Profile of Belgian Pediatric Crohn's Disease Patients: Presentation and diagnostic features

in Gastroenterology (2011), 140(5), 786

Profile of Belgian Pediatric Crohn's Disease Patients: Presentation and diagnostic features

in Journal of Crohn’s and Colitis [=JCC] (2011), 5(1), 155

Effects of haptoglobin polymorphisms and deficiency on susceptibility to inflammatory bowel disease and on severity of murine colitis.

in Gut (2011), 61(4), 528-534

BackgroundHaptoglobin (Hp) is a haemoglobin-binding protein with immunomodulatory properties. Its gene (16q22) harbours a common polymorphism with two different alleles: Hp1 and Hp2. Genotype Hp22 has ... [more ▼]

BackgroundHaptoglobin (Hp) is a haemoglobin-binding protein with immunomodulatory properties. Its gene (16q22) harbours a common polymorphism with two different alleles: Hp1 and Hp2. Genotype Hp22 has been shown to be over-represented in different immune diseases. Results in Crohn's disease (CD) are contradictory.AimsTo determine whether Hp plays a role in inflammatory bowel disease, both genetically and functionally.Methods1061 patients with CD, 755 with ulcerative colitis (UC) and 152 with primary sclerosing cholangitis, as well as 452 healthy controls, were genotyped using touch-down PCR. To confirm association results, 464 CD trios and 151 UC trios were genotyped. Serum Hp concentrations were determined in 62 individuals of different genotype. Colitis was induced in mice with dextran sulphate sodium (DSS) and oxazolone (Oxa). Cytokine production was evaluated by mRNA quantification in colonic tissue and ELISA on supernatants of mesenteric lymph node cells.ResultsPrevalence of Hp2 was higher in CD and UC than in controls. In the confirmatory cohorts, Hp2 was over-transmitted to the affected offspring. Serum Hp concentrations were higher in individuals with genotypes Hp11 and Hp21 than in those with Hp22 (1.38 vs 0.89 g/l). DSS- and Oxa-induced colitis were more severe in Hp-deficient mice than in control mice and accompanied by higher concentrations (although not statistically significantly different) of tissue mRNA for cytokines. Interleukin-17 production was significantly higher in the presence of Hp-deficient serum compared with wild-type serum.ConclusionsThe Hp gene may play a role in susceptibility to inflammatory bowel disease. Its implication in other immune diseases underscores the common pathways between these diseases. Experimental models of colitis showed that Hp has a protective role in inflammatory colitis, most likely by inhibiting the production of Th1 and Th17 cytokines. [less ▲]

Molecular Reclassification of Crohn’s Disease by cluster analysis of genetic variants.

in Acta Gastro-Enterologica Belgica (2010)

Kinetics of C-Reactive Protein (CRP) following maintenance infliximab treatment in Crohn's disease identifies profiles of patients with better outcome

in Gastroenterology (2010), 138(5 (Suppl I)), -686

Intestinal mucosal expression of matrix metalloproteinase and ADAM genes in patients with inflammatory bowel disease and the impact of infliximab therapy

in Gastroenterology (2010), 138(5), 677

Familial Aggregation and Antimicrobial Response Dose-Dependently Affect the Risk for Crohn's Disease

in Inflammatory Bowel Diseases (2010), 16(1), 58-67

Background: An increased risk of Crohn's disease (CD) has been reported consistently in first-degree relatives of patients. Our aim was to test whether a combination of CD-associated genes involved in ... [more ▼]

Background: An increased risk of Crohn's disease (CD) has been reported consistently in first-degree relatives of patients. Our aim was to test whether a combination of CD-associated genes involved in innate immunity and/or antibody responses to microbial antigens may be valuable in identifying healthy relatives at risk. Methods: We investigated 86 families from Beloium and northern France, 45 with at least 3 first-degree relatives with CD, 24 with a single case, and 17 control families without inflammatory bowel disease (IBD). The cohort consisted of 186 CD patients, 290 healthy relatives, and 142 controls (total 618). Genetic (NOD2, NODI, TLR4, CARD8) and serologic markers (ASCA, ACMA, ALCA, ACCA, A Sigma MA, OmpC, CBir1, I2) were determined in all subjects. All Belgian families were prospectively followed up for 54 months. Results: In multiple-affected families, an increment of affected first-degree relatives and of positive antibodies were additive risks factors for CD (P < 0.0001), independent of NOD2 mutations. When comparing subjects from multiple-affected families, having 3 additional first-degree relatives with CD and 1 additional positive antibody increased the odds for CD to 9.19 (95% confidence interval [CI]: 4.07-20.80). After a follow-up of 54 months among all Belgian families, a total of 4 new diagnoses of IBD were confirmed in the multiple-affected families only, resulting in a 57-fold increase in incidence within multiple-affected families compared to the known incidence of IBD in our region. Conclusions: We found an additive risk increment for CD in subjects from multicase families per additional affected relative and per additional positive antibody, independent of NOD2. Furthermore, a very high disease incidence was observed in these multiple-affected families. [less ▲]

Molecular Reclassification of Crohn’s Disease by cluster analysis of genetic variants.

in Gastroenterology (2010), -

Cluster analysis of genetic variants enables reclassification of Crohn’s disease at the molecular level

in Gut (2009)

Predictive Value of C-Reactive Protein Level Changes On the Long Term Outcome of Infliximab in Crohn's Disease

in Gastroenterology (2009), 136(5), 171