severity. Further prospective studies are needed across multiple populations of patients and ethnic groups.

关键词： Inflammatory bowel disease   Women   Vaccines   Pregnancy   Breastfeeding  

摘要： About half of all inflammatory bowel disease (IBD) patients are women. It is important that physicians are aware of gender-specific needs women with IBD may have. This review covers general and specific women's health issues related to their IBD. It is intended to be practical and give a brief overview of topics including body image, menstruation, contraception, cervical cancer screening, preconception counseling, anxiety, depression, pregnancy, breastfeeding, menopause, skin exams, vaccines, laboratory monitoring and bone health.

关键词： INFLAMMATORY bowel diseases   MONOCYTES   MACROPHAGES   HOMEOSTASIS   IMMUNOPATHOLOGY   T cells  

摘要： Chronic inflammation in inflammatory bowel disease (IBD) results from a breakdown of intestinal immune homeostasis and compromise of the intestinal barrier. Genome-wide association studies have identified over 200 genetic loci associated with risk for IBD, but the functional mechanisms of most of these genetic variants remain unknown. Polymorphisms at the TNFSF15 locus, which encodes the TNF superfamily cytokine commonly known as TL1A, are associated with susceptibility to IBD in multiple ethnic groups. In a wide variety of murine models of inflammation including models of IBD, TNFSF15 promotes immunopathology by signaling through its receptor DR3. Such evidence has led to the hypothesis that expression of this lymphocyte costimulatory cytokine increases risk for IBD. In contrast, here we show that the IBD-risk haplotype at TNFSF15 is associated with decreased expression of the gene by peripheral blood monocytes in both healthy volunteers and IBD patients. This association persists under various stimulation conditions at both the RNA and protein levels and is maintained after macrophage differentiation. Utilizing a "recall-by-genotype" bioresource for allele-specific expression measurements in a functional fine-mapping assay, we localize the polymorphism controlling TNFSF15 expression to the regulatory region upstream of the gene. Through a T cell costimulation assay, we demonstrate that genetically regulated TNFSF15 has functional relevance. These findings indicate that genetically enhanced expression of TNFSF15 in specific cell types may confer protection against the development of IBD.

关键词： Anti-integrin   Biomarkers   Inflammatory bowel disease   Personalized medicine  

摘要： Background/Aims Vedolizumab is an anti-alpha 4 beta 7 monoclonal antibody approved for the treatment of inflammatory bowel disease (IBD). This exploratory study aimed to identify biomarkers associated with vedolizumab response. Methods Twenty-six IBD patients (15 with Crohn's, 11 with ulcerative or indeterminate colitis) initiating vedolizumab at a single center between 2014 and 2016 underwent sampling of serum and peripheral blood mononuclear cells (PBMCs) before and during vedolizumab therapy. Response was defined as steroid-free improvement in endoscopic score or Harvey-Bradshaw index/simple clinical colitis activity index (reduction greater than 3 or total less than 3). PBMCs were evaluated for immunophenotype and expression of alpha 4 beta 7 integrin on lymphocytes before and during vedolizumab therapy. Serum vedolizumab levels and alpha 4 beta 7 saturation were measured serially after induction. Results Fourteen out of 26 (54%) patients treated with vedolizumab responded to therapy. Pretreatment alpha 4 beta 7 expression was higher in responders on multiple subsets of T, B, and NK cells, with terminal effector memory (p = .0009 for CD4 and .0043 for CD8) and NK cells (p = .0047) best discriminating between responders and nonresponders. During therapy, log(10) serum vedolizumab levels at trough were higher in responders than nonresponders (p = .0007). Conversely, the percentage of effector memory T cells with free alpha 4 beta 7 at trough was lower in responders than nonresponders (p < .0001). However, loss of alpha 4 beta 7 saturation with vedolizumab was more sensitive to low serum vedolizumab in nonresponders. Conclusions Pretreatment alpha 4 beta 7 expression and alpha 4 beta 7 receptor saturation during maintenance therapy were identified as candidate biomarkers for vedolizumab response.

关键词： Crohn's disease   immunolymph   osteoimmunology   therapeutic intervention  

摘要： Inflammatory bowel disease (IBD) is a chronic disease with gastrointestinal dysfunction as well as comorbidities such as inflammation-induced bone loss and impaired immune response. Current treatments for IBD all have negative, potentially severe side effects. We aimed to test whether exogenous treatment with irisin, a novel immunomodulatory adipomyokine, could ameliorate IBD-induced lymphatic and bone alterations. Irisin treatment improved both gut and bone outcomes by mitigating inflammation and restoring structure. In the gut, IBD caused colonic lymphatic hyperproliferation into the mucosal and submucosal compartments. This proliferation in the rodent model is akin to what is observed in IBD patient case studies. In bone, IBD increased osteoclast surface and decreased bone formation. Both gut and osteocytes in bone exhibited elevated levels of TNF- and receptor activator of NF-B ligand (RANKL) protein expression. Exogenous irisin treatment restored normal colonic lymphatic architecture and increased bone formation rate concurrent with decreased osteoclast surfaces. After irisin treatment, gut and osteocyte TNF- and RANKL protein expression levels were no different from vehicle controls. Our data indicate that the systemic immunologic changes that occur in IBD are initiated by damage in the gut and likely linked through the lymphatic system. Additionally, irisin is a potential novel intervention mitigating both local inflammatory changes in the gut and distant changes in ***, S. A., Metzger, C. E., Bloomfield, S. A., Zawieja, D. C. Inflammation-induced lymphatic architecture and bone turnover changes are ameliorated by irisin treatment in chronic inflammatory bowel disease.

关键词： Intestinal Diseases   Depression   Inflammatory Bowel Diseases   Anxiety  

摘要： This article is linked to Stapersma et al papers. To view these articles visit https://***/10.1111/apt.14865 and https://***/10.1111/apt.14928.

关键词： Cardamonin   Inflammatory bowel disease   NLRP3 inflammasome   Aryl hydrocarbon receptor  

摘要： The present study aimed to evaluate the anti-colitis effect and underlying mechanisms of cardamonin, a natural flavone isolated from Alpinia katsumadai Hayata. The results showed that oral cardamonin significantly inhibited dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice, evidenced by improvement of disease activity index scores, myeloperoxidase activity, length shortening and histopathological changes of colons. A rectal administration of cardamonin also exhibited marked anti-colitis effect, suggesting that oral cardamonin might function in a prototype form. Cardamonin down-regulated levels of IL-1 beta, TNF-alpha, IL-6, NLRP3, cleaved caspase-1, ASC, cleaved IL-1 beta in colons of colitis mice. In vitro, cardamonin inhibited NLRP3 inflammasome activation in THP-1 and bone marrow-derived macrophages. It acted as an AhR activator, enhanced dissociation of AhR/HSP90 complexes, association of AhR/ARNT complexes, AhR nuclear translocation, XRE reporter gene activity, and AhR/ARNT/XRE DNA binding activity in THP-1 cells. The AhR antagonist CH223191 obviously abolished NLRP3 inflammasome activation inhibited by cardamonin. Furthermore, cardamonin elevated levels of Nrf2 and its target genes NQO1, Trxl, SOD2, HO-1, and the effect on NQO1 was the most obvious. The relationship of cardamonin-adjusted AhR activation, expressions of Nrf2 and NQO1, and NLRP3 inflammasome activation was confirmed by using CH223191, siAhR, ML385 and siNQO1, respectively. Finally, CH223191 was shown to abolish amelioration of cardamonin on DSS- and TNBS-induced colitis, inhibition of NLRP3 inflammasome activation and up-regulation of Nrf2 and NQO1 levels in colons. Taken together, cardamonin ameliorated colitis in mice through the activation of AhR/Nrf2/NQO1 pathway and consequent inhibition of NLRP3 inflammasome activation.

关键词： Breast Milk   Crohn's Disease   Lactation   Ulcerative Colitis  

摘要： BACKGROUND & AIMS: Exposure to biologic and immunosuppressant agents during breastfeeding is controversial, and there are limited data on safety. We investigated whether biologics are detectable in breast milk from women receiving treatment for inflammatory bowel diseases (IBDs) and whether breastfeeding while receiving treatment is associated with infections or developmental delays. METHODS: We performed a multicenter prospective study of women with IBD and their infants, collecting breast milk samples (n = 72) from patients receiving biologic therapy from October 2013 to November 2015. Drug concentrations were measured in all breast milk samples at several time points within 48 hours of collection and within 168 hours for some samples. Child development was assessed using the Ages and Stages Questionnaire 3, completed by 824 women with IBD (treated or untreated) during pregnancy (620 breastfed, and 204 did not). Data on children's health and development were obtained from mothers and pediatricians, along with information on mothers' medication exposure, IBD history, activity, pregnancy, and postpartum complications. We used chi-squared method or Fisher exact test to determine associations between categorical values and compared differences in continuous outcomes between groups using analysis of variance models. The primary outcome was drug concentration of biologic agents in breast milk (from 72 women) at 1, 12, 24, and 48 hours after dosing and also at 72, 96, 120, and 168 hours for available samples. Secondary outcomes were a range of infant infections and Ages and Stages Questionnaire 3-defined developmental delays among all breastfed infants. RESULTS: We detected infliximab in breast milk samples from 19 of 29 treated women (maximum, 0.74 ug/mL), adalimumab in 2 of 21 treated women (maximum, 0.71 ug/mL), certolizumab in 3 of 13 treated women (maximum, 0.29 ug/mL), natalizumab in 1 of 2 treated women (maximum, 0.46 ug/mL), and ustekinumab in 4 of 6 treated wome

关键词： MICROORGANISMS   INFLAMMATORY bowel diseases   INFLAMMATION   NOROVIRUS diseases   CROHN’S disease  

摘要： The article presents a study which reviews the myriad microbes for their roles in inflammatory bowel disease (IBD) pathogenesis, highlighting the importance of understanding host-microbe interactions. It mentions that environmental factors and intestinal microbiota conspire to induce inflammation in genetically susceptible individuals. It also states that persistent murine norovirus infection induces Crohn’s disease (CD)-like pathologies in the Atg16L1 mutant mice.