References of "Van Steen, Kristel"
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See detailLevels of C-reactive protein are associated with response to infliximab therapy in patients with Crohn's disease.
Jurgens, Matthias; Mahachie John, Jestinah ULg; Cleynen, Isabelle et al

in Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of The American Gastroenterological Association (2011), 9(5), 421-71

BACKGROUND & AIMS: Infliximab is an antibody against tumor necrosis factor-alpha that is used to treat patients with moderate to severe Crohn's disease (CD). C-reactive protein (CRP) is a marker used to ... [more ▼]

BACKGROUND & AIMS: Infliximab is an antibody against tumor necrosis factor-alpha that is used to treat patients with moderate to severe Crohn's disease (CD). 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. METHODS: Serial levels of CRP were analyzed in 718 CD patients. Blood was collected before each infusion; a total of 8845 CRP levels were available for analysis. The correlations between CRP levels and need for dose adjustment, outcomes, and mucosal healing (based on endoscopic analysis of 253 patients) were evaluated. Therapy adjustment was considered successful if therapy continued without need for change. Subgroup analysis was performed by using data from 268 patients who received 8 weeks of maintenance therapy. RESULTS: More patients with high baseline levels of CRP responded to infliximab than patients with normal levels (90.8% vs 82.6%; P = .014). Early normalization of CRP levels correlated with sustained long-term response (P < .001). CRP levels remained significantly higher among patients who lost their response to infliximab, compared with those with a sustained response (P = .001). At time of loss of response, CRP levels were significantly increased (median, 11.2 mg/L) and did not return to baseline levels (median, 18.2 mg/L; P = .039). CRP correlated with mucosal healing (P = .033). CONCLUSIONS: CRP is a good marker of disease activity in patients treated with infliximab. Increased levels of CRP indicate mucosal inflammation and a likelihood of clinical relapse. [less ▲]

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See detailIdentification of a novel autoantigen in inflammatory bowel disease by protein microarray.
Vermeulen, Nathalie; de Beeck, Katrijn Op; Vermeire, Severine et al

in Inflammatory Bowel Diseases (2011), 17(6), 1291-300

BACKGROUND: Patients with inflammatory bowel disease (IBD) display immunoreactivity to self-antigens and microbial antigens. We used a protein microarray approach to identify novel autoantigens in IBD ... [more ▼]

BACKGROUND: Patients with inflammatory bowel disease (IBD) display immunoreactivity to self-antigens and microbial antigens. We used a protein microarray approach to identify novel autoantigens in IBD. METHODS: ProtoArray Human Protein Microarray v4.0 containing 8268 human proteins from Invitrogen (La Jolla, CA) was used. RESULTS: Twenty-five IBD patients and five healthy controls were screened for candidate autoantigens. For 256 antigens, IBD patients had a higher seroreactivity than controls. Twenty antigens were selected for further evaluation in a larger cohort (60 ulcerative colitis [UC] patients, 60 Crohn's disease [CD] patients, 60 healthy controls, and 60 gastrointestinal-diseased controls) by means of a customized protein microarray. Out of these 20 antigens, one antigen, family with sequence similarity 84 member A (FAM84A), was identified as a target antigen in IBD. Antibodies to FAM84A were significantly more prevalent in IBD patients (19%) than in gastrointestinal-diseased controls (1.7%) (P = 0.0008) and healthy controls (5%) (P = 0.01). Anti-FAM84A antibodies were found in 26.6% of UC patients and in 11.7% of CD patients. FAM84A was confirmed as target antigen in IBD by means of Western blotting in a large independent cohort (100 UC patients, 106 CD patients, 102 healthy controls, and 100 gastrointestinal-diseased controls). Antibodies to FAM84A were significantly more prevalent in IBD patients (20%) than in gastrointestinal-diseased controls (5%) (P = 0.0004) and healthy controls (0%) (P < 0.0001). Anti-FAM84A antibodies were found in 18% of UC patients and in 22% of CD patients. CONCLUSIONS: We identified FAM84A as a novel autoantigen in IBD. (Inflamm Bowel Dis 2011;). [less ▲]

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See detailInvestigating Hardy-Weinberg equilibrium in case-control or cohort studies or meta-analysis.
Ziegler, Andreas; Van Steen, Kristel ULg; Wellek, Stefan

in Breast Cancer Research and Treatment (2011), 128(1), 197-201

Yu et al. (Breast Cancer Res Treat 117:675-677, 2009) recently stated that testing for deviation from Hardy-Weinberg equilibrium (HWE) is necessary to identify systematic genotyping errors in case-control ... [more ▼]

Yu et al. (Breast Cancer Res Treat 117:675-677, 2009) recently stated that testing for deviation from Hardy-Weinberg equilibrium (HWE) is necessary to identify systematic genotyping errors in case-control studies. They criticized a meta-analytic study for the deviation from HWE in the case group of one study. The aim of this article is twofold. First, we derive recommendations on how to test for deviations from HWE in different study designs. Second, we develop a meta-analytic framework for assessing compatibility with HWE or measuring deviation from HWE. The authors sketch the possible reasons behind deviation from HWE and provide guidelines for proper investigation of HWE deviations in different study designs. The authors argue that the standard HWE chi(2) lack of fit test is logically flawed and provide a logically unflawed approach for measuring deviation from HWE using confidence intervals. The proposed method is applicable to meta-analyses of both case-control or cohort association studies. The proposed approach is illustrated using the meta-analysis criticized by Yu et al. Heterogeneity between studies can be assessed. The critique of Yu et al. to the article of Frank et al. (Breast Cancer Res Treat 111:139-144, 2008) can be refuted. Even more, validity of HWE can be proven for the pooled control sample. The authors advocate the use of a confidence interval-based approach to assess HWE. The latter should only be investigated in control populations. In multicenter studies or meta-analysis, deviation from HWE should be analyzed using a meta-analytic approach. [less ▲]

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See detailMepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis.
Gevaert, Philippe; Van Bruaene, Nicholas; Cattaert, Tom ULg et al

in Journal of Allergy and Clinical Immunology (The) (2011), 128(5), 989-9958

BACKGROUND: Approximately 85% of nasal polyps (NPs) in white subjects are characterized by prominent eosinophilia. IL-5 is the key driver of eosinophilic differentiation and survival. OBJECTIVE: We sought ... [more ▼]

BACKGROUND: Approximately 85% of nasal polyps (NPs) in white subjects are characterized by prominent eosinophilia. IL-5 is the key driver of eosinophilic differentiation and survival. OBJECTIVE: We sought to investigate the therapeutic potential of inhibiting IL-5 with a humanized mAb as treatment for severe nasal polyposis. METHODS: Thirty patients with severe nasal polyposis (grade 3 or 4 or recurrent after surgery) refractory to corticosteroid therapy were randomized in a double-blind fashion to receive either 2 single intravenous injections (28 days apart) of 750 mg of mepolizumab (n = 20) or placebo (n = 10). Change from baseline in NP score was assessed monthly until 1 month after the last dose (week 8). Computed tomographic scans were also performed at week 8. RESULTS: Twelve of 20 patients receiving mepolizumab had a significantly improved NP score and computed tomographic scan score compared with 1 of 10 patients receiving placebo at week 8 versus baseline. CONCLUSION: Mepolizumab achieved a statistically significant reduction in NP size for at least 1 month after dosing in 12 of 20 patients. IL-5 inhibition is a potential novel therapeutic approach in patients with severe eosinophilic nasal polyposis. [less ▲]

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See detailFamilial aggregation and antimicrobial response dose-dependently affect the risk for Crohn's disease.
Joossens, Marie; Van Steen, Kristel ULg; Branche, Julien et al

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 Belgium 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, NOD1, TLR4, CARD8) and serologic markers (ASCA, ACMA, ALCA, ACCA, ASigmaMA, 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. Inflamm Bowel Dis 2010. [less ▲]

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See detailMulticollinearity
Van Steen, Kristel ULg; Molenberghs, G.

in Chow (Ed.) Encyclopedia of Biopharmaceutical Statistics (2010)

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See detailLongitudinal study of European birth cohorts on pet ownership up to age 10 years as a risk for childhood asthma - a GA²LEN project
Mahachie John, Jestinah ULg; Roll, S.; Lau, S. et al

in European Respiratory Journal. Supplement (2010), 36(supplement 54),

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See detailPredictive value of epithelial gene expression profiles for response to infliximab in Crohn’s disease
Arijs, Ingrid; Quintens, Roel; Van Lommel, Leentje et al

in Inflammatory Bowel Diseases (2010), 16(12), 2090-2098

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See detailPresence of IL-5 and Ige-antibodies to staphylococcal enterotoxins in nasal polyps is associated with co-morbid asthma
Bachert, Claus; Zhang, Nan; Holtappels, Gabriele et al

in Journal of Allergy and Clinical Immunology (The) (2010), 126(5), 962-968

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See detailMolecular Reclassification of Crohn’s Disease by cluster analysis of genetic variants.
Cleynen, I.; Mahachie John, Jestinah ULg; Henckaerts, Liesbet et al

in Acta Gastro-Enterologica Belgica (2010)

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See detailTolerability of shortened infliximab infusion times in patients with inflammatory bowel disease: a single center cohort study
Breynaert, C; Ferrante, F; Fidder, H et al

in Gut (2010)

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See detailIntestinal mucosal gene expression of endothelial cell adhesion molecules in patients with inflammatory bowel disease before and after first infliximab treatment.
Arijs, Ingrid; Quintens, Roel; Lemaire, Katleen et al

in Acta Gastro-Enterologica Belgica (2010)

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See detailThe impact of infliximab therapy on intestinal mucosal gene expression of endothelial cell adhesion molecules in patients with inflammatory bowel disease
Arijs, I.; Quintens, R.; Lemaire, K. et al

in Gastroenterology (2010), 138(5 Suppl I), -677

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See detailA screening methodology based on Random Forests to improve the detection of gene-gene interactions
De Lobel, L.; Geurts, Pierre ULg; Baele, G. et al

in European Journal of Human Genetics (2010), 18(1127), 1132

The search for susceptibility loci in gene-gene interactions imposes a methodological and computational challenge for statisticians because of the large dimensionality inherent to the modelling of gene ... [more ▼]

The search for susceptibility loci in gene-gene interactions imposes a methodological and computational challenge for statisticians because of the large dimensionality inherent to the modelling of gene-gene interactions or epistasis. In an era in which genome-wide scans have become relatively common, new powerful methods are required to handle the huge amount of feasible gene-gene interactions and to weed out false positives and negatives from these results. One solution to the dimensionality problem is to reduce data by preliminary screening of markers to select the best candidates for further analysis. Ideally, this screening step is statistically independent of the testing phase. Initially developed for small numbers of markers, the Multifactor Dimensionality Reduction (MDR) method is a nonparametric, model-free data reduction technique to associate sets of markers with optimal predictive properties to disease. In this study, we examine the power of MDR in larger data sets and compare it with other approaches that are able to identify gene-gene interactions. Under various interaction models (purely and not purely epistatic), we use a Random Forest (RF)-based prescreening method, before executing MDR, to improve its performance. We find that the power of MDR increases when noisy SNPs are first removed, by creating a collection of candidate markers with RFs. We validate our technique by extensive simulation studies and by application to asthma data from the European Committee of Respiratory Health Study II.European Journal of Human Genetics advance online publication, 12 May 2010; doi:10.1038/ejhg.2010.48. [less ▲]

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See detailKinetics of C-Reactive Protein (CRP) following maintenance infliximab treatment in Crohn's disease identifies profiles of patients with better outcome
Jürgens, M.; Mahachie John, Jestinah ULg; Cleynen, I. et al

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

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See detailIn utero smoke exposure and impaired response to inhaled corticosteroids in children with asthma
Cohen, Robyn T.; Raby, Benjamin A.; Van Steen, Kristel ULg et al

in Journal of Allergy and Clinical Immunology (The) (2010), 126(3), 491-497

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See detailIntestinal mucosal gene expression of endothelial cell adhesion molecules in patients with inflammatory bowel disease and the impact of infliximab therapy.
Arijs, Ingrid; Quintens, Roel; Lemaire, Katleen et al

in Journal of Crohn’s and Colitis [=JCC] (2010)

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See detailmbmdr: an R package for exploring gene-gene interactions associated with binary or quantitative traits
Calle, M. Luz; Urrea, Victor; Van Steen, Kristel ULg

in Bioinformatics (2010), 26(17), 2198-2199

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See detailMolecular Reclassification of Crohn's Disease by Cluster Analysis of Genetic Variants
Cleynen, Isabelle; Mahachie John, Jestinah ULg; Henckaerts, Liesbet et al

in PLoS ONE (2010), 5(9), 12952

<sec> <title>Background</title> <p>Crohn's Disease (CD) has a heterogeneous presentation, and is typically classified according to extent and location of disease. The genetic susceptibility to CD is well ... [more ▼]

<sec> <title>Background</title> <p>Crohn's Disease (CD) has a heterogeneous presentation, and is typically classified according to extent and location of disease. The genetic susceptibility to CD is well known and genome-wide association scans (GWAS) and meta-analysis thereof have identified over 30 susceptibility loci. Except for the association between ileal CD and <italic>NOD2</italic> mutations, efforts in trying to link CD genetics to clinical subphenotypes have not been very successful. We hypothesized that the large number of confirmed genetic variants enables (better) classification of CD patients.</p> </sec><sec> <title>Methodology/Principal Findings</title> <p>To look for genetic-based subgroups, genotyping results of 46 SNPs identified from CD GWAS were analyzed by Latent Class Analysis (LCA) in CD patients and in healthy controls. Six genetic-based subgroups were identified in CD patients, which were significantly different from the five subgroups found in healthy controls. The identified CD-specific clusters are therefore likely to contribute to disease behavior. We then looked at whether we could relate the genetic-based subgroups to the currently used clinical parameters. Although modest differences in prevalence of disease location and behavior could be observed among the CD clusters, Random Forest analysis showed that patients could not be allocated to one of the 6 genetic-based subgroups based on the typically used clinical parameters alone. This points to a poor relationship between the genetic-based subgroups and the used clinical subphenotypes.</p> </sec><sec> <title>Conclusions/Significance</title> <p>This approach serves as a first step to reclassify Crohn's disease. The used technique can be applied to other common complex diseases as well, and will help to complete patient characterization, in order to evolve towards personalized medicine.</p> </sec> [less ▲]

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See detailFAM-MDR: A Flexible Family-Based Multifactor Dimensionality Reduction Technique to Detect Epistasis Using Related Individuals
Cattaert, Tom ULg; Urrea, V.; Naj, A. C. et al

in PLoS ONE (2010), 5(4), -

We propose a novel multifactor dimensionality reduction method for epistasis detection in small or extended pedigrees, FAM-MDR. It combines features of the Genome-wide Rapid Association using Mixed Model ... [more ▼]

We propose a novel multifactor dimensionality reduction method for epistasis detection in small or extended pedigrees, FAM-MDR. It combines features of the Genome-wide Rapid Association using Mixed Model And Regression approach (GRAMMAR) with Model-Based MDR (MB-MDR). We focus on continuous traits, although the method is general and can be used for outcomes of any type, including binary and censored traits. When comparing FAM-MDR with Pedigree-based Generalized MDR (PGMDR), which is a generalization of Multifactor Dimensionality Reduction (MDR) to continuous traits and related individuals, FAM-MDR was found to outperform PGMDR in terms of power, in most of the considered simulated scenarios. Additional simulations revealed that PGMDR does not appropriately deal with multiple testing and consequently gives rise to overly optimistic results. FAM-MDR adequately deals with multiple testing in epistasis screens and is in contrast rather conservative, by construction. Furthermore, simulations show that correcting for lower order (main) effects is of utmost importance when claiming epistasis. As Type 2 Diabetes Mellitus (T2DM) is a complex phenotype likely influenced by gene-gene interactions, we applied FAM-MDR to examine data on glucose area-under-the-curve (GAUC), an endophenotype of T2DM for which multiple independent genetic associations have been observed, in the Amish Family Diabetes Study (AFDS). This application reveals that FAM-MDR makes more efficient use of the available data than PGMDR and can deal with multi-generational pedigrees more easily. In conclusion, we have validated FAM-MDR and compared it to PGMDR, the current state-of-the-art MDR method for family data, using both simulations and a practical dataset. FAM-MDR is found to outperform PGMDR in that it handles the multiple testing issue more correctly, has increased power, and efficiently uses all available information. [less ▲]

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