| 1. |
- Almer, Sven, 1953-, et al.
(författare)
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Leukocyte scintigraphy compared to intraoperative small bowel enteroscopy and laparotomy findings in Crohn's disease
- 2007
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Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1078-0998 .- 1536-4844. ; 13:2, s. 164-174
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Tidskriftsartikel (refereegranskat)abstract
- Background: Leukocyte scintigraphy is a noninvasive investigation to assess inflammation. We evaluated the utility of labeled leukocytes to detect small bowel inflammation and disease complications in Crohn's disease and compared it to whole small bowel enteroscopy and laparotomy findings.Methods: Scintigraphy with technetium-99m exametazime-labeled leukocytes was prospectively performed in 48 patients with Crohn's disease a few days before laparotomy; 41 also had an intraoperative small bowel enteroscopy. The same procedures were performed in 8 control patients. Independent grading of scans was compared with the results of enteroscopy and with surgical, histopathologic, and clinical data.Results: In the 8 control patients leukocyte scan, endoscopy, and histopathology were all negative for the small bowel. In patients with Crohn's disease and small bowel inflammation seen at enteroscopy and/or laparotomy (n = 39) the scan was positive in 33. In 8 patients without macroscopic small bowel inflammation, the scan was positive for the small bowel in 3 patients; at histology, 2 of 3 had inflammation. When combining results for patients and controls, the sensitivity of leukocyte scan for macroscopically evident small bowel inflammation was 0.85, specificity 0.81, accuracy 0.84, positive predictive value 0.92, and negative predictive value 0.68. Scintigraphy detected inflammatory lesions not known before laparotomy in 16 of 47 (34%) Crohn's disease patients and showed uptake in 25 of 35 (71%) bowel strictures. It was diagnostic regarding 4 of 8 abscesses and 9 of 15 fistulas. In 6 patients (13%) lesions first demonstrated by leukocyte scintigraphy were treated during the surgery performed.Conclusions: Leukocyte scintigraphy reliably detects small bowel inflammation in Crohn's disease. It gives additional information on the presence of inflammatory lesions in a fraction of patients planned for surgery.
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| 2. |
- Franke, Andre, et al.
(författare)
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Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1118-1125
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Tidskriftsartikel (refereegranskat)abstract
- We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
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| 3. |
- Momozawa, Yukihide, et al.
(författare)
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Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease
- 2011
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Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 43:1, s. 43-47
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified dozens of risk loci for many complex disorders, including Crohn's disease. However, common disease-associated SNPs explain at most ∼20% of the genetic variance for Crohn's disease. Several factors may account for this unexplained heritability, including rare risk variants not adequately tagged thus far in GWAS. That rare susceptibility variants indeed contribute to variation in multifactorial phenotypes has been demonstrated for colorectal cancer, plasma high-density lipoprotein cholesterol levels, blood pressure, type 1 diabetes, hypertriglyceridemia and, in the case of Crohn's disease, for NOD2 (refs. 14,15). Here we describe the use of high-throughput resequencing of DNA pools to search for rare coding variants influencing susceptibility to Crohn's disease in 63 GWAS-identified positional candidate genes. We identify low frequency coding variants conferring protection against inflammatory bowel disease in IL23R, but we conclude that rare coding variants in positional candidates do not make a large contribution to inherited predisposition to Crohn's disease.
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| 4. |
- Soderman, Jan, et al.
(författare)
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Analysis of single nucleotide polymorphisms in the region of CLDN2-MORC4 in relation to inflammatory bowel disease
- 2013
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 19:30, s. 4935-4943
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To investigate a possible genetic influence of claudin (CLDN) 1, CLDN2 and CLDN4 in the etiology of inflammatory bowel disease.METHODS: Allelic association between genetic regions of CLDN1, CLDN2 or CLDN4 and patients with inflammatory bowel disease, Crohn's disease (CD) or ulcerative colitis were investigated using both a case-control study approach (one case randomly selected from each of 191 Swedish inflammatory bowel disease families and 333 controls) and a family-based study (463 non-Swedish European inflammatory bowel disease-families). A nonsynonymous coding single nucleotide polymorphism in MORC4, located on the same linkage block as CLDN2, was investigated for association, as were two novel CLDN2 single nucleotide polymorphism markers, identified by resequencing.RESULTS: A single nucleotide polymorphism marker (rs12014762) located in the genetic region of CLDN2 was significantly associated to CD (case-control allelic OR = 1.98, 95% CI: 1.17-3.35, P = 0.007). MORC4 was present on the same linkage block as this CD marker. Using the case-control approach, a significant association (case control allelic OR = 1.61, 95% CI: 1.08-2.41, P = 0.018) was found between CD and a nonsynonymous coding single nucleotide polymorphism (rs6622126) in MORC4. The association between the CLDN2 marker and CD was not replicated in the family-based study. Ulcerative colitis was not associated to any of the single nucleotide polymorphism markers.CONCLUSION: These findings suggest that a variant of the CLDN2-MORC4 region predisposes to CD in a Swedish population.
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| 5. |
- van Asseldonk, Dirk P, et al.
(författare)
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Difficulties and possibilities with thiopurine therapy in inflammatory bowel disease-Proceedings of the first Thiopurine Task Force meeting
- 2011
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Ingår i: DIGESTIVE AND LIVER DISEASE. - : Elsevier Science B.V., Amsterdam. - 1590-8658. ; 43:4, s. 270-276
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Tidskriftsartikel (refereegranskat)abstract
- Background: Thiopurines, such as azathioprine and mercaptopurine, are of pivotal importance in the treatment of inflammatory bowel disease. Although these drugs have been used for several decades, still many questions remain unanswered. Aim: To provide an overview of clinically and scientifically challenging topics concerning thiopurine therapy in inflammatory bowel disease treatment. Methods: The first meeting of the Thiopurine Task Force Interest Group was held during the 2009 United European Gastroenterology Week in London (GASTRO2009). The topics of this meeting were of particular clinical and scientific interest. Additional literature was identified by performing a Pubmed search using the search terms inflammatory bowel disease, azathioprine, 6-mercaptopurine and thioguanine. Results: The following topics were discussed: therapeutic drug monitoring; the synergy of thiopurines with aminosalicylates and allopurinol; serious adverse events such as opportunistic infections, hepatotoxicity, carcinogenicity and pancreatitis; prolongation of thiopurines during clinical remission; indications for thiopurines in the postoperative setting; and the potential use of thioguanine. Specific interesting and clinically relevant topics for potential future research are provided. Conclusions: Thiopurines remain central to inflammatory bowel disease treatment, although future studies are required to substantiate a more personalised medicine approach to their use.
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