References of "De Hertogh, G"
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See detailLoss of T cell microRNA provides systemic protection against autoimmune pathology in mice
Tian, L.; De Hertogh, G.; Fedeli, M. et al

in Journal of Autoimmunity (2012)

With an increasing number of studies demonstrating alterations in T cell microRNA expression during autoimmune disease, modulation of the T cell microRNA network is considered a potential therapeutic ... [more ▼]

With an increasing number of studies demonstrating alterations in T cell microRNA expression during autoimmune disease, modulation of the T cell microRNA network is considered a potential therapeutic strategy. Due to the complex and often opposing interactions of individual microRNA, prioritization of therapeutic targets first requires dissecting the dominant effects of the T cell microRNA network. Initial results utilizing a unidirectional screen suggested that the tolerogenic functions were dominanat, with spontaneous colitis resulting from T cell-specific excision of Dicer. Here we performed a bidirectional screen for microRNA function by removing Dicer from the T cells of both wildtype mice and Transforming Growth Factor β (TGFβ) receptor-deficient mice. This allowed the impact of microRNA loss on T cell activation, effector T cell differentiation and autoimmune pathology to be systematically assessed. This bidirectional screen revealed a dominant immunogenic functionfor T cell microRNA, with potent suppression of T cell activation, IFNγ production and autoimmune pathology in all targeted organs except the colon, where Dicer-dependent microRNA demonstrated a dominant tolerogenic function. These results reverse the original conclusions of microRNA function in T cells by revealing a systemic pro-autoimmune function. [less ▲]

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See detailEffects of haptoglobin polymorphisms and deficiency on susceptibility to inflammatory bowel disease and on severity of murine colitis.
Marquez, L.; Shen, C.; Cleynen, I. et al

in Gut (2011), 61(4), 528-534

BackgroundHaptoglobin (Hp) is a haemoglobin-binding protein with immunomodulatory properties. Its gene (16q22) harbours a common polymorphism with two different alleles: Hp1 and Hp2. Genotype Hp22 has ... [more ▼]

BackgroundHaptoglobin (Hp) is a haemoglobin-binding protein with immunomodulatory properties. 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.AimsTo determine whether Hp plays a role in inflammatory bowel disease, both genetically and functionally.Methods1061 patients with CD, 755 with ulcerative colitis (UC) and 152 with primary sclerosing cholangitis, as well as 452 healthy controls, were genotyped using touch-down PCR. To confirm association results, 464 CD trios and 151 UC trios were genotyped. Serum Hp concentrations were determined in 62 individuals of different genotype. Colitis was induced in mice with dextran sulphate sodium (DSS) and oxazolone (Oxa). Cytokine production was evaluated by mRNA quantification in colonic tissue and ELISA on supernatants of mesenteric lymph node cells.ResultsPrevalence of Hp2 was higher in CD and UC than in controls. In the confirmatory cohorts, Hp2 was over-transmitted to the affected offspring. Serum Hp concentrations were higher in individuals with genotypes Hp11 and Hp21 than in those with Hp22 (1.38 vs 0.89 g/l). DSS- and Oxa-induced colitis were more severe in Hp-deficient mice than in control mice and accompanied by higher concentrations (although not statistically significantly different) of tissue mRNA for cytokines. Interleukin-17 production was significantly higher in the presence of Hp-deficient serum compared with wild-type serum.ConclusionsThe Hp gene may play a role in susceptibility to inflammatory bowel disease. Its implication in other immune diseases underscores the common pathways between these diseases. Experimental models of colitis showed that Hp has a protective role in inflammatory colitis, most likely by inhibiting the production of Th1 and Th17 cytokines. [less ▲]

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See detailMucosal gene expression profiling differentiates early from late ileal Crohn's disease
Arijs, I; Van Lommel, L; De Hertogh, G et al

in Acta Gastro-Enterologica Belgica (2011)

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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 detailIntestinal mucosal expression of matrix metalloproteinase and ADAM genes in patients with inflammatory bowel disease and the impact of infliximab therapy
Arijs, Ingrid; Quintens, R.; Lemaire, K. et al

in Gastroenterology (2010), 138(5), 677

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See detailColonic mucosal expression of barrier genes in patients with inflammatory bowel disease before and after first infliximab treatmen
Arijs, I.; Van Lommel, L.; Van Steen, Kristel ULg et al

in Acta Gastro-Enterologica Belgica (2009)

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See detailMucosal gene signatures to predict response to infliximab in patients with ulcerative colitis
Arijs, I.; Li, K.; Toedter, G. et al

in Gut (2009), 58(12), 1612-9

BACKGROUND AND AIMS: Infliximab is an effective treatment for ulcerative colitis with over 60% of patients responding to treatment and up to 30% reaching remission. The mechanism of resistance to anti ... [more ▼]

BACKGROUND AND AIMS: Infliximab is an effective treatment for ulcerative colitis with over 60% of patients responding to treatment and up to 30% reaching remission. The mechanism of resistance to anti-tumour necrosis factor alpha (anti-TNFalpha) is unknown. This study used colonic mucosal gene expression to provide a predictive response signature for infliximab treatment in ulcerative colitis. METHODS: Two cohorts of patients who received their first treatment with infliximab for refractory ulcerative colitis were studied. Response to infliximab was defined as endoscopic and histological healing. Total RNA from pre-treatment colonic mucosal biopsies was analysed with Affymetrix Human Genome U133 Plus 2.0 Arrays. Quantitative RT-PCR was used to confirm microarray data. RESULTS: For predicting response to infliximab treatment, pre-treatment colonic mucosal expression profiles were compared for responders and non-responders. Comparative analysis identified 179 differentially expressed probe sets in cohort A and 361 in cohort B with an overlap of 74 probe sets, representing 53 known genes, between both analyses. Comparative analysis of both cohorts combined, yielded 212 differentially expressed probe sets. The top five differentially expressed genes in a combined analysis of both cohorts were osteoprotegerin, stanniocalcin-1, prostaglandin-endoperoxide synthase 2, interleukin 13 receptor alpha 2 and interleukin 11. All proteins encoded by these genes are involved in the adaptive immune response. These markers separated responders from non-responders with 95% sensitivity and 85% specificity. CONCLUSION: Gene array studies of ulcerative colitis mucosal biopsies identified predictive panels of genes for (non-)response to infliximab. Further study of the pathways involved should allow a better understanding of the mechanisms of resistance to infliximab therapy in ulcerative colitis. ClinicalTrials.gov number, NCT00639821. [less ▲]

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See detailThe impact of infliximab therapy on colonic mucosal expression of barrier genes in patients with inflammatory bowel disease
Arijs, I.; Quintens, R.; Van Lommel, L. et al

in Gastroenterology (2009), 136

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See detailColonic mucosal expression of barrier genes in patients with inflammatory bowel disease before and after first infliximab treatment.
Arijs, I.; Van Lommel, L.; Van Steen, Kristel ULg et al

in Journal of Crohn’s and Colitis [=JCC] (2009), 3(1), 3

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See detailTECK and MADCAM-1 mucosal expression in active IBD: the effect of infliximab therapy
Arijs, I.; Van Lommel, L.; Van Steen, Kristel ULg et al

in Gastroenterology (2009), 136

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See detailThe impact of infliximab therapy on colonic mucosal expression of barrier genes in patients with inflammatory bowel disease.
Arijs, I.; Quintens, R.; Van Lommel, L. et al

in Acta Gastro-Enterologica Belgica (2009)

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See detailMucosal Gene Expression of Antimicrobial Peptides in Inflammatory Bowel Disease Before and After First Infliximab Treatment
Arijs, I.; De Hertogh, G.; Lemaire, K. et al

in PLoS ONE (2009), 4(11), 7984

Background: Antimicrobial peptides (AMPs) protect the host intestinal mucosa against microorganisms. Abnormal expression of defensins was shown in inflammatory bowel disease (IBD), but it is not clear ... [more ▼]

Background: Antimicrobial peptides (AMPs) protect the host intestinal mucosa against microorganisms. Abnormal expression of defensins was shown in inflammatory bowel disease (IBD), but it is not clear whether this is a primary defect. We investigated the impact of anti-inflammatory therapy with infliximab on the mucosal gene expression of AMPs in IBD. Methodology/Principal Findings: Mucosal gene expression of 81 AMPs was assessed in 61 IBD patients before and 4-6 weeks after their first infliximab infusion and in 12 control patients, using Affymetrix arrays. Quantitative real-time reverse-transcription PCR and immunohistochemistry were used to confirm microarray data. The dysregulation of many AMPs in colonic IBD in comparison with control colons was widely restored by infliximab therapy, and only DEFB1 expression remained significantly decreased after therapy in the colonic mucosa of IBD responders to infliximab. In ileal Crohn's disease (CD), expression of two neuropeptides with antimicrobial activity, PYY and CHGB, was significantly decreased before therapy compared to control ileums, and ileal PYY expression remained significantly decreased after therapy in CD responders. Expression of the downregulated AMPs before and after treatment (DEFB1 and PYY) correlated with villin 1 expression, a gut epithelial cell marker, indicating that the decrease is a consequence of epithelial damage. Conclusions/Significance: Our study shows that the dysregulation of AMPs in IBD mucosa is the consequence of inflammation, but may be responsible for perpetuation of inflammation due to ineffective clearance of microorganisms. [less ▲]

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See detailMucosal gene signatures to predict response to infliximab in patients with inflammatory bowel disease
Arijs, I.; Van Lommel, L.; Van Steen, Kristel ULg et al

in Acta Gastro-Enterologica Belgica (2008)

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See detailGene expression of antimicrobial peptides in colonic mucosa of patients with inflammatory bowel disease before and after first infliximab treatment.
Arijs, I.; Lemaire, K.; Quintens, R. et al

in Gut (2008), 57(Suppl II), 102-103

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See detailLong-term outcome after infliximab for refractory ulcerative colitis
Ferrante, M.; Vermeire, S.; Fidder, H. et al

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 ▲]

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See detailMucosal gene signatures to predict response to infliximab in patients with inflammatory bowel disease
Arijs, I.; Van Lommel, L.; Van Steen, Kristel ULg et al

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

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See detailMucosal gene signatures to predict response to infliximab in patients with inflammatory bowel disease.
Arijs, I.; Van Lommel, L.; Van Steen, Kristel ULg et al

in Gastroenterology (2008), 134

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See detailEffect of infliximab treatment on colonic mucosal gene expression profiles in patients with inflammatory bowel disease
Arijs, I.; Quintens, R.; Van Lommel, L. et al

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

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See detailMicroarray study of mucosal antimicrobial peptides in patients with inflammatory bowel disease before and after infliximab treatment.
Arijs, I.; Van Lommel, L.; Van Steen, Kristel ULg et al

in Journal of Crohn’s and Colitis [=JCC] (2008), 2(1), 60

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