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- Zhulina, Yaroslava, 1973-, et al.
(författare)
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Subclinical Inflammation with Increased Neutrophil Activity in Healthy Twin Siblings Reflect Environmental Influence in the Pathogenesis of Inflammatory Bowel Disease
- 2013
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Ingår i: Inflammatory Bowel Diseases. - Philadelphia, USA : Lippincott Williams & Wilkins. - 1078-0998 .- 1536-4844. ; 19:8, s. 1725-1731
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Tidskriftsartikel (refereegranskat)abstract
- Background: The mechanisms behind increased fecal calprotectin (FC) in healthy relatives of patients with inflammatory bowel disease (IBD) are unknown. Our aims were to explore if there is a subclinical inflammation with increased neutrophil activity in healthy twin siblings in discordant twin pairs with IBD and to assess the influence of genetics in this context.Methods: Nuclear factor kappa B (NF-B) and neutrophil activity, based on myeloperoxidase (MPO) and FC, were analyzed in healthy twin siblings in discordant twin pairs with IBD and compared with healthy controls. NF-B and MPO were assessed by immunohistochemistry and FC by enzyme-linked immunosorbent assay.Results: In total, 33 of 34 healthy twin siblings were histologically normal. Increased NF-B was more often observed in healthy twin siblings in discordant twin pairs with Crohn's disease (13/18 [73%]) and with ulcerative colitis (12/16 [75%]) than in healthy controls (8/45 [18%]). MPO was more often increased in healthy twin siblings in discordant pairs with Crohn's disease (12/18 [67%]) than in healthy controls (11/45 [24%]) and FC more often in healthy twin siblings in discordant pairs with ulcerative colitis (14/21 [67%]) than in healthy controls (6/31 [19%]). Interestingly, the observed differences remained when healthy monozygotic and dizygotic twin siblings were analyzed separately.Conclusions:We observed increased NF-B, MPO, and FC in healthy twins in both monozygotic and dizygotic discordant pairs with IBD. These novel findings speak for an ongoing subclinical inflammation with increased neutrophil activity in healthy first-degree relatives.
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| 2. |
- Erickson, Alison R, et al.
(författare)
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Integrated metagenomics/metaproteomics reveals human host-microbiota signatures of Crohn's disease
- 2012
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Ingår i: PLOS ONE. - San Francisco : Public Library Science. - 1932-6203. ; 7:11
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Tidskriftsartikel (refereegranskat)abstract
- Crohn's disease (CD) is an inflammatory bowel disease of complex etiology, although dysbiosis of the gut microbiota has been implicated in chronic immune-mediated inflammation associated with CD. Here we combined shotgun metagenomic and metaproteomic approaches to identify potential functional signatures of CD in stool samples from six twin pairs that were either healthy, or that had CD in the ileum (ICD) or colon (CCD). Integration of these omics approaches revealed several genes, proteins, and pathways that primarily differentiated ICD from healthy subjects, including depletion of many proteins in ICD. In addition, the ICD phenotype was associated with alterations in bacterial carbohydrate metabolism, bacterial-host interactions, as well as human host-secreted enzymes. This eco-systems biology approach underscores the link between the gut microbiota and functional alterations in the pathophysiology of Crohn's disease and aids in identification of novel diagnostic targets and disease specific biomarkers.
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| 3. |
- Fransén, Karin, 1973-, et al.
(författare)
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Polymorphism in the retinoic acid metabolizing enzyme CYP26B1 and the development of Crohn's disease
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8, s. e72739-
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Tidskriftsartikel (refereegranskat)abstract
- Several studies suggest that Vitamin A may be involved in the pathogenesis of inflammatory bowel disease (IBD), but the mechanism is still unknown. Cytochrome P450 26 B1 (CYP26B1) is involved in the degradation of retinoic acid and the polymorphism rs2241057 has an elevated catabolic function of retinoic acid, why we hypothesized that the rs2241057 polymorphism may affect the risk of Crohn's disease (CD) and Ulcerative Colitis (UC). DNA from 1378 IBD patients, divided into 871 patients with CD and 507 with UC, and 1205 healthy controls collected at Örebro University Hospital and Karolinska University Hospital were analyzed for the CYP26B1 rs2241057 polymorphism with TaqMan® SNP Genotyping Assay followed by allelic discrimination analysis. A higher frequency of patients homozygous for the major (T) allele was associated with CD but not UC compared to the frequency found in healthy controls. A significant association between the major allele and non-stricturing, non-penetrating phenotype was evident for CD. However, the observed associations reached borderline significance only, after correcting for multiple testing. We suggest that homozygous carriers of the major (T) allele, relative to homozygous carriers of the minor (C) allele, of the CYP26B1 polymorphism rs2241057 may have an increased risk for the development of CD, which possibly may be due to elevated levels of retinoic acid. Our data may support the role of Vitamin A in the pathophysiology of CD, but the exact mechanisms remain to be elucidated.
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| 4. |
- Gustavsson, Anders, 1964-, et al.
(författare)
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Endoscopic dilation is an efficacious and safe treatment of intestinal strictures in Crohn's disease
- 2012
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Ingår i: Alimentary Pharmacology and Therapeutics. - Hoboken, USA : Wiley-Blackwell. - 0269-2813 .- 1365-2036. ; 36:2, s. 151-158
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Tidskriftsartikel (refereegranskat)abstract
- Background: Bowel strictures are a major cause of morbidity, hospitalisation and surgery in Crohn's disease.Aim: We report short- and long-term efficacy and safety of endoscopic balloon dilation of strictures due to Crohn's disease.Methods: Retrospective study of patients who underwent endoscopic balloon dilation between 1987 and 2009.Results: We performed 776 dilations, of which 621 (80%) were on anastomotic strictures, in 178 patients (94 women) with Crohn's disease. At first dilation, median (IQR) age of patients was 45 (37-56) years and disease duration 16 (8-22) years. Technical success rate was 689/776 (89%). A subset of 75 patients from the primary catchment area, with >5-year follow-up, underwent a total of 246 dilations. At 1-year follow-up, 60/75 (80%) patients had undergone no further intervention or one additional dilation only. At 3 and 5 years, corresponding figures were 43/75 (57%) and 39/75 (52%). Cumulative proportions of patients undergoing surgery at 1, 3 and 5 years were 13%, 28% and 36%. Complication rate per procedure for all 178 patients was 41/776 (5.3%), bowel perforation (n = 11, 1.4%), major bleeding requiring blood transfusion (n = 8, 1.0%), minor bleeding (n = 10, 1.3%) and abdominal pain or fever (n = 12, 1.5%). Ten patients underwent surgery due to complications (perforation n = 8, bleeding n = 2). There was no procedure-related mortality.Conclusion: Endoscopic balloon dilation is an efficacious and safe alternative to surgical resection of intestinal strictures in Crohn's disease. At 5-year follow-up, 52% of patients required no further or one additional dilation only, whereas 36% had undergone surgical resection. Complication frequency was low.
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| 6. |
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| 7. |
- Gustavsson, Anders, 1964-, et al.
(författare)
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Smoking is a risk factor for recurrence of intestinal stricture after endoscopic dilation in Crohn's disease
- 2013
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley-Blackwell. - 0269-2813 .- 1365-2036. ; 37:4, s. 430-437
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Endoscopic balloon dilation is an efficacious and safe alternative to surgery as treatment of short intestinal strictures in Crohn's disease (CD). Factors predicting outcome of the procedure are not well described.AIM: To evaluate whether smoking at diagnosis, treatment with azathioprine, or other clinical variables may affect clinical outcome after endoscopic dilation. The endpoint was requirement of a new intervention such as dilation or surgery with intestinal resection or strictureplasty.METHODS: Retrospective study of 83 patients with CD who underwent endoscopic balloon dilation of an intestinal stricture between 1987 and 2009.RESULTS: After index dilation 55/83 patients underwent a new intervention. Among current smokers, 31/32 (97%) underwent another intervention compared to 18/33 (55%) among never smokers (adjusted HR: 2.50, 95% CI: 1.14-5.50, P = 0.022). After 5 years, cumulative probability of new intervention was 0.81 in smokers compared to 0.52 in never smokers; difference 0.29 (95% CI: 0.07-0.52, P = 0.01). In 16 patients, therapy with azathioprine was initiated before or shortly after the index dilation; 7/16 underwent a new intervention compared to 48/67 of those without azathioprine (HR: 0.46, 95% CI: 0.21-1.03, P = 0.06). After adjustment for other variables, the association was even weaker (HR: 0.80, 95% CI: 0.29-2.18, P = 0.668). Sex, age at diagnosis, age at first dilation, balloon size, location of stricture, and treatment period did not influence outcome.CONCLUSIONS: Smoking doubles the risk of recurrent stricture formation requiring a new intervention after index dilation. Maintenance therapy with azathioprine did not influence the subsequent course and need for a new intervention.
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| 8. |
- Halfvarson, Jonas, 1970-, et al.
(författare)
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Inflammatory bowel disease in a Swedish twin cohort : a long-term follow-up of concordance and clinical characteristics
- 2003
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Ingår i: Gastroenterology. - 0016-5085 .- 1528-0012. ; 124:7, s. 1767-1773
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims:In 1988, we reported the first twin study in inflammatory bowel disease. The aim of the current study was to follow up these twins regarding new cases of inflammatory bowel disease and Crohn’s disease characteristics using the Vienna classification.Methods:The official Swedish population register and the cause of death register were used to search for the twins. All living patients were interviewed.Results:Three monozygotic twins earlier classified as healthy had been diagnosed with inflammatory bowel disease (ulcerative colitis, n = 2; Crohn’s disease, n = 1). Retrospectively, all 3 were symptomatic at the original survey. This changed the pair concordance in monozygotic twins from 6.3% to 18.8% in ulcerative colitis and from 44.4% to 50.0% in Crohn’s disease. A high degree of concordance regarding age at diagnosis, disease location at diagnosis and during the course, and disease behavior was found in concordant monozygotic twin pairs with Crohn’s disease. Seven of 9 pairs were identical in 3 or more of these disease characteristics compared with an expected number of 1.5 (P = 0.000076).Conclusions:This study confirms that the genetic influence is stronger in Crohn’s disease than in ulcerative colitis. A remarkable phenotype similarity within concordant pairs with Crohn’s disease was found using the Vienna classification.
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| 9. |
- Halfvarson, Jonas, 1970-, et al.
(författare)
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Longitudinal concordance for clinical characteristics in a Swedish-Danish twin population with inflammatory bowel disease
- 2007
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Ingår i: Inflammatory Bowel Diseases. - New York, NY : Raven Press. - 1078-0998 .- 1536-4844. ; 13:12, s. 1536-1544
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The genetic influence on disease course in inflammatory bowel disease (IBD) remains unknown. We therefore aimed to study longitudinal concordance for clinical characteristics and longitudinal stability using the Montreal Classification in an IBD twin population. METHODS: A total of 158 twins with ulcerative colitis (UC) (18 belonging to 9 concordant monozygotic pairs) and 141 twins with Crohn's disease (CD) (34 belonging to 17 concordant monozygotic pairs) were enrolled. Medical notes were scrutinized for clinical characteristics at diagnosis and after 10 years. Using the binominal distribution, we tested the hypothesis that clinical characteristics were independent within individuals in disease concordant monozygotic pairs. RESULTS: In CD, location was identical in 11/17 monozygotic concordant pairs at diagnosis (P = 0.008) and in 11/16 pairs after 10 years (P = 0.02). Behavior at diagnosis was identical in 13/17 pairs (P = 0.03) and in 11/16 pairs after 10 years (P = 0.01). Monozygotic UC twins were concordant (within 5 years) for age at diagnosis (6/9 pairs; P < 0.001) and symptomatic onset (4/9 pairs; P = 0.02) but not for extent of disease at diagnosis or after 10 years. The Montreal Classification did not demonstrate longitudinal stability, either regarding location or behavior of CD or extent of UC. CONCLUSIONS: The high phenotypic concordance, both at diagnosis and longitudinally, in monozygotic twins with CD supports a genetic influence not only on disease occurrence but also on disease course. This contrasts with UC, where the genetic impact appears less. Montreal Classification characteristics changed over time and should be used cautiously.
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