The Role of PET/CT in the Monitoring and Diagnosis of Pediatric Inflammatory Bowel Disease.
Hustinx, Roland ; Louis, Edouard
in PET Clinics (2009), 3Detailed reference viewed: 14 (1 ULg)
Common variants in the NLRP3 region contribute to Crohn's disease susceptibility.
; ; et al
in Nature Genetics (2009), 41(1), 71-6
We used a candidate gene approach to identify a set of SNPs, located in a predicted regulatory region on chromosome 1q44 downstream of NLRP3 (previously known as CIAS1 and NALP3) that are associated with ... [more ▼]
We used a candidate gene approach to identify a set of SNPs, located in a predicted regulatory region on chromosome 1q44 downstream of NLRP3 (previously known as CIAS1 and NALP3) that are associated with Crohn's disease. The associations were consistently replicated in four sample sets from individuals of European descent. In the combined analysis of all samples (710 father-mother-child trios, 239 cases and 107 controls), these SNPs were strongly associated with risk of Crohn's disease (P(combined) = 3.49 x 10(-9), odds ratio = 1.78, confidence interval = 1.47-2.16 for rs10733113), reaching a level consistent with the stringent significance thresholds imposed by whole-genome association studies. In addition, we observed significant associations between SNPs in the associated regions and NLRP3 expression and IL-1beta production. Mutations in NLRP3 are known to be responsible for three rare autoinflammatory disorders. These results suggest that the NLRP3 region is also implicated in the susceptibility of more common inflammatory diseases such as Crohn's disease. [less ▲]Detailed reference viewed: 86 (16 ULg)
Genetic variation in the familial Mediterranean fever gene (MEFV) and risk for Crohn's disease and ulcerative colitis.
; ; Louis, Edouard et al
in PLoS ONE (2009), 4(9), 7154
BACKGROUND AND AIMS: The familial Mediterranean fever (FMF) gene (MEFV) encodes pyrin, a major regulator of the inflammasome platform controlling caspase-1 activation and IL-1beta processing. Pyrin has ... [more ▼]
BACKGROUND AND AIMS: The familial Mediterranean fever (FMF) gene (MEFV) encodes pyrin, a major regulator of the inflammasome platform controlling caspase-1 activation and IL-1beta processing. Pyrin has been shown to interact with the gene product of NLRP3, NALP3/cryopyrin, also an important active member of the inflammasome. The NLRP3 region was recently reported to be associated with Crohn's disease (CD) susceptibility. We therefore sought to evaluate MEFV as an inflammatory bowel disease (IBD) susceptibility gene. METHODOLOGY AND RESULTS: MEFV colonic mucosal gene expression was significantly increased in experimental colitis mice models (TNBS p<0.0003; DSS p<0.006), in biopsies from CD (p<0.02) and severe ulcerative colitis (UC) patients (p<0.008). Comprehensive genetic screening of the MEFV region in the Belgian exploratory sample set (440 CD trios, 137 UC trios, 239 CD cases, 96 UC cases, and 107 healthy controls) identified SNPs located in the MEFV 5' haplotype block that were significantly associated with UC (rs224217; p = 0.003; A allele frequency: 56% cases, 45% controls), while no CD associations were observed. Sequencing and subsequent genotyping of variants located in this associated haplotype block identified three synonymous variants (D102D/rs224225, G138G/rs224224, A165A/rs224223) and one non-synonymous variant (R202Q/rs224222) located in MEFV exon 2 that were significantly associated with UC (rs224222: p = 0.0005; A allele frequency: 32% in cases, 23% in controls). No consistent associations were observed in additional Canadian (256 CD trios, 91 UC trios) and Scottish (495 UC, 370 controls) sample sets. We note that rs224222 showed marginal association (p = 0.012; G allele frequency: 82% in cases, 70% in controls) in the Canadian sample, but with a different risk allele. None of the NLRP3 common variants were associated with UC in the Belgian-Canadian UC samples and no significant interactions were observed between NLRP3 and MEFV that could explain the observed flip-flop of the rs224222 risk allele. CONCLUSION: The differences in association levels observed between the sample sets may be a consequence of distinct founder effects or of the relative small sample size of the cohorts evaluated in this study. However, the results suggest that common variants in the MEFV region do not contribute to CD and UC susceptibility. [less ▲]Detailed reference viewed: 62 (14 ULg)
Common variants at five new loci associated with early-onset inflammatory bowel disease.
; ; et al
in Nature Genetics (2009), 41(12), 1335-40
The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide ... [more ▼]
The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 x 10(-9)), 22q12 (rs2412973, P = 1.55 x 10(-9)), 10q22 (rs1250550, P = 5.63 x 10(-9)), 2q37 (rs4676410, P = 3.64 x 10(-8)) and 19q13.11 (rs10500264, P = 4.26 x 10(-10)). Our scan also detected associations at 23 of 32 loci previously implicated in adult-onset Crohn's disease and at 8 of 17 loci implicated in adult-onset ulcerative colitis, highlighting the close pathogenetic relationship between early- and adult-onset IBD. [less ▲]Detailed reference viewed: 79 (12 ULg)
Dyspeptic symptoms in the general population: a factor and cluster analysis of symptom groupings.
; ; Louis, Edouard et al
in Neurogastroenterology & Motility : The Official Journal of the European Gastrointestinal Motility Society (2009), 21(4), 378-88
Both dyspeptic and gastro-oesophageal reflux-like symptoms are frequent in the general population, but their degree of overlap is unknown. In severe functional dyspepsia (FD), symptoms are organized in ... [more ▼]
Both dyspeptic and gastro-oesophageal reflux-like symptoms are frequent in the general population, but their degree of overlap is unknown. In severe functional dyspepsia (FD), symptoms are organized in factors associated with pathophysiological mechanisms. The aims of this study were: (i) to assess the prevalence of dyspeptic symptoms with and without overlapping reflux symptoms in the general population and their impact on daily life and on healthcare utilization; and (ii) to compare symptom groupings in the general population to FD patients. A total of 2025 subjects, representative of the Belgian general population, were used in this study. The subjects were submitted to a questionnaire with validated questions on their dyspeptic and reflux symptoms and with evaluators of impact on daily life and use of healthcare resources. Significant dyspeptic symptoms were found in 417 (20.6%). Overlapping reflux symptoms were present in 141 (33.8%). In this group, symptoms were more frequent and more severe. Dyspeptic symptoms induced weight loss (12.7%) and absenteeism (12.4%), affected daily life (61.2%) and generated use of healthcare resources, such as medical consultations (61.4%) and medication (70.9%). Factor analysis revealed a three-component structure with factor 1 including fullness, bloating and early satiety, factor 2 including nausea and vomiting and factor 3 including discomfort, pain, belching and reflux. If forced in a four-factor model, the analysis separates belching as independent factor. Dyspeptic symptoms are frequent in the general population, with overlapping reflux symptoms and increased symptom burden in about a third. [less ▲]Detailed reference viewed: 41 (3 ULg)
Le depistage generalise du cancer colorectal: une absolue necessite et une realite imminente en Communaute francaise.
Polus, Marc ; Montrieux, Christian ; Giet, Didier et al
in Revue Médicale de Liège (2009), 64(2), 96-102
Colorectal cancer is a real problem of public health. Screening is an absolute necessity. An ambitious program of screening is launched in the French Community. Faecal occult blood test will be proposed ... [more ▼]
Colorectal cancer is a real problem of public health. Screening is an absolute necessity. An ambitious program of screening is launched in the French Community. Faecal occult blood test will be proposed to average risk patients in the general population. A total colonoscopy will be performed if FOBT is positive. First step colonoscopy will be proposed to high or very high risk patients. General practitioners are in the core of the multi-disciplinary program. [less ▲]Detailed reference viewed: 72 (10 ULg)
Tailoring the treatment to the individual in Crohn's disease
Louis, Edouard ; Belaiche, Jacques ; Reenaers, Catherine
in Therapeutic advances in Gastroenterology (2009), 2Detailed reference viewed: 15 (0 ULg)
Protéomique par SELDI-TOF-MS des maladies inflammatoires articulaires: identification des protéines S100 comme protéines d'intérêt
De Seny, Dominique ; Ribbens, Clio ; Cobraiville, Gaël et al
in Revue Médicale de Liège (2009), 64(Spec No), 29-35
Clinical proteomics is a technical approach studying the entire proteome expressed by cells, tissues or organs. It describes the dynamics of cell regulation by detecting molecular events related to ... [more ▼]
Clinical proteomics is a technical approach studying the entire proteome expressed by cells, tissues or organs. It describes the dynamics of cell regulation by detecting molecular events related to diseases development. Proteomic techniques focus mainly on identification of new biomarkers or new therapeutic targets. It is a multidisciplinary approach using medical, biological, bioanalytical and bioinformatics knowledges. A strong collaboration between these fields allowed SELDI-TOF-MS proteomics studies to be performed at the CHU and the University of Liege, in GIGA-Research facilities. The aim of these studies was driven along three main axes of research related to the identification of biomarkers specific to a studied pathology, to a common biological pathway and, finally, to a treatment response. [less ▲]Detailed reference viewed: 69 (7 ULg)
Efficacy and safety of a third anti-TNF monoclonal antibody in Crohn's disease after failure of two other anti-TNF.
; ; et al
in Alimentary Pharmacology & Therapeutics (2009)
Adalimumab (ADA) and certolizumab pegol (CZP) have demonstrated efficacy in Crohn's disease (CD) patients previously treated with infliximab (IFX). Aim: To assess the efficacy and tolerability of a third ... [more ▼]
Adalimumab (ADA) and certolizumab pegol (CZP) have demonstrated efficacy in Crohn's disease (CD) patients previously treated with infliximab (IFX). Aim: To assess the efficacy and tolerability of a third anti-TNF in CD after failure of and/or intolerance to two different anti-TNF. Methods: CD patients who received ADA or CZP after loss of response and/or intolerance to two anti-TNF were included in this retrospective study. Data were collected using a standardized questionnaire. Clinical response, duration, safety and reasons for discontinuation were assessed. Results: Sixty-seven patients treated with CZP (n=40) or ADA (n=27) were included. A clinical response was observed in 41 (61%) at week 6 and 34 patients (51%) at week 20. The probability of remaining under treatment at 3 months, 6 months and 9 months was 68%, 60% and 45%, respectively. At the end of follow-up, the third anti-TNF had been stopped in 36 patients for intolerance (n=13), or failure (n=23). Two deaths were observed. Conclusion: Treatment, with a third anti-TNF (CZP or ADA) agent, of CD patients who have experienced loss of response and/or intolerance to two anti-TNF antibodies, has favorable short- and long-term efficacy and is an option to be considered in patients with no other therapeutic options. [less ▲]Detailed reference viewed: 36 (5 ULg)
Evaluation of the GERD Impact Scale, an international, validated patient questionnaire, in daily practice. Results of the ALEGRIA study.
Louis, Edouard ; Tack, Jacques ; et al
in Acta Gastro-Enterologica Belgica (2009), 72(1), 3-8
BACKGROUND AND STUDY AIMS: Gastroesophageal reflux disease (GERD) is a common chronic disease that is primarily diagnosed based on symptom severity and frequency. This study gathered epidemiological data ... [more ▼]
BACKGROUND AND STUDY AIMS: Gastroesophageal reflux disease (GERD) is a common chronic disease that is primarily diagnosed based on symptom severity and frequency. This study gathered epidemiological data in a population of GERD patients and evaluated the added-value of the GERD Impact Scale (GIS), a novel, validated patient questionnaire, as a tool for initial and long-term patient management. PATIENTS AND METHODS: This observational study recruited patients (296 study centers) with symptomatic GERD and a history of erosive, or reflux, esophagitis. Symptoms were assessed by GIS and physician-subject interview and recorded at baseline (visit 1), at 4-6 weeks (visit 2) and 8-14 weeks (visit 3); also recorded at each visit was the physician's assessment of GERD severity and treatment changes. Analyses were performed on an intent-to-treat basis. RESULTS: Subjects (n = 1919; mean age, 55 years) were 54% female. Lifestyle characteristics included stress (approximately 70% of subjects), mean daily consumption of five cups of caffeine-containing beverages (approximately 70%), alcohol consumption of approximately nine units per week (approximately 50%) and smoking/ex-smoker (41%). Proton pump inhibitors were prescribed in 99% of cases: mainly esomeprazole (82%), with a median dose of 40 mg. Prescribed therapy was changed (mainly dosage levels) between visits in approximately 60% of subjects. The severity of GERD symptoms and GIS scores decreased substantially throughout the study. Mean GIS scores correlated positively with increasing GERD severity and clinical judgment at all visits. Physicians reported that the GIS helped them define the appropriate treatment for the patient and to evaluate the patient's response to treatment in 81% of cases. CONCLUSIONS: This study demonstrates the added-value and usefulness of the patient self-assessment GIS as a management tool for GERD. [less ▲]Detailed reference viewed: 70 (0 ULg)
Genetics of ulcerative colitis: the come-back of interleukin 10.
Louis, Edouard ; Libioulle, Cécile ; Reenaers, Catherine et al
in Gut (2009), 58(9), 1173-6Detailed reference viewed: 38 (7 ULg)
Anti-tumor Necrosis Factor Nonresponders in Crohn's Disease : Therapeutic Strategies
Louis, Edouard ; Belaiche, Jacques ; Reenaers, Catherine
in Digestive Diseases (2009), 27Detailed reference viewed: 17 (2 ULg)
Anti-TNF and Crohn's Disease: When Should We Stop?
Louis, Edouard ; Belaiche, Jacques ; Reenaers, Catherine
in Current Drug Targets (2009)
When to stop anti-TNF therapy in Crohn's disease (CD)? This is a very important question both for patients and physicians. There is no published evidence to clearly and definitely answer this question ... [more ▼]
When to stop anti-TNF therapy in Crohn's disease (CD)? This is a very important question both for patients and physicians. There is no published evidence to clearly and definitely answer this question. However data on natural history of CD, long term safety of biologics, outcome after immunosuppressors (IS) cessation and some preliminary studies on biologics cessation may help us to discuss this topic. One could argue that there is currently no good reason to stop anti-TNF therapy in a patient who is in stable remission and tolerate this drug very well. The decision to stop an anti-TNF treatment is thus currently based on a compromise between the benefits/risks and cost of such long term treatment. While it appears now clearly that prolonged anti-TNF therapy is associated with favourable outcome with sustained remission, reduced surgeries and hospitalisation as well as absence of significant increase in mortality or cancers, the cost-effectiveness which is probably favourable for short and mid-term treatment (up to one year), may be less optimal for very long term treatment. In this perspective however, prospective studies should be performed to adequately assess long term evolution, disease outcome, safety and global cost of strategies based on treatment reduction with IS maintenance alone or even full treatment cessation. [less ▲]Detailed reference viewed: 24 (1 ULg)
Thérapies biologiques et maladies inflammatoires chroniques intestinales
Reenaers, Catherine ; Louis, Edouard ; Belaiche, Jacques
in Revue Médicale de Liège (2009), 64(5-6), 301-304Detailed reference viewed: 34 (3 ULg)
Challenges for Biomarker Discovery in Body Fluids Using SELDI-TOF-MS
De Bock, Muriel ; De Seny, Dominique ; Meuwis, Marie-Alice et al
in Journal of Biomedicine & Biotechnology (2009)Detailed reference viewed: 37 (21 ULg)
Gastroenterology - Clinical and genetic factors associated with sacroiliitis in Crohn's disease
; ; et al
in Journal of Gastroenterology and Hepatology (2008), 23(1), 132-137
Background and Aim: Radiographic sacroiliitis (SI), often asymptomatic, is considered the most frequent extra-intestinal manifestation (EIM) of Crohn's disease (CD). Data on the association of SI with ... [more ▼]
Background and Aim: Radiographic sacroiliitis (SI), often asymptomatic, is considered the most frequent extra-intestinal manifestation (EIM) of Crohn's disease (CD). Data on the association of SI with other clinical features of CD are limited. Association of SI with CARD15 polymorphisms has recently been suggested. In a multicenter study, we investigated the association of SI in CD patients with clinical phenotypes, other EIM and CARD15 polymorphisms. Methods: Radiographs of the sacroiliac joints were taken in 251 CD patients from three Belgian university hospitals and scored by two blinded rheumatologists. Clinical features were obtained from medical records. Forty-three percent of patients carried at least one CARD15 polymorphism. Results: Sacroiliitis, defined as the presence of at least grade 2 unilateral changes, was diagnosed in 65 of the 244 scorable radiographs (27%). Only 16 of these patients were previously diagnosed with ankylosing spondylitis (AS). HLA-B27 positivity was observed in 53% of patients with AS and 7% of patients with radiographic SI. In univariate and multivariate analysis, associations between the presence of SI and peripheral arthritis (P = 0.005) and between AS and uveitis (P = 0.005) were found. No associations with other recorded clinical features or with CARD15 polymorphisms were observed. Conclusion: We confirm the high prevalence of radiographic sacroiliitis in a multicenter CD cohort. Uveitis is only associated with AS whereas all patients with SI are more prone to develop peripheral arthritis during their disease course, suggesting similar pathogenetic mechanisms in the development of these EIM. The previously reported association between SI and CARD15 polymorphisms was not confirmed. [less ▲]Detailed reference viewed: 40 (3 ULg)
Proteomics for prediction and characterization of response to infliximab in Crohn's disease: a pilot study.
Meuwis, Marie-Alice ; Fillet, Marianne ; Lutteri, Laurence et al
in Clinical Biochemistry (2008), 41(12), 960-7
OBJECTIVES: Infliximab is the first anti-TNFalpha accepted by the Food and Drug Administration for use in inflammatory bowel disease treatment. Few clinical, biological and genetic factors tend to predict ... [more ▼]
OBJECTIVES: Infliximab is the first anti-TNFalpha accepted by the Food and Drug Administration for use in inflammatory bowel disease treatment. Few clinical, biological and genetic factors tend to predict response in Crohn's disease (CD) patient subcategories, none widely predicting response to infliximab. DESIGN AND METHODS: Twenty CD patients showing clinical response or non response to infliximab were used for serum proteomic profiling on Surface Enhanced Lazer Desorption Ionisation-Time of Flight-Mass Spectrometry (SELDI-TOF-MS), each before and after treatment. Univariate and multivariate data analysis were performed for prediction and characterization of response to infliximab. RESULTS: We obtained a model of classification predicting response to treatment and selected relevant potential biomarkers, among which platelet aggregation factor 4 (PF4). We quantified PF4, sCD40L and IL-6 by ELISA for correlation studies. CONCLUSIONS: This first proteomic pilot study on response to infliximab in CD suggests association between platelet metabolism and response to infliximab and requires validation studies on a larger cohort of patients. [less ▲]Detailed reference viewed: 106 (25 ULg)
Does the phenotype at diagnosis (e.g., fibrostenosing, inflammatory, perforating) predict the course of Crohn's disease?
Louis, Edouard ; Reenaers, Catherine ; Belaiche, Jacques
in Inflammatory Bowel Diseases (2008), 14Detailed reference viewed: 18 (2 ULg)