Stability Of Gut Microbiota Over Time In Crohn's Disease Patients Compared To Healthy Relatives

in Journal of Crohn’s and Colitis [=JCC] (2008), 2(1), 94

Long-term outcome after infliximab for refractory ulcerative colitis

in Journal of Crohn’s and Colitis [=JCC] (2008), 2(3), 219-225

Background and aims: Infliximab (IFX) has been shown efficacious for moderate-to-severe ulcerative colitis (UC), but data on long-term efficacy are tacking. We investigated long-term outcome including ... [more ▼]

Background and aims: Infliximab (IFX) has been shown efficacious for moderate-to-severe ulcerative colitis (UC), but data on long-term efficacy are tacking. We investigated long-term outcome including colectomy rates in outpatients treated with IFX for refractory UC in a single referral centre, and evaluated if predictors could be identified. Methods: The first 121 outpatients (median age 38.0 years) with refractory UC treated with IFX were included. The primary outcome was colectomy-free survival. Secondary measures were sustained clinical response and serious adverse events. Results: From the 81 patients (67%) with an initial clinical response to IFX, 68% had a sustained clinical response. No independent predictors of sustained clinical response could be identified. Over a median (IQR) follow-up period of 33.0 (17.0-49.8) months, 21 patients (17%) came to colectomy. Independent predictors of colectomy were absence of short-term clinical response [Hazard ratio 10.8 (95% Cl 3.5-32.8), p < 0.001], a baseline CRP level >= 5 mg/L [Hazard ratio 14.5 (95% Cl 2.0-108.6), p=0.006] and previous IV treatment with corticosteroids and/or cyctosporine [Hazard ratio 2.4 (95% Cl 1.1-5.9), p=0.033]. Six patients developed a serious infection, three a malignancy, two a post-operative complication and one patient died (suicide). Conclusions: With a median follow-upof 33.0 months after start of IFX, 17% of patients with refractory UC needed colectomy, while sustained clinical response was present in 68% of initial responders. (c) 2008 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved. [less ▲]

Mucosal gene signatures to predict response to infliximab in patients with inflammatory bowel disease

in Journal of Crohn’s and Colitis [=JCC] (2008), 2(1), 64

Genetic markers and the risk of complicated disease behaviour in Crohn's disease patients

in Gastroenterology (2008), 134(4), 349-349

Effect of infliximab treatment on colonic mucosal gene expression profiles in patients with inflammatory bowel disease

in Gut (2008), 57(Suppl II), 39

Microarray study of mucosal antimicrobial peptides in patients with inflammatory bowel disease before and after first infliximab treatment

in Gastroenterology (2008), 134

An insertion-deletion polymorphism in the Interferon Regulatory Factor 5 (IRF5) gene confers risk of inflammatory bowel diseases

in Human Molecular Genetics (2007), 16(24), 3008-3016

The interferon regulatory factor 5 (IRF5) gene encodes a transcription factor that plays an important role in the innate as well as in the cell-mediated immune responses. The IRF5 gene has been shown to ... [more ▼]

The interferon regulatory factor 5 (IRF5) gene encodes a transcription factor that plays an important role in the innate as well as in the cell-mediated immune responses. The IRF5 gene has been shown to be associated with systemic lupus erythematosus and rheumatoid arthritis. We studied whether the IRF5 gene is also associated with inflammatory bowel diseases (IBD), Crohn disease (CD) and ulcerative colitis (UC). Twelve polymorphisms in the IRF5 gene were genotyped in a cohort of 1007 IBD patients (748 CD and 254 UC) and 241 controls from Wallonia, Belgium. The same polymorphisms were genotyped in a confirmatory cohort of 311 controls and 687 IBD patients (488 CD and 192 UC) from Leuven, Belgium. A strong signal of association [P=1.9x10(-5), odds ratio (OR) 1.81 (1.37-2.39)] with IBD was observed for a 5 bp indel (CGGGG) polymorphism in the promoter region of the IRF5 gene. The association was detectable also in CD patients (P=6.8x10(-4)) and was particularly strong among the UC patients [P=5.3x10(-8), OR=2.42 (1.76-3.34)]. The association of the CGGGG indel was confirmed in the second cohort [P=3.2x10(-5), OR=1.59 (1.28-1.98)]. The insertion of one CGGGG unit is predicted to create an additional binding site for the transcription factor SP1. Using an electrophoretic mobility shift assay, we show allele-specific differences in protein binding to this repetitive DNA-stretch, which suggest a potential function role for the CGGGG indel. [less ▲]

Genetic markers and the risk of complicated disease behaviour in Crohn’s disease patients

in Gut (2007)

New serological markers in inflammatory bowel disease are associated with complicated disease behavior

in Gut (2007), 56(10), 1394-1403

OBJECTIVE: The human androgen receptor (AR) contains a polyglutamine and a polyglycine stretch which are highly polymorphic and are coded respectively by a CAG and GGN repeat in exon 1 of the AR gene ... [more ▼]

OBJECTIVE: The human androgen receptor (AR) contains a polyglutamine and a polyglycine stretch which are highly polymorphic and are coded respectively by a CAG and GGN repeat in exon 1 of the AR gene. Although the in vitro studies indicated a possible effect of the GGN repeat polymorphism on the AR gene transcription and clinical observations suggest that it might modulate the androgen action, its functional significance remains unclear. We wanted to assess whether the GGN repeat affects the serum testosterone levels in healthy men, which is the expected outcome through feedback regulation if it influences androgen action as has been shown to be the case for the CAG repeat. DESIGN AND PATIENTS: A population based cross-sectional cohort study including 1476 healthy young, middle-aged, and elderly men. MEASUREMENT: Testosterone and LH levels were determined by immunoassay; free testosterone (FT) levels were calculated. Genotyping of the GGN repeat was performed using the sequencing technique. RESULTS: The GGN repeat number was significantly associated with circulating testosterone and FT levels (P=0.017 and P=0.013 respectively). However, taking into account that age, body mass index, and CAG are already in the regression model, the GGN repeat could explain only a small part of the variation of both testosterone and FT. CONCLUSION: To our knowledge, this study is the first to demonstrate a significant positive association between the GGN repeat and androgen levels in a large cohort of healthy men. Although the present study thus adds credence to the view that the polyglycine tract in the AR can modulate AR action, this effect appears to be only small so that its clinical relevance remains questionable. [less ▲]

Genetic markers and the risk of complicated disease behaviour in Crohn's disease patients

in Gastroenterology (2007), 132(4), 17-18