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See detailMonomeric calgranulins measured by SELDI-TOF mass spectrometry and calprotectin measured by ELISA as biomarkers in arthritis
De Seny, Dominique ULg; Fillet, Marianne ULg; Ribbens, Clio ULg et al

in Clinical Chemistry (2008), 54

BACKGROUND: SELDI-TOF mass spectrometry (MS) is a high-throughput proteomic approach with potential for identifying novel forms of serum biomarkers of arthritis. METHODS: We used SELDI-TOF MS to analyze ... [more ▼]

BACKGROUND: SELDI-TOF mass spectrometry (MS) is a high-throughput proteomic approach with potential for identifying novel forms of serum biomarkers of arthritis. METHODS: We used SELDI-TOF MS to analyze serum samples from patients with various forms of inflammatory arthritis. Several protein profiles were collected on different Bio-Rad Laboratories ProteinChip arrays (CM10 and IMAC-Cu(2+)) and were evaluated statistically to select potential biomarkers. RESULTS: SELDI-TOF MS analyses identified several calgranulin proteins [S100A8 (calgranulin A), S100A9 (calgranulin B), S100A9*, and S100A12 (calgranulin C)], serum amyloid A (SAA), SAA des-Arg (SAA-R), and SAA des-Arg/des-Ser (SAA-RS) as biomarkers and confirmed the results with other techniques, such as western blotting, immunoprecipitation, and nano-LC-MS/MS. The S100 proteins were all able to significantly differentiate samples from patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) from those of patients with inflammatory bowel diseases used as an inflammatory control (IC) group, whereas the SAA, SAA-R, and SAA-RS proteins were not, with the exception of AS. The 4 S100 proteins were coproduced in all of the pathologies and were significantly correlated with the plasma calprotectin concentration; however, these S100 proteins were correlated with the SAA peak intensities only in the RA and IC patient groups. In RA, these S100 proteins (except for S100A12) were significantly correlated with the serum concentrations of C-reactive protein, matrix metalloproteinase 3, and anti-cyclic citrullinated peptide and with the Disease Activity Score (DAS(28)). CONCLUSIONS: The SELDI-TOF MS technology is a powerful approach for analyzing the status of monomeric, truncated, or posttranslationally modified forms of arthritis biomarkers, such as the S100A8, S100A9, S100A12, and SAA proteins. The fact that the SELDI-TOF MS data were correlated with results obtained with the classic calprotectin ELISA test supports the reliability of this new proteomic technique. [less ▲]

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See detailManifestations respiratoires de la rectocolite ulcérohémorragique et de la maladie de Crohn
Guiot, Julien; Louis, Edouard ULg; Belaiche, Jacques ULg et al

in EMC Pneumologie (2008)

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See detailSensitivity of intestinal fibroblasts to TNF-related apoptosis-inducing ligand-mediated apoptosis in Crohn's disease
Reenaers, Catherine ULg; Franchimont, Nathalie; Oury, Cécile ULg et al

in Scandinavian Journal of Gastroenterology (2008), 43

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See detailAn insertion-deletion polymorphism in the Interferon Regulatory Factor 5 (IRF5) gene confers risk of inflammatory bowel diseases
Dideberg, Vinciane ULg; Kristjansdottir, G.; Milani, L. et al

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 ▲]

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See detailAssessment of endoscopic activity lndex and biological lnflammatory markers in clinically active Crohn's disease with normal C-reactive protein serum level
Denis, Marie-Armelle; Reenaers, Catherine ULg; Fontaine, Fernand et al

in Inflammatory Bowel Diseases (2007), 13(9), 1100-1105

Background: Patients with clinically active Crohn's disease (CD), defined by a Crohn's Disease Activity Index (CDAI) > 150, may have normal Greactive protein (CRP) serum levels. In such cases, it is ... [more ▼]

Background: Patients with clinically active Crohn's disease (CD), defined by a Crohn's Disease Activity Index (CDAI) > 150, may have normal Greactive protein (CRP) serum levels. In such cases, it is difficult to know whether these patients have really active disease or rather functional symptoms. This distinction is important to decide the most appropriate treatment. The aim of our work was to assess intestinal and colonic lesions in such patients and to look for biological markers potentially associated with endoscopic activity of the disease. Methods: We included 28 consecutive CD patients with CDAI >150 and a normal CRP level. These patients underwent a full colonoscopy with Crohn's Disease Endoscopy Index of Severity (CDEIS) calculation, fecal calprotectin, blood fibrinogen, acid a-I glycoprotein, and erythrocyte sedimentation rate measurement. The Harvey-Bradshaw score was also calculated. Serum ILI beta, IL6, IL8, sIL2R, and sTNFR2 were measured. Results: The median CDAI was 181 (151-485). Almost all (92.9%) these patients had endoscopic lesions, but the majority had only mild lesions (CDEIS : 6). No correlation was found between CDEIS and any of the clinical or biological markers. However, all the patients with significant endoscopic lesions (defined by a CDEIS >6) had previous surgical intestinal resection and lesions involving the anastomosis. Conclusions: Patients with elevated CDAT and normal CRP have only mild mucosal lesions of CD. Most significant lesions may be observed at the anastomosis and proximal to it in previously operated patients. None of the biological markers tested was associated with these endoscopic lesions. [less ▲]

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See detailThe role of the Toll receptor pathway in susceptibility to inflammatory bowel diseases
De Jager, P. L.; Franchimont, D.; Waliszewska, A. et al

in Genes and Immunity (2007), 8(5), 387-397

The intestinal flora has long been thought to play a role either in initiating or in exacerbating the inflammatory bowel diseases (IBD). Host defenses, such as those mediated by the Toll-like receptors ... [more ▼]

The intestinal flora has long been thought to play a role either in initiating or in exacerbating the inflammatory bowel diseases (IBD). Host defenses, such as those mediated by the Toll-like receptors (TLR), are critical to the host/pathogen interaction and have been implicated in IBD pathophysiology. To explore the association of genetic variation in TLR pathways with susceptibility to IBD, we performed a replication study and pooled analyses of the putative IBD risk alleles in NFKB1 and TLR4, and we performed a haplotype-based screen for association to IBD in the TLR genes and a selection of their adaptor and signaling molecules. Our genotyping of 1539 cases of IBD and pooled analysis of 4805 cases of IBD validates the published association of a TLR4 allele with risk of IBD (odds ratio (OR): 1.30, 95% confidence interval (CI): 1.15 - 1.48; P = 0.00017) and Crohn's disease (OR: 1.33, 95% CI: 1.16 - 1.54; P = 0.000035) but not ulcerative colitis. We also describe novel suggestive evidence that TIRAP (OR: 1.16, 95% CI: 1.04 - 1.30; P = 0.007) has a modest effect on risk of IBD. Our analysis, therefore, offers additional evidence that the TLR4 pathway - in this case, TLR4 and its signaling molecule TIRAP - plays a role in susceptibility to IBD. [less ▲]

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See detailNoninvasive assessment of Crohn's disease intestinal lesions with F-18-FDG PET/CT
Louis, Edouard ULg; Ancion, Geoffrey; Colard, Arnaud et al

in Journal of Nuclear Medicine (2007), 48(7), 1053-1059

Pilot studies have shown good sensitivity and specificity for F-18-FDG PET in detecting gastrointestinal lesions of Crohn's disease. The combination of F-18-FDG PET with CT may further improve the ... [more ▼]

Pilot studies have shown good sensitivity and specificity for F-18-FDG PET in detecting gastrointestinal lesions of Crohn's disease. The combination of F-18-FDG PET with CT may further improve the localization and characterization of lesions with increased F-18-FDG uptake. Our aim was to assess the use of F-18-FDG PET/CT in evaluating the activity and location of Crohn's disease along the gastrointestinal tract. Methods: After giving informed consent, 22 patients with Crohn's disease were prospectively studied. They underwent F-18-FDG PET/CT, followed by ileocolonoscopy within 1 wk (mean, 2 d). The Crohn's disease activity index (CDAI) was calculated, and serum C-reactive protein (CRP) and fecal calprotectin were measured before endoscopy. The Crohn's disease endoscopy index of severity (CDEIS) was calculated during endoscopy. The global CDEIS score and endoscopic subscores for various ileocolonic segments were used for analysis. Results: Globally, 95 intestinal and colonic segments in 22 patients were analyzed. F-18-FDG PET/CT detected 35 of 48 endoscopically affected segments (sensitivity for the detection of endoscopic lesions, 72.9%). The sensitivity of F-18-FDG PET/CT for the detection of severe endoscopic lesions (deep ulcers and strictures) was 100% (14/14). The global PET/CT score significantly correlated with CDEIS (r = 0.51; 95% confidence interval [Cl], 0.09-0.77; P = 0.017), CDAI (r = 0.58; 95% Cl, 0.17-0.80; P = 0.005), and CRP (r = 0.56; 95% Cl, 0.19-0.81; P = 0.007). Conclusion: F-18-FDG PET/CT was globally well correlated to the clinical, endoscopic, and biologic activity of Crohn's disease. Above all, this technique had a good sensitivity for the detection of intestinal and colonic segments with moderate to severe mucosal lesions. The potential impact of this promising tool on the global management of patients with Crohn's disease should be further evaluated in prospective studies. [less ▲]

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See detailThe TNF/ADAM 17 system: implication of an ADAM 17 haplotype in the clinical response to infliximab in Crohn's disease
Dideberg, Vinciane ULg; Theatre, Emilie ULg; Farnir, Frédéric ULg et al

in European Journal of Clinical Investigation (2007, May), 37(Suppl. 1), 79

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See detailMulticenter randomized-control led clinical trial of probiotics (Lactobacillus johnsonii, LA1) on early endoscopic recurrence of Crohn's disease after ileo-caecal resection
Van Gossum, André; Dewit, Olivier; Louis, Edouard ULg et al

in Inflammatory Bowel Diseases (2007), 13(2), 135-142

Background: Seventy percent of Crohn's disease (CD) patients exhibit anastomotic recurrence within I year after ileo-caecal surgery, Recent clinical trials suggest the beneficial use of probiotics in the ... [more ▼]

Background: Seventy percent of Crohn's disease (CD) patients exhibit anastomotic recurrence within I year after ileo-caecal surgery, Recent clinical trials suggest the beneficial use of probiotics in the control of intestinal inflammation in pouchitis and ulcerative colitis. This study is a multicenter clinical trial evaluating the efficacy of an oral administration of the probiotic LA1 on early postoperative endoscopic recurrence of CD. Methods: Seventy patients with CD were enrolled prior to elective ileo-caecal resection and randomly assigned after surgery to daily treatment with either Lactobacillus johnsonii, LA1, Nestle (10(10) colony-forming units, CFU) (group A, n = 34) or placebo (group B, n = 36) for 12 weeks. The primary objective was to assess the effect of LA1 on the endoscopic recurrence rate at 12 weeks. Stratification was performed according to smoking status at randomization. Results: Seven and 14 patients were excluded in the LA1 and placebo groups, respectively. In intention-to-treat analysis, the mean endoscopic score was not significantly different between the two treatment groups at 3 months (LA1 versus placebo: 1.50 +/- 1.32 versus 1.22 +/- 1.37, treatment effect: P = 0.48, smoke effect: P = 0.72). The percentage of patients with severe recurrence (i3 + i4) was 21% and 15% in the LA1 and placebo groups, respectively (P = 0.33). Using a per-protocol (PP) analysis, the mean endoscopic score was not significantly different between the two treatment groups (LA1 versus placebo groups: 1.44 +/- 1.31 versus 1.05 +/- 1.21, P = 0.32). The percentage of patients with severe recurrence (i3 + i4) was 19% and 9% in the LA1 and placebo groups, respectively (P = 0.054). Clinical relapse rate (CDAI [CD activity index] > 150, with an increase of CDAI > 70 points or greater from baseline) in the LAI and placebo groups was 15% (4/27) and 13.5% (3/22), respectively (PP analysis: chi-square test, P = 0.91 and log-rank test: P = 0.79). Conclusion: Oral administration of the probiotic LA1 in patients with CID failed to prevent early endoscopic recurrence at 12 weeks after ileo-caecal resection. [less ▲]

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See detailMultidrug resistance gene-1 polymorphisms and resistance to cyclosporine a in patients with steroid resistant ulcerative colitis
Daniel, F.; Loriot, M. A.; Seksik, P. et al

in Inflammatory Bowel Diseases (2007), 13(1), 19-23

Background: Cyclosporine A (CsA) is inconstantly effective in inducing remission in acute attacks of ulcerative colitis (UC) not responding to steroids. This study aimed to establish whether multidrug ... [more ▼]

Background: Cyclosporine A (CsA) is inconstantly effective in inducing remission in acute attacks of ulcerative colitis (UC) not responding to steroids. This study aimed to establish whether multidrug resistance gene (MDR)1 polymorphisms would be associated with CsA failure. Patients and Methods: The distribution of the different genotypes of single nucleotide polymorphisms (SNP) G2677T/A and C3435T of MDR1 exons 21 and 26, respectively, was studied in 154 patients (mean age, 44 yr) who had received CsA to treat severe attacks of steroid resistant UC in 11 centers in France and Belgium. Patients were classified as CsA failure (n = 50) when they needed colectomy within 30 days after CsA initiation. The SNPs were detected by use of a 5' nuclease allelic discrimination assay. Results: There was a significant association between the G2677T/A polymorphism distribution (exon 21) and the risk for CsA failure (P = 0.0001). The TT genotype of exon 21 was significantly associated with the risk compared with the two other genotypes (odds ratio, 3.77; 95% confidence interval, 1.42-9.97, P = 0.007). There was no significant association between the genotype C3435T distribution (exon 26) and the risk of CsA failure (P = 0.23). Conclusion: The TT genotype of exon 21 MDR1 polymorphisms is associated with a higher risk of CsA failure in patients with steroid resistant UC. Further studies should be performed to establish whether other treatments could be more efficient to avoid surgery in this subset of patients. [less ▲]

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See detailLe depistage du cancer colorectal
Piront, Patricia ULg; Louis, Edouard ULg; Belaiche, Jacques ULg et al

in Revue Médicale de Liège (2007), 62(1), 15-20

Colorectal cancer is the second leading cause of death in Northern countries and need a national screening program to reduce mortality and improve quality of life. Screening has to be cost-effective and ... [more ▼]

Colorectal cancer is the second leading cause of death in Northern countries and need a national screening program to reduce mortality and improve quality of life. Screening has to be cost-effective and acceptable for patients. Many screening tools, invasive or not, are existing and often debated: FOBT, sigmoidoscopy and complete colonoscopy. New tools are in development and have to be evaluated in current practice: virtual colonoscopy, new endoscopic technologies, DNA on faeces or proteomics with markers in serum. [less ▲]

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See detailBiomarker discovery for inflammatory bowel disease, using proteomic serum profiling
Meuwis, Marie-Alice ULg; Fillet, Marianne ULg; Geurts, Pierre ULg et al

in Biochemical Pharmacology (2007), 73(9), 1422-1433

Crohn's disease and ulcerative colitis known as inflammatory bowel diseases (IBD) are chronic immuno-inflammatory pathologies of the gastrointestinal tract. These diseases are multifactorial, polygenic ... [more ▼]

Crohn's disease and ulcerative colitis known as inflammatory bowel diseases (IBD) are chronic immuno-inflammatory pathologies of the gastrointestinal tract. These diseases are multifactorial, polygenic and of unknown etiology. Clinical presentation is non-specific and diagnosis is based on clinical, endoscopic, radiological and histological criteria. Novel markers are needed to improve early diagnosis and classification of these pathologies. We performed a study with 120 serum samples collected from patients classified in 4 groups (30 Crohn, 30 ulcerative colitis, 30 inflammatory controls and 30 healthy controls) according to accredited criteria. We compared protein sera profiles obtained with a Surface Enhanced Laser Desorption Ionization-Time of Flight-Mass Spectrometer (SELDI-TOF-MS). Data analysis with univariate process and a multivariate statistical method based on multiple decision trees algorithms allowed us to select some potential biomarkers. Four of them were identified by mass spectrometry and antibody based methods. Multivariate analysis generated models that could classify samples with good sensitivity and specificity (minimum 80%) discriminating groups of patients. This analysis was used as a tool to classify peaks according to differences in level on spectra through the four categories of patients. Four biomarkers showing important diagnostic value were purified, identified (PF4, MRP8, FIBA and Hpalpha2) and two of these: PF4 and Hpalpha2 were detected in sera by classical methods. SELDI-TOF-MS technology and use of the multiple decision trees method led to protein biomarker patterns analysis and allowed the selection of potential individual biomarkers. Their downstream identification may reveal to be helpful for IBD classification and etiology understanding. [less ▲]

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See detailNovel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4.
Libioulle, Cécile ULg; Louis, Edouard ULg; Hansoul, Sarah ULg et al

in PLoS Genetics (2007), 3(4), 538-543

To identify novel susceptibility loci for Crohn disease (CD), we undertook a genome-wide association study with more than 300,000 SNPs characterized in 547 patients and 928 controls. We found three ... [more ▼]

To identify novel susceptibility loci for Crohn disease (CD), we undertook a genome-wide association study with more than 300,000 SNPs characterized in 547 patients and 928 controls. We found three chromosome regions that provided evidence of disease association with p-values between 10(-6) and 10(-9). Two of these (IL23R on Chromosome 1 and CARD15 on Chromosome 16) correspond to genes previously reported to be associated with CD. In addition, a 250-kb region of Chromosome 5p13.1 was found to contain multiple markers with strongly suggestive evidence of disease association (including four markers with p < 10(-7)). We replicated the results for 5p13.1 by studying 1,266 additional CD patients, 559 additional controls, and 428 trios. Significant evidence of association (p < 4 x 10(-4)) was found in case/control comparisons with the replication data, while associated alleles were over-transmitted to affected offspring (p < 0.05), thus confirming that the 5p13.1 locus contributes to CD susceptibility. The CD-associated 250-kb region was saturated with 111 SNP markers. Haplotype analysis supports a complex locus architecture with multiple variants contributing to disease susceptibility. The novel 5p13.1 CD locus is contained within a 1.25-Mb gene desert. We present evidence that disease-associated alleles correlate with quantitative expression levels of the prostaglandin receptor EP4, PTGER4, the gene that resides closest to the associated region. Our results identify a major new susceptibility locus for CD, and suggest that genetic variants associated with disease risk at this locus could modulate cis-acting regulatory elements of PTGER4. [less ▲]

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See detailCapsule Endoscopy in paediatrics: multicentric Belgian study
Urbain, D.; Tresinie, M.; De Looze, D. et al

in Acta Gastro-Enterologica Belgica (2007), 70(1, JAN-MAR), 11-14

Bacground and study aims : Capsule Endoscopy (CE) is a non-invasive procedure for evaluating small bowel disease. Data concerning children are scarce. The aim of the present report was to review all ... [more ▼]

Bacground and study aims : Capsule Endoscopy (CE) is a non-invasive procedure for evaluating small bowel disease. Data concerning children are scarce. The aim of the present report was to review all paediatric cases investigated by CE in Belgium. Patients and methods : The seven Belgian academic hospitals using the CE device (Given) were asked to collect information on CE performed in patients <= 18 years. Main indications for performing VCE, former radiological and endoscopic procedures were collected, as well as final diagnosis and clinical impact of VCE findings. Results : From November 2002 until December 2005, VCE was performed in 17 children (mean age : 11.9 years, range : 5-18). Indications were occult gastro-intestinal bleeding (OGIB) and/or iron deficiency anaemia (IDA) (10 cases) and chronic and/or recurrent abdominal pain (7 cases). Mean duration of symptoms was 8.6 months. The mean number of endoscopic and radiological procedures before performing CE was 4.2 per patient. Detected lesions were ulcerations (6 cases), jejunal varices (1), ileo-ileal invagination (2), active bleeding (1), and normal findings (7). In the indication of OGIB/IDA, relevant findings having an impact on the diagnosis were found in 60% of the cases. In the group with chronic and recurrent abdominal pain, CE brought relevant findings in 43%. CE findings had an impact on therapy in 44% of the patients. Conclusions : CE could be a useful tool for clinical work-up of difficult paediatric cases, not only in the indication of IDA/OGIB, but also for selected cases of recurrent abdominal pain, but prospective controlled trials including emerging techniques like CT enterography are mandatory. [less ▲]

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See detailScreening for colorectal cancer in 2006
Piront, Patricia ULg; Louis, Edouard ULg; Belaiche, Jacques ULg et al

in Acta Endoscopica (2007), 37(3), 305-313

Colorectal cancer is the second leading cause of death in Northern countries and needs a national screening program to reduce mortality and improve quality of life. Screening has to be cost-effective and ... [more ▼]

Colorectal cancer is the second leading cause of death in Northern countries and needs a national screening program to reduce mortality and improve quality of life. Screening has to be cost-effective and acceptable for patients. Many screening tools, invasive or not, are existing and often debated: FOBT, sigmoidoscopy and complete colonoscopy. New tools are in development and have to be evaluated in current practice: virtual colonoscopy, new endoscopic technologies, DNA on faeces or proteomics with markers in serum. [less ▲]

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See detailPharmacogenetics of infliximab in Crohn's disease
Dideberg, Vinciane ULg; Louis, Edouard ULg; Bours, Vincent ULg

in Acta Endoscopica (2007), 37(4), 521-530

Pharmacogenetic studies will certainly contribute to a better management of medication in inflammatory bowel diseases. Infliximab is the most efficient drug in refractory and fistulising Crohn's disease ... [more ▼]

Pharmacogenetic studies will certainly contribute to a better management of medication in inflammatory bowel diseases. Infliximab is the most efficient drug in refractory and fistulising Crohn's disease. However, about one third of the patients do not respond to this treatment. Several studies have been performed to identify predictive factors of the response to infliximab in CD. We attempt to summarize the current knowledge on the use of infliximab in CD and focus on the result of these studies and more particularly on pharmacogenetic aspects. [less ▲]

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See detailImmunogenicity of infliximab: how to handle the problem?
Baert, Filip; De Vos, Martine; Louis, Edouard ULg et al

in Acta Gastro-Enterologica Belgica (2007), 70(2), 163-70

BACKGROUND: The introduction of infliximab has greatly advanced the therapeutic armamentarium of the inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis. Although the benefit/risk ... [more ▼]

BACKGROUND: The introduction of infliximab has greatly advanced the therapeutic armamentarium of the inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis. Although the benefit/risk ratio for infliximab is positive, of particular concern has been the problem of immunogenicity ascribed to the chimeric properties of the drug. Antibody formation is associated with allergic reactions and loss of response. AIMS AND METHODS: A literature search was undertaken on the magnitude of the problem of immunogenicity and on the clinical consequences. A survey was conducted about the clinical practice and management of acute and delayed allergic reactions to infliximab in different centres in Belgium. For this, a questionnaire was sent to all members of the Belgian IBD research group (n = 38 belonging to 29 centers). RESULTS AND CONCLUSION: Infusion reactions are important immunologic events induced by the presence of a substantial concentration of antibodies against infliximab (ATI) in the serum. Concomitant immunosuppressive treatment may optimize response to infliximab by preventing the formation of antibodies. Steroid administration prior to an infliximab infusion can further reduce the immunogenicity. Probably the most effective strategy to optimize treatment and avoid immunogenicity is maintenance therapy. If infliximab therapy can be discontinued is yet unclear but when treatment goals have been reached, we feel this should be attempted. In the case of relapse, infliximab should be restarted as maintenance long term. Practical guidelines on how to handle the problem of immunogenicity to infliximab are important for clinicians treating patients with IBD. [less ▲]

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See detailTreatment of small bowel subocclusive Crohn's disease with infliximab: an open pilot study
Louis, Edouard ULg; Boverie, Jacques ULg; Dewit, Olivier et al

in Acta Gastro-Enterologica Belgica (2007), 70(1, Jan-Mar), 15-19

Stricturing subocclusive small bowel Crohn's disease (CD) is often an indication for surgery. We embarked on an open label pilot study to assess the safety and efficacy of infliximab in patients with ... [more ▼]

Stricturing subocclusive small bowel Crohn's disease (CD) is often an indication for surgery. We embarked on an open label pilot study to assess the safety and efficacy of infliximab in patients with stricturing subocclusive CD. Patients and methods : A cohort of patients with a documented and symptomatic small bowel stricture caused by CD was studied. Patients had to be refractory to corticosteroids and/or immunosuppressives, and not in need for immediate surgery. The patients were treated by a single infusion of infliximab 5 mg/kg and followed up at w1, w2, w4 and w8. Results : After the 6(th) patients, the study was prematurely discontinued because the predefined safety thresholds of more than 2 surgeries within the first 5 patients was reached. Only two patients completed the 8 weeks study, with a positive response to infliximab and improvement of inflammation confirmed by the CRP and CT scan. Two patients had to be operated early and the last two patients first did well but worsened after one month and were operated 35 and 42 days after infliximab, respectively. No surgical complications occurred in the 4 operated patients. In conclusion, a subset of patients with subocclusive small bowel stricturing CD may benefit from infliximab. [less ▲]

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See detailActualites therapeutiques en hepato-gastroenterologie
Belaiche, Jacques ULg; Delwaide, Jean ULg; Polus, Marc ULg et al

in Revue Médicale de Liège (2007), 62(5-6, May-Jun), 303-9

During the last decade, advances in molecular biology and biotechnology allowed, the development of biological treatments aimed at more precise targets. New algorithms in inflammatory bowel diseases ... [more ▼]

During the last decade, advances in molecular biology and biotechnology allowed, the development of biological treatments aimed at more precise targets. New algorithms in inflammatory bowel diseases, chronic hepatitis C and digestive oncology are examples of the marked progress achieved by these therapies. [less ▲]

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