| 1. |
- Ardesjö, Brita, et al.
(författare)
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Identification of a novel staining pattern of bile duct epithelial cells in primary sclerosing cholangitis
- 2010
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Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1078-0998 .- 1536-4844. ; 16:2, s. 305-311
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Primary sclerosing cholangitis (PSC) is an inflammatory disease of the bile ducts with an unknown etiology. A number of autoantigens have been proposed, but an early diagnostic marker is still lacking. Our aim was to identify such an autoantigen. METHODS: Immunostaining was performed on normal human bile duct with sera from patients with PSC and controls. To identify an autoantigen a cDNA library from normal human choledochus was constructed and immunoscreened with patient sera. Using in vitro transcription and translation and immunoprecipitation we examined the immunoreactivity against PDZ domain containing 1 (PDZK1) in 35 patients with PSC, 198 control patients, and 94 healthy controls. RESULTS: We observed a previously unpublished staining pattern in which cytoplasmatic granules and apical cell membranes of biliary epithelial cells were stained by PSC sera. Strong immunoreactivity to these structures was obtained with 12 out of 35 PSC sera (34%) but not with sera from healthy controls. By screening the cDNA library we identified PDZK1 as a candidate antigen. Immunoreactivity against PDZK1 was detected in 9% of PSC patients, 2% of inflammatory bowel disease (IBD) patients, 8% of autoimmune pancreatitis patients, 18% of Grave's disease patients, and 1% of healthy controls. CONCLUSIONS: Previously unpublished, specific, and strong autoantibodies against epithelial cells of the bile duct in PSC sera were identified. Furthermore, PDZK1 is suggested as a potential new autoantigen.
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| 2. |
- Berglund, Martin, et al.
(författare)
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IL-1 receptor-associated kinase M downregulates DSS-induced colitis
- 2010
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Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1078-0998 .- 1536-4844. ; 16:10, s. 1778-1786
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ulcerative colitis is associated with increased colon permeability resulting in bacterial translocation into the lamina propria. We investigate the importance of the Toll-like receptor (TLR) regulating protein IL-1 receptor-associated kinase M (IRAK-M) using the erosive dextran sulfate sodium (DSS)-induced model of colitis. Methods: IRAK-M-competent and -incompetent mice were treated with 3% DSS for 5 days followed by 2 days of regular drinking water. Clinical signs of disease were followed for 7 days. At day 7 the mice were sacrificed and plasma and tissue were collected for histopathological examination and analyses of the production of cytokines and chemokines as well as expression of T-cell transcription factors. Results: At day 7 IRAK-M-deficient mice display a reduced total body weight (77.1 +/- 2.1 versus 88.5 +/- 2.0, *P=0.002) and an increased macroscopical (2.7 +/- 0.2 versus 1.6 +/- 0.1, *P 0.002) and histopathological (6.0 +/- 0 versus 3.3 +/- 60.5, *P < 0.001) colon score compared to wildtype mice. Furthermore, IRAK-M-deficient mice have increased colon mRNA expression of proinflammatory cytokines and increased tumor necrosis factor concentrations (41.1 +/- 13.5 versus 12.8 +/- 2.0 pg/mL, *P = 0.010) in plasma. Conclusions: This is the first report examining the role of IRAK-M in colitis. We find that IRAK-M is of critical importance in downregulating induction and progression of DSS colitis, and thereby suggesting that IRAK-M might be a target for future interventional therapies. (Inflamm Bowel Dis 2010; 16: 1778-1786)
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| 3. |
- Burisch, Johan, et al.
(författare)
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Initial Disease Course and Treatment in an Inflammatory Bowel Disease Inception Cohort in Europe : The ECCO-EpiCom Cohort
- 2014
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Ingår i: Inflammatory Bowel Diseases. - : Lippincott Williams & Wilkins. - 1078-0998 .- 1536-4844. ; 20:1, s. 36-46
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Tidskriftsartikel (refereegranskat)abstract
- Background:The EpiCom cohort is a prospective, population-based, inception cohort of inflammatory bowel disease (IBD) patients from 31 European centers covering a background population of 10.1 million. The aim of this study was to assess the 1-year outcome in the EpiCom cohort.Methods:Patients were followed-up every third month during the first 12 (3) months, and clinical data, demographics, disease activity, medical therapy, surgery, cancers, and deaths were collected and entered in a Web-based database (www.epicom-ecco.eu).Results:In total, 1367 patients were included in the 1-year follow-up. In western Europe, 65 Crohn's disease (CD) (16%), 20 ulcerative colitis (UC) (4%), and 4 IBD unclassified (4%) patients underwent surgery, and in eastern Europe, 12 CD (12%) and 2 UC (1%) patients underwent surgery. Eighty-one CD (20%), 80 UC (14%), and 13 (9%) IBD unclassified patients were hospitalized in western Europe compared with 17 CD (16%) and 12 UC (8%) patients in eastern Europe. The cumulative probability of receiving immunomodulators was 57% for CD in western (median time to treatment 2 months) and 44% (1 month) in eastern Europe, and 21% (5 months) and 5% (6 months) for biological therapy, respectively. For UC patients, the cumulative probability was 22% (4 months) and 15% (3 months) for immunomodulators and 6% (3 months) and 1% (12 months) for biological therapy, respectively in the western and eastern Europe.Discussion:In this cohort, immunological therapy was initiated within the first months of disease. Surgery and hospitalization rates did not differ between patients from eastern and western Europe, although more western European patients received biological agents and were comparable to previous population-based inception cohorts.
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| 4. |
- Chan, Simon S. M., et al.
(författare)
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Carbohydrate Intake in the Etiology of Crohn's Disease and Ulcerative Colitis
- 2014
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Ingår i: Inflammatory Bowel Diseases. - : Lippincott Williams & Wilkins. - 1078-0998 .- 1536-4844. ; 20:11, s. 2013-2021
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diet may have a role in the etiology of inflammatory bowel disease. In previous studies, the associations between increased intakes of carbohydrates, sugar, starch, and inflammatory bowel disease are inconsistent. However, few prospective studies have investigated the associations between these macronutrients and incident Crohn's disease (CD) or ulcerative colitis (UC). Methods: A total of 401,326 men and women were recruited between 1991 and 1998. At recruitment, dietary intakes of carbohydrate, sugar, and starch were measured using validated food frequency questionnaires. The cohort was monitored identifying participants who developed incident CD or UC. Cases were matched with 4 controls, and odds ratios were calculated for quintiles of total carbohydrate, sugar, and starch intakes adjusted for total energy intake, body mass index, and smoking. Results: One hundred ten participants developed CD, and 244 participants developed UC during follow-up. The adjusted odds ratio for the highest versus the lowest quintiles of total carbohydrate intake for CD was 0.87, 95% CI = 0.24 to 3.12 and for UC 1.46, 95% CI = 0.62 to 3.46, with no significant trends across quintiles for either (CD, P-trend = 0.70; UC, P-trend = 0.41). Similarly, no associations were observed with intakes of total sugar (CD, P-trend = 0.50; UC, P-trend = 0.71) or starch (CD, P-trend = 0.69; UC, P-trend = 0.17). Conclusions: The lack of associations with these nutrients is in agreement with many case-control studies that have not identified associations with CD or UC. As there is biological plausibility for how specific carbohydrates could have an etiological role in inflammatory bowel disease, future epidemiological work should assess individual carbohydrates, although there does not seem to be a macronutrient effect.
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| 5. |
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| 6. |
- de Ridder, Lissy, et al.
(författare)
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Malignancy and Mortality in Pediatric Patients with Inflammatory Bowel Disease : A Multinational Study from the Porto Pediatric IBD Group
- 2014
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Ingår i: Inflammatory Bowel Diseases. - 1078-0998 .- 1536-4844. ; 20:2, s. 291-300
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Tidskriftsartikel (refereegranskat)abstract
- Background: The combination of the severity of pediatric-onset inflammatory bowel disease (IBD) phenotypes and the need for intense medical treatment may increase the risk of malignancy and mortality, but evidence regarding the extent of the problem is scarce. Therefore, the Porto Pediatric IBD working group of ESPGHAN conducted a multinational-based survey of cancer and mortality in pediatric IBD. Methods: A survey among pediatric gastroenterologists of 20 European countries and Israel on cancer and/or mortality in the pediatric patient population with IBD was undertaken. One representative from each country repeatedly contacted all pediatric gastroenterologists from each country for reporting retrospectively cancer and/or mortality of pediatric patients with IBD after IBD onset, during 2006-2011. Results: We identified 18 cases of cancers and/or 31 deaths in 44 children (26 males) who were diagnosed with IBD (ulcerative colitis, n = 21) at a median age of 10.0 years (inter quartile range, 3.0-14.0). Causes of mortality were infectious (n = 14), cancer (n = 5), uncontrolled disease activity of IBD (n = 4), procedure-related (n = 3), other non-IBD related diseases (n = 3), and unknown (n = 2). The most common malignancies were hematopoietic tumors (n = 11), of which 3 were hepatosplenic T-cell lymphoma and 3 Ebstein-Barr virus-associated lymphomas. Conclusions: Cancer and mortality in pediatric IBD are rare, but cumulative rates are not insignificant. Mortality is primarily related to infections, particularly in patients with 2 or more immunosuppressive agents, followed by cancer and uncontrolled disease. At least 6 lymphomas were likely treatment-associated by virtue of their phenotype.
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| 7. |
- Halfvarson, Jonas, 1970-
(författare)
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Genetics in twins with Crohn's disease : less pronounced than previously believed?
- 2011
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Ingår i: Inflammatory Bowel Diseases. - : John Wiley & Sons. - 1078-0998 .- 1536-4844. ; 17:1, s. 6-12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The influence of genetics in inflammatory bowel disease is emphasized by twin concordance. Previous studies have methodological limitations. The aims were to establish reliable concordance rates and compare phenotypic characteristics in concordant and discordant monozygotic pairs, anticipating the former reflects a genetically determined subgroup.METHODS: By re-running the Swedish twin registry with the Swedish hospital discharge register, observation time was extended. Diagnoses and phenotype were based on medical notes. Pairs with unknown zygosity and where both twins were not alive or not responding to the questionnaire were excluded. In all, 149 new twin pairs of the same sex, born 1909-1980 were identified.RESULTS: Of new pairs, 4/29 monozygotic, 0/38 dizygotic, and 0/1 twin pairs with unknown zygosity were concordant for Crohn's disease (CD). In ulcerative colitis (UC), 4/31 monozygotic, 4/48 dizygotic, and 0/1 twin pairs with unknown zygosity were concordant. New pairs were added to the original cohort. Restricting analyses to pairs born 1886-1958, the time period used in the original cohort, 9/33 monozygotic and 1/50 dizygotic pairs were concordant for CD (P = 0.008), 6/41 and 3/49, correspondingly, for UC (P = 0.29). There was a trend for concordant twins to have less colonic CD than discordant twins, 15% versus 35% (P = 0.09) in twins born 1886-1980.CONCLUSIONS: Previous twin studies have overestimated the influence of genetics in CD. A trend for phenotypic difference between concordant and discordant pairs was observed, suggesting that the clinical entity represents diseases with different pathophysiological backgrounds.
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| 8. |
- Holmén Larsson, Jessica, 1971, et al.
(författare)
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Altered O-glycosylation profile of MUC2 mucin occurs in active ulcerative colitis and is associated with increased inflammation.
- 2011
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Ingår i: Inflammatory bowel diseases. - : Oxford University Press (OUP). - 1536-4844 .- 1078-0998.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The MUC2 mucin organizes the two mucus layers in the colon. This mucin carries a large number of O-glycans that are assumed to be attachment sites for the commensal flora found in the outer mucus layer. METHODS: Single biopsies from the sigmoid colon of controls (25) and patients with inactive (13) or active (15) ulcerative colitis (UC) were collected during routine colonoscopy. The insoluble MUC2 mucin was prepared and separated by gel electrophoresis, its relative amount estimated, its O-glycans released, and glycans analyzed by novel sensitive glycomics chromatography / mass spectrometry providing information on glycan structures and relative abundances. The glycosylation pattern was related to the degree of mucosal inflammation and clinical severity of the disease. RESULTS: The relative abundance of MUC2 showed high individual variability. Two major glycan profiles were found; a normal pattern in the control and inactive UC patients and an aberrant profile in patients with active colitis with an increase in a subset of the smaller glycans and a decrease of several complex glycans. The magnitude of this phenomenon was significantly related to both the degree of inflammation in the biopsies and also to some extent the severity of disease course. The aberrant profile was further shown to be reversible upon remission. CONCLUSIONS: In the majority of the active UC patients MUC2 mucin has an altered glycan profile as compared to inactive UC and control patients. Patients with strong alterations in the glycan pattern tended to have a more severe disease course. (Inflamm Bowel Dis 2011).
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| 9. |
- Jansson, Andreas, et al.
(författare)
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Toward quantifying the thymic dysfunction state in mouse models of inflammatory bowel disease
- 2013
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Ingår i: Inflammatory Bowel Diseases. - Philadelphia, USA : Lippincott Williams & Wilkins. - 1078-0998 .- 1536-4844. ; 19:4, s. 881-888
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Forskningsöversikt (refereegranskat)abstract
- Inflammatory bowel disease is characterized by a number of immunological alterations, not the least in the T-cell compartment. Numerous animal models of colitis have revealed aberrant thymocyte dynamics associated with skewed thymocyte development. The recent advancements in quantitative methods have proposed critical kinetic alterations in the thymocyte development during the progression of colitis. This review focuses on the aberrant thymocyte dynamics in Gαi2-deficient mice as this mouse model provides most quantitative data of the thymocyte development associated with colitis. Herein, we discuss several dynamic changes during the progression of colitis and propose a hypothesis for the underlying causes for the skewed proportions of the thymocyte populations seen in the Gαi2-deficient mice and in other mouse models of colitis.
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| 10. |
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