Danish cohort of monozygotic inflammatory bowel disease twins:Clinical characteristics and inflammatory activity

To describe the establishment of a Danish inflammatory bowel diseases (IBD) twin cohort with focus on concordance of treatment and inflammatory markers.We identified MZ twins, likely to be discordant or concordant for IBD, by merging information from the Danish Twin Register and the National Patient Register. The twins were asked to provide biological samples, questionnaires, and data access to patient files and public registries. Biological samples were collected via a mobile laboratory, which allowed for immediate centrifugation, fractionation, and storage of samples. The mean time from collection of samples to storage in the -80 °C mobile freezer was less than one hour. The diagnoses where validated using the Copenhagen diagnostic criteria.We identified 159 MZ IBD twin pairs, in a total of 62 (39%) pairs both twins agreed to participate. Of the supposed 62 IBD pairs, the IBD diagnosis could be confirmed in 54 pairs. The cohort included 10 concordant pairs, whereof some were discordant for either treatment or surgery. The 10 concordant pairs, where both pairs suffered from IBD, included eight CD/CD pairs, one UC/UC pair and one UC/IBDU pair. The discordant pairs comprised 31 UC, 5 IBDU (IBD unclassified), and 8 CD discordant pairs. In the co-twins not affected by IBD, calprotectin was above 100 μg/g in 2 participants, and above 50 μg/g in a further 5 participants.The presented IBD twin cohorts are an excellent resource for bioinformatics studies with proper adjustment for disease-associated exposures including medication and inflammatory activity in the co-twins

Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 2: Current management

info:eu-repo/semantics/publishedVersio

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text

Investigation of acute inflammation in Crohn's disease and chronic granulomatous disease

Neutrophil function is defective in Crohn's disease and chronic granulomatous disease (CGD). Patients with CGD develop a colitis that is indistinguishable from Crohn's disease. In order to develop a model to assess treatment strategies, colitis was studied in CGD mice. CGD mice did not develop colitis spontaneously. Colitis induced by dextran sodium sulphate augmented with human faecal flora produced self-limiting chronic inflammation. Chronic colitis did develop after oral administration of Diclofenac. Crystals developed in the lungs of CGD mice. They were shown to be composed of the protein Yml. This was located in neutrophil granules and gastric epithelial cells and demonstrated to have weak -hexosaminidase activity. In order to investigate inflammation in Crohn's disease, a method was developed to induce acute inflammation in humans using cantharidin blisters. Neutrophil migration into blisters was reduced in Crohn's disease, independent of blister fluid chemoldnes and cytokines. The respiratory burst of blister fluid macrophages was increased in Crohn's disease after stimulation with opsonised bacteria. Neutrophils isolated from venous blood of Crohn's disease patients demonstrated normal oxygen consumption. Digestion of radiolabelled bacteria by neutrophils was assessed in a small number of Crohn's disease patients and found to be normal. Experimental evidence suggested haploinsufficiency of p47phox as a possible cause of Crohn's disease. DNA from patients with inflammatory bowel disease was screened for this mutation. No excess in the p47phox haplotype was found. However, reduction in the p47phox gene to p47phox -pseudogene ratio was associated with Crohn's disease. Augmentation of neutrophil function by Granulocyte Colony Stimulating Factor (G- CSF) was assessed in Crohn's disease. Serum G-CSF was raised slightly in Crohn's disease. Two days G-CSF administration in vivo caused a reduction in venous neutrophil oxygen consumption and enhanced neutrophil penetration of cantharidin blisters, equally in control and Crohn's disease subjects. Therapy with G-CSF for one month may have improved the clinical condition of a minority of patients with Crohn's disease