E Louis

Centre Hospitalier Universitaire de Liège, Luik, Walloon Region, Belgium

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Publications (172)532.61 Total impact

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    ABSTRACT: Background/Purpose: Immune-mediated inflammatory disorders (IMIDs) share many genetic risk factors. Pleiotropy may exist at different levels and most of the underlying mechanisms are still to be uncovered. GWAS have identified hundreds of risk loci for IMIDs but causative genes have been identified in only a handful of cases. Recent fine-mapping efforts indicate that only a minority of risk variants are coding. This suggests that most risk variants will be regulatory hence affecting disease risk via eQTL effects. Methods: To aid in the identification of causative genes for IMIDs, we generated transcriptome information (HT12 arrays) for six blood cell types (CD4, CD8, CD19, CD14, CD15 and platelets) and intestinal biopsies at three anatomical locations (ileum, colon, rectum) for 350 healthy Caucasians. The same individuals were genotyped with SNP arrays interrogating > 700K variants, augmented by imputation from the 1KG project. To detect cis-eQTL we tested variants within 0.5 megabase windows centered on the tested probe. The nominal p-value of the best SNP within a cis-window was Sidak-corrected for the window-specific number of independent tests. The corresponding best, Sidak-corrected p-values for each probe were jointly used to estimate their respective false discovery rate.To identify likely causative genes in GWAS identified risk loci variants and also better understand pleiotropic effects, we (i) developed a method that quantifies the correlation between “disease association pattern” (DAP) and “eQTL association pattern” (EAP) and provides an empirical estimate of its significance, and (ii) evaluated the effect of fitting known risk variants as covariates in the eQTL analysis following Nica et al. (2010). We applied both approaches to celiac disease (CE) and rheumatoid arthritis (RA) and the second one to type one diabetes (T1D), multiple sclerosis (MS), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS) and psoriasis (PSO). Results: We detected > 16000 significant cis-eQTL, with a degree of sharing between cell types ranging from 38 to 90% highlighting the utility of our multi-tissue panel. GWAS variants were drivers of ciseQTL effects across the different tissues in 399 tests (23.6%), mostly in CD4 cells, and pinpointing 64 new gene-disease associations (3.7%). The number of shared loci and shared eQTL were highly correlated (rho=0.66).RA and SLE showed the highest degree of sharing. Conclusions: We identified new potential candidate genes for IMIDs and characterized pleiotropic effects through ciseQTL mapping in GWAS loci. These findings could shed a light on IMIDs pathogenesis and co-occurrence. Latest results will be presented.
    cold spring harbor laboratory THE BIOLOGY OF GENOMES; 05/2015
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    ABSTRACT: The therapeutic armamentarium in Crohn's disease includes mesalazine, steroids (including topical drugs), anti-metabolites (purines, methotrexate), anti-TNFα antibodies and, more recently, selective inhibitors of lymphocytes homing (vedolizumab). The efficacy of these drugs has been shown in pivotal phase 3 placebo-controlled trials and meta-analyses. However, the use of these drugs in routine practice still remains ill-defined. Those are rather the cohort studies, natural history data and therapeutic strategy trials that help the clinician to determine, for each individual patient, the treatment leading to an optimal benefit/risk profile, aiming at moving from evidence-based medicine towards personalized medicine.
    Revue médicale de Liège 05/2015; 70(5-6):316-20.
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    ABSTRACT: Background We aimed to investigate the 163 known loci and top SNP associated with inflammatory Bowel Disease (IBD) in a non- Caucasian Moroccan IBD cohort. Methods We genotyped 549 non- Caucasian Moroccan individuals with 285 IBD patients (211 Crohn's disease (CD), 63 Ulcerative colitis (UC) and 11 Indeterminate colitis (IC)) and 264 controls on custom designed Immunochips from ILLUMINA®. We considered the 163 loci and top SNPs associated with IBD in Caucasian individuals and negative controls matched for the minor allele frequencies (MAF). After quality controls, association analysis was done using PLINK and population stratification was corrected using the first five principal components as covariates. Simulation tests with random groups of SNP (outside the 163 loci and matched for MAF) and regions (outside the 163 IBD loci and matched for the number of independent tests) were used to test the significance of the results. Results We identified 10 regions significantly associated with IBD and UC (Table1). “Table 1: ten top SNP/loci significantly associated with IBD and UC” Surprisingly, none of NOD2 variants were found to be associated with IBD moroccan population. Increasing the sample size of the used cohort will definitively help to detect more IBD loci/SNPs associated with Moroccan IBD. Conclusion This is the first genetic study conducted in a large population of Moroccan IBD patients. Ten loci/top SNP were significantly associated with IBD and UC. Interestingly, none of the NOD2 variants were found to be associated to CD/UC and Moroccan IBD.
    ECCO 2015; 02/2015
  • Acta gastro-enterologica Belgica 01/2015; 78(1):26-9. · 0.58 Impact Factor
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    ABSTRACT: Lifetime prevalence of inflammatory bowel disease (IBD) is reaching an alarming rate of >1/400 in industrialized societies. Improved understanding of disease pathogenesis is essential to develop more effective preventive, diagnostic and therapeutic measures. Genome-wide association studies (GWAS) have identified ~ 160 risk loci contributing to inherited predisposition to IBD, leading to the identification of new perturbed pathways and potential drug targets. Nevertheless, causative genes and variants remain unknown for the vast majority of risk loci. GWAS loci are likely to be regulatory and therefore alter expression levels of other genes. We hypothesize that if an IBD associated SNP is an expression quantitative loci (eQTL)-the " disease-association pattern " (DAP) should mirror the " eQTL association pattern " (EAP) of the causative gene if looking in the right target tissue(s). With this premise, our project aims to detect causative genes implicated in IBD's susceptibility through the evaluation of trans-eQTLs within GWAS loci. To this purpose, nine blood cell types and ileal, colonic and rectal biopsies have been collected for 330 healthy individuals of Northern European descent. All individuals have been genotyped with the OmniExpress Illumina array interrogating > 700K genetic variants. Transcriptome analysis has been conducted for all individuals and all cell/tissue types using Illumina HT12 arrays interrogating > 47,000 transcripts. Genotype and transcriptome data have undergone rigorous quality control. Transcriptome data have been pretreated variance stabilizing transformation, QQ normalization and correction for random and fixed effects in each cell type. Only expression probes mapped against Refseq have been considered. Genomic positions have been recovered and probes mapping to more than one genomic position (taking into account splice junctions with Tophat software) with a 96% identity have been discarded. Trans-eQTL mapping will be conducted on a SNP-by-SNP basis using linear regression (additive model) with PLINK software. In order to circumvent genome wide multiple testing penalty, we will test for a given SNP in the genome, any evidence for an excess of low p-values when testing its effect on the expression of genes located on other chromosomes or far away on the same chromosome. Confirmation of putative multigene transregulators will afterwards be performed by RNAseq experiments. We will then quantify the resemblance between DAP in the 160 GWAS-identified risk loci (raw data from IIBDGC plus imputed data) and " multigene trans-EAP " with Spearman's rank correlation. We will also evaluate the biological relevance of this list by performing a network analysis after adding the identified trans targets to the list of previously identified positional candidate genes (mapping to GWAS-identified IBD risk loci). Finally, as a the ultimate proof of causality, the selected genes will be resequenced in 3,000 IBD cases and 3,000 controls, using 600 DNA pools of 10 individuals with Illumina Truseq Amplicon. With this strategy, we expect to detect new causative variants that may constitute new drug targets for IBD. Latest results will be presented.
    BeMGI, Auditoire Léon Fredericq GIGA building B34, Level 5 University of Liège Avenue de l’Hopital 1 4000 Liège (Sart Tilman), Belgium; 04/2014
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    ABSTRACT: Our goals were to assess the prevalence of biological and tissue remission in routine practice in Crohn's disease, and to evaluate the correlation between biological or tissue remission and clinical or demographic characteristics as well as their impact on disease outcome. We performed a retrospective monocenter study. Biological remission was defined by a CRP < 5 mg/I. Tissue remission was defined by the absence of ulcer at endoscopy and/or absence of signs of acute inflammation at MRI. Association with demographic, clinical and laboratory markers was studied by logistic regression models and rates of relapses, hospitalizations and surgeries were compared using the logrank test. Among the 263 patients included, 147 were in clinical remission; 102/147 (69%) were in biological remission. Fifty-six patients also had morphological evaluation: 37 (66%) were in tissue remission. Biological remission was associated with older age, higher hemoglobin and lower BMI. Tissue remission was associated with older age, lower platelets count, absence of previous surgery, and the use of immunosuppressant. Time-to-relapse was significantly longer in patients with biological remission and in patients with tissue remission as compared to patients without biological or tissue remission. Among the patients in clinical remission seen as outpatients, two thirds were either in biological and/or tissue remission. Biological and/or tissue remission was associated with a better outcome than clinical remission alone.
    Acta gastro-enterologica Belgica 03/2014; 77(1):41-6. · 0.58 Impact Factor
  • J Tack · E Louis · V Persy · D Urbain
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    ABSTRACT: Acid peptic diseases such as peptic ulcer and gastrointestinal reflux disease have a high prevalence; they can have an important impact on the patient's quality of life and generate a considerable health care cost. Proton pump inhibitors are the most potent pharmacological inhibitors of gastric acid secretion currently available and are the mainstay medical therapy for acid peptic diseases. This review provides primary care clinicians with best practice guidelines for optimal use of these drugs.
    Revue médicale de Liège 03/2014; 69(3):139-45.
  • C. Pirard · E. Louis · C. Reenaers
    Journal of Crohn s and Colitis 02/2014; 8:S137-S138. DOI:10.1016/S1873-9946(14)60302-0 · 3.56 Impact Factor
  • Journal of Crohn s and Colitis 02/2014; 8:S274. DOI:10.1016/S1873-9946(14)60615-2 · 3.56 Impact Factor
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    ABSTRACT: Background and aims In Crohn's disease, correlation between clinical assessment and disease activity at tissue level is weak. Our aim was to evaluate the value of serum calprotectin as a biomarker for Crohn's disease. Methods The STORI trial patients (n = 115) were studied at baseline, in clinical remission before infliximab withdrawal, or at the time of relapse after infliximab withdrawal. Forty healthy controls were also studied. Serum calprotectin level was measured by ELISA. Data were analyzed through correlation analyses, Kaplan Meier curves and Cox model, using available Crohn's Disease Activity Index (CDAI), Crohn's Disease Endoscopic Index of Severity (CDEIS), fecal calprotectin and C-reactive protein levels (hsCRP). Results Median serum calprotectin was 8892 ng/mL (range: 410–125,000 ng/mL) in Crohn disease patients as compared with 1318 ng/mL (range: 215.8–3770 ng/mL) in controls (P < 0.0001). Serum calprotectin was significantly higher for active disease (median = 19,584 ng/mL) than for inactive disease (median = 8353 ng/mL) (P < 0.0001). Serum calprotectin correlated with hsCRP (r = 0.4092, P < 0.0001) and CDAI (r = 0.4442, P < 0.0001), but not with CDEIS, on the contrary to fecal calprotectin (r = 0.6458, 0.5515, 0.2577 with P < 0.0001, P < 0.0001, P = 0.019 respectively). In multivariate analysis, serum calprotectin used as a discrete variable (threshold: 5675 ng/ml), appeared complementary to hsCRP (> 5 mg/l) and fecal calprotectin (> 250 μg/g) to predict relapse after infliximab withdrawal (P = 0.0173, 0.0024 and 0.0002; HR: 3.191, 3.561 and 4.120). Conclusions As a CD biomarker, serum calprotectin has a similar profile as hsCRP. It is also complementary to fecal calprotectin and hsCRP for prediction of relapse after infliximab withdrawal.
    Journal of Crohn s and Colitis 12/2013; 7(12):e678–e683. DOI:10.1016/j.crohns.2013.06.008 · 3.56 Impact Factor
  • J Tack · E Louis · V Persy · D Urbain
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    ABSTRACT: Heartburn, reflux and epigastric pain are frequently encountered symptoms in primary care medicine. Acid peptic diseases such as peptic ulcer and gastrointestinal reflux disease have a high prevalence, can have important impact on patient quality of life and represent a considerable health care cost. Proton pump inhibitors (PPIs) are the most potent pharmacological inhibitors of gastric acid secretion currently available and are the mainstay medical therapy for acid peptic diseases. This review summarizes current evidence on treatment of acid-peptic diseases with proton pump inhibitors and provides primary care clinicians with best practice guidelines for optimal use of these drugs.
    Acta gastro-enterologica Belgica 12/2013; 76(4):393-402. · 0.58 Impact Factor
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    ABSTRACT: The thyrogastric autoimmune syndrome (TAS) was described in patients in whom the serum cross-reacted both with gastric parietal cells antigens and thyroid antigens. We report two cases illustrating the spectrum of pathogical features of TAS. The first case associates Hashimoto's thyroiditis and anemia perniciosa,and develops a gastric neuroendocrine tumor during follow up. The second case presents with a Graves' disease and an autoimmune reversible gastritis, secondary to Helicobacter pylori. Whereas type III autoimmune polyendocrinopathy is rare, TAS is frequent in our experience. Some 13% (32/240) of patients that we have prospectively followed affected with thyroiditis have also autoimmune gastritis. Helicobacter pylori is clearly implicated in 16% of autoimmune gastritis cases. Infection, malabsorption and gastritis are potentially reversible after bacterial eradication treatment. In the other 84% of gastritis patients, no histological or serological proof of Helicobacter pylori is found. Gastric autoimmunity is then irreversible, leading to gastric severe atrophy, hypochlorhydria and hypergastrinemia. Hypergastrinemia stimulates enterochromaffin cell hyperplasia, possibly progressing to neuroendocrine tumors. We propose a diagnostic approach to improve the characterization of TAS. We review the literature on the subject and discuss some interesting animal models of infectious gastric autoimmunity.
    Revue médicale de Liège 11/2013; 68(11):579-84.
  • Annales d Endocrinologie 09/2013; 74(4):294. DOI:10.1016/j.ando.2013.07.171 · 0.66 Impact Factor
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    J. M. Benitez · E. Louis
    Alimentary Pharmacology & Therapeutics 09/2013; 38(5). DOI:10.1111/apt.12416 · 5.48 Impact Factor
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    ABSTRACT: Abstract AIM: A Belgian registry for pediatric Crohn's disease, BELCRO, was created. This first report aims at describing disease presentation and phenotype and determining associations between variables at diagnosis and registration in the database. METHODS: Through a collaborative network, children with previously established Crohn's disease and newly diagnosed children and adolescents (under 18y of age) were recruited over a 2year period. Data were collected by 23 centers and entered in a database. Statistical association tests analyzed relationships between variables of interest at diagnosis. RESULTS: Two hundred fifty-five patients were included. Median age at diagnosis was 12.5y (range: 1.6-18y); median duration of symptoms prior to diagnosis was 3m (range: 1-12m). Neonatal history and previous medical history did not influence disease onset nor disease behavior. Fifty three % of these patients presented with a BMI z-score<-1. CRP was an independent predictor of disease severity. Steroids were widely used as initial treatment in moderate to severe and extensive disease. Over time, immunomodulators and biological were prescribed more frequently, reflecting a lower prescription rate for steroids and 5-ASA. A positive family history was the sole significant determinant for earlier use of immunosuppression. CONCLUSION: In Belgium, the median age of children presenting with Crohn's disease is 12.5y. Faltering growth, extensive disease and upper GI involvement are frequent. CRP is an independent predictive factor of disease activity. A positive family history appears to be the main determinant for initial treatment choice.
    Journal of Crohn s and Colitis 04/2013; 7(11). DOI:10.1016/j.crohns.2013.04.016 · 3.56 Impact Factor
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    Alimentary Pharmacology & Therapeutics 04/2013; 37(7):752-3. DOI:10.1111/apt.12245 · 4.55 Impact Factor
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    Journal of Crohn's and Colitis; 02/2013
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    ABSTRACT: Biologicals have become an important component in the treatment of Crohn's disease in children. Their increased and long term use raises safety concerns. We describe safety and cost of infliximab in Belgian pediatric Crohn's disease patients. All patients on infliximab as part of the present or past treatment for Crohn's Disease until January 1st 2011 were selected from an existing database. Information on disease phenotype, medication and adverse events were extracted. Adverse events occurred in 25.9% of patients exposed to infliximab of which 29.6% were severe. In total 31.7% of patients stopped infliximab therapy. The main reasons for discontinuation were adverse events in 45.4% and loss of response in 30.3%. No malignancies or lethal complications occurred over this 241 patient year observation period. Immunomodulators were concomitant medication in 75% of patients and were discontinued subsequently in 38.4% of them. The cost of infliximab infusions per treated patient per year in the Belgian health care setting is approximately 9 474 euro, including only medication and hospital related costs. Even though infliximab is relatively safe in pediatric CD on the short term, close follow-up and an increased awareness of the possible adverse reactions is highly recommended. Adverse reactions appeared in 25.9% of all patients and were the main reason for discontinuation. Treatment cost has to be balanced against efficacy and modifications in disease course. In the Belgian health care system, the medication is available to all patients with moderate to severe CD.
    Acta gastro-enterologica Belgica 12/2012; 75(4):425-31. DOI:10.1016/S1873-9946(12)60266-9 · 0.58 Impact Factor
  • F Desselle · G Verset · M Polus · E Louis · D Van Daele
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    ABSTRACT: Microsatellite instability (MSI) phenotype occurs in approximately 15 to 24% of colorectal cancer (CRC) patients and may be sporadic or hereditary. It reflects a mutator phenotype in the tumor due to a lack of mismatch repair system. MSI is indeed one of the characteristics of CRCs occurring in Lynch syndrome and some sporadic cases. CRCs with MSI have a better prognosis than CRCs with microsatellite stability (MSS). This is explained partly by a more important anti-tumor immune response and by apoptosis of tumor cells in which mutations accumulate. However, in some retrospective studies, microsatellite instability in stage II CRCs was associated with no benefit to or even a deleterious effect of 5-FU alone based adjuvant therapy. Nevertheless, results obtained in stage III CRCs with FOLFOX type adjuvant chemotherapy remain favorable in retrospective studies.
    Revue médicale de Liège 12/2012; 67(12):638-43.
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    ABSTRACT: There is clear benefit from combination therapy with infliximab and immunosuppressive drugs (IS), but few data are available for adalimumab (ADA). To assess the efficacy of ADA monotherapy and ADA+IS for induction and maintenance therapy in Crohn's disease. Retrospective study of patients with Crohn's disease treated with ADA in Oxford, UK or Liège, Belgium. Treatment periods were divided into 6-month semesters. A combination therapy semester was defined as ADA+IS for at least 3 months; successful induction meant clinical response; a semester with flare as ADA dose escalation, starting steroids, perianal complication, or surgery; and ADA failure as ADA withdrawal for secondary loss of response or intolerance. Semesters with and without flares were compared through univariate and multivariate analysis. Successful induction was achieved in 171/207 (83%) patients, with no significant difference between ADA+IS and ADA monotherapy (85% vs. 82%, P = 0.50). Five hundred and sixty-two semesters in 181 patients were included for maintenance analysis. ADA+IS was not associated with fewer semesters with flare (34% vs. 35%, P = 0.96), or with ADA failure (6% vs. 8%, P = 0.43). Nevertheless, combination therapy in the first semester was associated with a lower risk of ADA failure (5% vs. 10%, P = 0.04, OR = 0.48) and combination therapy beyond 6 months was associated with fewer semesters with flares (14% vs. 36%, P = 0.02, OR = 0.31). There may be a benefit from adalimumab+immunosuppressive drugs combination therapy during the first semester of initiating adalimumab, with a slight decrease in adalimumab failure and lower need for adalimumab dosage escalation.
    Alimentary Pharmacology & Therapeutics 10/2012; 36(11-12). DOI:10.1111/apt.12076 · 4.55 Impact Factor

Publication Stats

3k Citations
532.61 Total Impact Points

Institutions

  • 1994–2013
    • Centre Hospitalier Universitaire de Liège
      • Department of Pathology
      Luik, Walloon Region, Belgium
  • 1989–2013
    • University of Liège
      • • Department of Gastroenterology
      • • Department of Pathology
      • • Department of Pneumology
      Luik, Walloon, Belgium
  • 2004–2005
    • Free University of Brussels
      • Department of Gastroenterology
      Bruxelles, Brussels Capital Region, Belgium
  • 1998
    • University of Leuven
      Louvain, Flemish, Belgium
    • University of Southampton
      Southampton, England, United Kingdom
  • 1995
    • Province de Liège
      Luik, Wallonia, Belgium