Clinical predictors of inflammatory bowel disease in a genetically well-defined Caucasian population

Kanaan, Ziad; Eichenberger, M. Robert; Ahmad, Surriya; Weller, Clayton; Roberts, Henry L.; Pan, Jianmin; Shesh, N.; Petras, Robert E.; Weller, E. Brooks; Galandiuk, Susan

doi:10.1186/1477-5751-11-7

Cited by 11 publications

(6 citation statements)

References 33 publications

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“…Therefore, this defective innate response to C. jejuni infection is insufficient to promote colitis, and a more global immune alteration, such as the one afforded by absence of IL-10 signaling in Il10 −/− mice is necessary to reveal NOD2 contribution. This two hit model is compatible with the limited risk factor confer by NOD2 polymorphisms in humans, which highlights the polygenic nature of IBD [38,39].…”

Section: Discussionsupporting

confidence: 66%

Nucleotide-Binding Oligomerization Domain–Containing Protein 2 Controls Host Response to Campylobacter jejuni in Il10−/− Mice

Sun¹,

Jobin

2014

The Journal of Infectious Diseases

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Innate signaling-induced antimicrobial response represents a key protective host feature against infectious microorganisms such as Campylobacter species. In this study, we investigated the role of nucleotide-binding oligomerization domain-containing protein 2 (NOD2) in Campylobacter jejuni-induced intestinal inflammation. Specific-pathogen-free Il10(-/-), Nod2(-/-), and Il10(-/-); Nod2(-/-) mice were infected with C. jejuni (10(9) colony-forming units/mouse) 24 hours after a 7-day course of antibiotic treatment. Three weeks later, host responses were determined. The nitric oxide (NO) donor sodium nitroprusside was injected intraperitoneally (2 mg/kg daily) to supplement NO. Although healthy in specific-pathogen-free conditions, Il10(-/-); Nod2(-/-) mice developed severe intestinal inflammation following C. jejuni infection, compared with Nod2(-/-) and Il10(-/-) mice. The onset of colitis was associated with elevated neutrophil accumulation, crypt abscesses, and expression of the endogenous proinflammatory mediators Il-1β, Tnfα, and Cxcl1. Fluorescence in situ hybridization and culture assay showed enhanced C. jejuni invasion into the colon and mesenteric lymph nodes in Il10(-/-); Nod2(-/-) mice, compared with Il10(-/-) mice. C. jejuni-induced bactericidal NO production was reduced in peritoneal macrophages from Il10(-/-); Nod2(-/-) mice, compared with Il10(-/-) mice. Importantly, sodium nitroprusside attenuated C. jejuni-induced colitis in Il10(-/-); Nod2(-/-) mice. Our findings suggest that NOD2 signaling is critical to control campylobacteriosis in Il10(-/-) mice, a process involving NOD2-mediated bactericidal responses.

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Section: Discussionsupporting

confidence: 66%

Nucleotide-Binding Oligomerization Domain–Containing Protein 2 Controls Host Response to Campylobacter jejuni in Il10−/− Mice

Sun¹,

Jobin

2014

The Journal of Infectious Diseases

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“…All samples were genotyped for 14 single nucleotide polymorphisms (SNPs) associated with IBD and risk allele frequencies (RAFs) were calculated. For all SNPs, the RAFs observed in our population were comparable to those in other large IBD populations [ 8 , 26 ] as shown in Table 2 . Individual SNP frequencies for IBD overall, and for CD and UC, are provided in Multimedia Appendix 1 .…”

Section: Resultssupporting

confidence: 86%

Collecting Biospecimens From an Internet-Based Prospective Cohort Study of Inflammatory Bowel Disease (CCFA Partners): A Feasibility Study

Randell

As²,

Cook³

et al. 2016

JMIR Res Protoc

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BackgroundThe Internet has successfully been used for patient-oriented survey research. Internet-based translational research may also be possible.ObjectiveOur aim was to study the feasibility of collecting biospecimens from CCFA Partners, an Internet-based inflammatory bowel disease (IBD) cohort.MethodsFrom August 20, 2013, to January 4, 2014, we randomly sampled 412 participants, plus 179 from a prior validation study, and invited them to contribute a biospecimen. Participants were randomized to type (blood, saliva), incentive (none, US $20, or US $50), and collection method for blood. The first 82 contributors were also invited to contribute stool. We used descriptive statistics and t tests for comparisons.ResultsOf the 591 participants, 239 (40.4%) indicated interest and 171 (28.9%) contributed a biospecimen. Validation study participants were more likely to contribute than randomly selected participants (44% versus 23%, P<.001). The return rate for saliva was higher than blood collected by mobile phlebotomist and at doctors’ offices (38%, 31%, and 17% respectively, P<.001). For saliva, incentives were associated with higher return rates (43-44% versus 26%, P=.04); 61% contributed stool. Fourteen IBD-associated single nucleotide polymorphisms were genotyped, and risk allele frequencies were comparable to other large IBD populations. Bacterial DNA was successfully extracted from stool samples and was of sufficient quality to permit quantitative polymerase chain reaction for total bacteria.ConclusionsParticipants are willing to contribute and it is feasible to collect biospecimens from an Internet-based IBD cohort. Home saliva kits yielded the highest return rate, though mobile phlebotomy was also effective. All samples were sufficient for genetic testing. These data support the feasibility of developing a centralized collection of biospecimens from this cohort to facilitate IBD translational studies.

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“…There are many logistic models that show the relationship between IBD varieties [26][27][28][29][30][31]. However, the most accurate model which could clearly point the appropriate group for the patient has not been found so far.…”

Section: Discussionmentioning

confidence: 99%

Smart Model to Distinguish Crohn’s Disease from Ulcerative Colitis

2019

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Inflammatory bowel diseases (IBD) is a term referring to chronic and recurrent gastrointestinal disease. It includes Crohn’s disease (CD) and ulcerative colitis (UC). It is undeniable that presenting features may be unclear and do not enable differentiation between disease types. Therefore, additional information, obtained during the analysis, can definitely provide a potential way to differentiate between UC and CD. For that reason, finding the optimal logistic model for further analysis of collected medical data, is a main factor determining the further precisely defined decision class for each examined patient. In our study, 152 patients with CD or UC were included. The collected data concerned not only biochemical parameters of blood but also very subjective information, such as data from interviews. The built-in logistics model with very high precision was able to assign patients to the appropriate group (sensitivity = 0.84, specificity = 0.74, AUC = 0.93). This model indicates factors differentiating between CD and UC and indicated odds ratios calculated for significantly different variables in these two groups. All obtained parameters of the model were checked for statistically significant. The constructed model was able to be distinguish between ulcerative colitis and Crohn’s disease.

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Clinical predictors of inflammatory bowel disease in a genetically well-defined Caucasian population

Cited by 11 publications

References 33 publications

Nucleotide-Binding Oligomerization Domain–Containing Protein 2 Controls Host Response to Campylobacter jejuni in Il10−/− Mice

Nucleotide-Binding Oligomerization Domain–Containing Protein 2 Controls Host Response to Campylobacter jejuni in Il10−/− Mice

Collecting Biospecimens From an Internet-Based Prospective Cohort Study of Inflammatory Bowel Disease (CCFA Partners): A Feasibility Study

Smart Model to Distinguish Crohn’s Disease from Ulcerative Colitis

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