Severine Vermeire

..Nevertheless, these markers are often negative in this setting. The interest in antimicrobial and antiglycan antibodies has recently been increased as they have shown to act as surrogate markers of complicated aggressive disease...

..Only then could the value of molecular markers to predict the speed of progression be fully explored in prospective studies...

..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...

..Until there are more data, the use of CRP and of other biomarkers should be seen as an additional tool that aids clinical observation and physical examination, but that cannot replace it...

..Overall, it is anticipated that genetic markers in the future will be implemented in an integrated molecular diagnostic and prognostic approach of our patients...

..Efforts to predict disease course and response to therapy have shown interesting results...

..We studied mutation prevalence, assessed phenotypic expression, and performed conditional analysis to examine evidence for gene-gene interactions...

..Major advances in treatment options over the past years have made our treatment goals more ambitious and modification of the natural course has become the ultimate endpoint...

..They are however not magic and until more data become available, the use of CRP and other laboratory markers should be seen as an additive tool to clinical observation and physical examination rather than a replacement...

..We discuss the safety aspects of the biological agents in this chapter and, where available, give ways to prevent and/or treat them...

..The previous 18 months have shown important progress in unravelling the causes of inflammatory bowel disease (IBD) and in improving its management for the patients...

..This first-in-human study of a monoclonal antibody to MAdCAM, PF-00547,659, aimed to explore the safety and preliminary efficacy of this gut-specific mechanism in ulcerative colitis...

..In the future, it is anticipated that genetic markers will be implemented in an integrated molecular diagnostic and prognostic approach to managing our patients...

..This review analyses and discusses current classifications of any perianal form of Crohn's disease...

..Nevertheless, the importance and necessity of pharmacogenetic studies will increase further as more therapeutic classes are being developed...

..We investigated whether a simpler tool, the Harvey-Bradshaw Index, was equally effective in assessing disease severity...

..However, currently, they have no place in the diagnostic work up. Their real promise may lie in their use as surrogate markers of complicated aggressive disease as shown in various retrospective studies, but prospective data are lacking...

..Finally, screening unaffected relatives of CD patients is not recommended until preventive strategies are available...

..We aimed to study the influence of immunosuppressives discontinuation in patients in remission with combination therapy in an open-label, randomized, controlled trial...

..Materials and..

..This migration is regulated by cell adhesion molecules (CAMs), and selective antimigration therapies have been developed. This study investigated the effect of infliximab therapy on the mucosal gene expression of CAMs in IBD...

..6%, respectively, p<0.0001) and more often had concomitant immune-mediated diseases and a trend for more seroreactivity towards ASCA...

..We observed two main staining patterns, both of which were present in IBD and were associated with specific phenotypes of the disease...

..Since nothing is known about the transmission of these variants within families, this was the subject of our study in Flemish patients with inflammatory bowel disease (IBD) and their healthy relatives...

..Genetic variants in autophagy genes IRGM and ATG16L1 have been associated with susceptibility to Crohn's disease. We therefore investigated whether variants in autophagy genes contribute to granuloma formation...

..The histological features in the liver of PSC patients are similar to those observed in cystic fibrosis (CF). Our aim was to study whether variants in the CFTR gene are associated with the occurrence and/or evolution of PSC...

..We investigated the impact of anti-inflammatory therapy with infliximab on the mucosal gene expression of AMPs in IBD...

..To focus on the emerging clinical evidence for the use of traditional immunosuppressives and biologicals in the treatment of inflammatory bowel disease...

..Few prospective data are available to support the clinical relevance of mucosal healing in patients with Crohn's disease. This study examined whether complete healing, determined by endoscopy, predicts a better outcome in Crohn's disease...

..However, a subset of patients shows incomplete or no response to this agent. In this study we investigated whether we could identify a mucosal gene panel to predict (non)response to IFX in CD...

..This is underscored by the finding of the association between CARD15 variants and Crohn's disease (CD) and D299G in Toll-like receptor (TLR) 4 and IBD. Our aims were to study nonsynonymous polymorphisms in other TLR genes in IBD...

..We aimed to investigate the predictive role of serologic and histologic markers on disease relapse in UC patients with endoscopically inactive disease...

..Therefore, patients not responding to these agents within 5-7 d should be considered for colectomy and responders should be closely monitored for infections...

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..In case reports, thiopurine analogs and infliximab (IFX) have been proposed as effective therapy in this setting. We analyzed the long-term efficacy of IFX in Belgian patients with refractory pouch complications...

..C-reactive protein (CRP) is a marker used to identify and follow individuals with CD. We analyzed changes in levels of CRP in a large cohort of patients with CD undergoing treatment with infliximab...

..Infliximab (IFX) treatment induces mucosal healing (MH) in patients with Crohn's disease (CD) but the impact of MH on the long-term outcome of IFX treatment in CD is still debated...

..Moreover, serum VEGF (sVEGF) levels are increased in IBD and correlate with disease activity. Both VEGF expression and sVEGF levels may be influenced by VEGF gene polymorphisms...

..Concomitant use of immunosuppressives (IS) reduces the risk of ATI formation...

..In this study we measured colonic mucosal TST enzyme activity and gene expression in UC and controls. In addition, the influence of sulfides on butyrate oxidation was evaluated...

..However, whether we need to include CRP as an inclusion criterion for future trials with biologicals is still a matter of debate...

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..CONCLUSIONS: In this large cohort of infliximab-treated CD patients, young age, Crohn's colitis, and concomitant immunosuppressive treatment were identified as independent variables favoring short-term response to infliximab...

..Our purpose was to determine whether single nucleotide polymorphisms (SNPs) in the TNF receptors confer susceptibility to Crohn's disease and whether they are associated with clinical phenotype...

..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...

..We examined the influence of recently discovered CD-associated susceptibility loci on changes in disease behavior and evaluated whether a genetic risk model for disease progression could be generated...

..In clinical practice assessing mucosal healing should be considered in patients with persistent symptoms despite adequate therapy and when treatment discontinuation is being considered...

..Therefore, we investigated the effect of infliximab (IFX) therapy on Forkhead box protein3 (Foxp3) T cells in blood and intestinal mucosa from Crohn's disease (CD) and ulcerative colitis (UC)...

..CONCLUSIONS: CSA is an effective treatment of the majority of patients with severe attacks of UC, although the toxicity and even mortality associated with its use necessitates careful evaluation, selection, and follow-up...

..We investigated the efficacy and safety of ornidazole, a nitroimidazole antibiotic, for the prevention of clinical recurrence of Crohn's disease after curative ileocolonic resection in a placebo-controlled double-blind clinical trial...

..Patients with inflammatory bowel disease (IBD) carry autoantibodies such as perinuclear antineutrophil cytoplasmic antibodies. The aim of the current study was to further characterize the immune reactivity in IBD...

..Infliximab (IFX) and adalimumab (ADA) are attractive treatment options in patients with inflammatory bowel disease (IBD) also during pregnancy but there is still limited data on the benefit/risk profile of IFX and ADA during pregnancy...

..Expression is localized in B cells, suggesting that IL-15 regulates B-cell functions during bowel inflammation. No change in release of sIL-15Rα is observed in patients treated with IFX...

..Objectives: We investigated whether genomic copy number variations of the beta-defensin gene cluster have a functional role in airway epithelial cells and associate with the presence of COPD...

..The primary end point was the incidence of infusion reactions in both groups...

..Whether dysbiosis is present in relatives of patients CD was also examined...

..Two patients developed drug-induced lupus erythematosus. Antinuclear antibodies were associated with the female sex and skin manifestations...

..Our objective is to report the outcome of infliximab (IFX) in ulcerative colitis (UC) patients from a single center and to identify predictors of early clinical response...

..Predictors of response could improve selection of patients with a higher probability of favorable outcomes and could improve the safety profile. We aimed to develop a predictive model for the response to infliximab in CD...

..Goal: We sought to examine whether metronidazole for 3 months together with azathioprine (AZA) for 12 months is superior to metronidazole alone to reduce recurrence of postoperative CD in "high-risk" patients...

..CONCLUSIONS: CSA is an effective short- to medium-term treatment for patients with severe UC but at 7 years, 88% of patients will require a colectomy. Azathioprine-naive patients have better outcomes...

..Finally, it remains unclear if and when a biologic agent can be stopped in patients with long-standing remission...

..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...

..Concomitant immunosuppressive therapy reduces the magnitude of the immunogenic response...

..Other adverse events associated with anti-TNF strategies are demyelinating disease and worsening of congestive heart failure. Malignancy rates in patients treated with anti-TNF strategies do not seem to be increased...

..It is not clear which factors influence treatment outcome. We assessed whether variants in NOD2/CARD15 are predictive for differences in clinical response...

..During the course of their disease, about 30% of patients with ulcerative colitis (UC) will undergo proctocolectomy with ileal pouch-anal anastomosis (IPAA). We evaluated the outcome of IPAA in a Belgian referral center...

..Whereas the validity and reproducibility of the IBDQ have been extensively studied, there are limited data on its short-term responsiveness and cutoff values for remission and partial clinical response...

..An effort should be made to collect genomic DNA from all patients enrolled in clinical drug trials after appropriate informed consent for pharmacogenetic studies...

..We investigated the role of antimicrobial and antiglycan antibodies and polymorphisms in microbial pattern recognition receptor genes...

..We propose that future studies should focus on healing and disease course as primary outcome measures...

..Antibody formation is associated with allergic reactions and loss of response...

..alpha-Enolase has been proposed as a target antigen in IBD. We evaluated the prevalence and diagnostic value of anti-alpha-enolase antibodies in IBD and related disorders...

..The optimal prediction of both disease behaviour and response to therapy might result from complex combinations of clinical, biochemical, serological and genetic factors...

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..Despite the advent of the anti-TNF agent, infliximab, an important unmet medical need characterizes the medical treatment of inflammatory bowel diseases. This review aims to summarize recent progress in the field...

..Some studies suggested an association between the month of birth and the later development of IBD. We studied this putative relationship in a large cohort of Belgian patients with Crohn's disease (CD)...

..Our single center, randomized, double-blind, controlled trial aimed to evaluate the additional clinical benefit of 4 mg/kg over 2 mg/kg IV cyclosporine in the acute treatment of severe UC...

..As illustrated by unexpected but devastating brain infections with anti-adhesion molecules, clinicians should be aware that the powerful immunomodulatory capacity of biologicals necessitates a rigorous safety follow-up...

..The efficacy of each therapy must be shown in carefully designed clinical programs. Biological therapies carry a definite safety risk, so their place in treatment algorithms must be defined carefully...

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..Whereas prolonged exposure to steroids predisposes to an increased rate of peri-operative complications it is still debated whether cyclosporine or infliximab increase peri-operative morbidity in ulcerative colitis...

..The purpose of this review is to summarize recent evidence describing specific complications associated with the use of biological therapy derived from controlled trials and from post-marketing surveillance...

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..Our aim was to study the influence of single nucleotide polymorphisms in selected genes involved in innate immunity on the development of bacteremia or risk of death in patients admitted to a medical intensive care unit...

..We therefore investigated the role of the functional 32-bp deletion in this gene (CCR5-Delta32) with regard to susceptibility to PSC...

..In this family the father developed Crohn's disease (CD) after moving from Morocco to Belgium and successively 4 of his 8 children subsequently developed CD. There was no previous history of familial CD...

..Studies have revealed associations between polymorphisms in TLRs and human diseases. The effect of polymorphisms in TLR2 and TLR4 in the human defense to S. pneumoniae has not been studied...