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1. On the Geometrically Exact Low Order Modelling of a Flexible Beam: Formulation and Numerical Tests

Author

Howcroft, C., Cook, R. G., Neild, S. A., Lowenberg, M. H., Cooper, J. E., and Coetzee, E. B.

Subjects
Physics - Classical Physics, Mathematics - Classical Analysis and ODEs
Abstract

This paper proposes a low order geometrically exact flexible beam formulation based on the utilisation of generic beam shape functions to approximate distributed kinematic properties of the deformed structure. The proposed nonlinear beam shapes approach is in contrast to the majority of geometrically nonlinear treatments in the literature in which element based --- and hence high order --- discretisations are adopted. The kinematic quantities approximated specifically pertain to shear and extensional gradients as well as local orientation parameters based on an arbitrary set of globally referenced attitude parameters. In developing the dynamic equations of motion, an Euler angle parameterisation is selected as it is found to yield fast computational performance. The resulting dynamic formulation is closed using an example shape function set satisfying the single generic kinematic constraint. The formulation is demonstrated via its application to the modelling of a series of static and dynamic test cases of both simple and non-prismatic structures; the simulated results are verified using MSC Nastran and an element-based intrinsic beam formulation. Through these examples it is shown that the nonlinear beam shapes approach is able to accurately capture the beam behaviour with a very minimal number of system states.

Published
2018
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6. Persistence of seroconversion at 6 months following primary immunisation in patients with immune-mediated inflammatory diseases

Author

Wieske, L., Stalman, E.W., Dam, P.J.K. van, Kummer, L.Y., Steenhuis, M., Kempen, Z.L.E. van, Killestein, J., Volkers, A.G., Tas, S.W., Boekel, L., Wolbink, G., Kooi, A. van der, Raaphorst, J., Lowenberg, M., Takkenberg, B., D'Haens, G.R.A.M., Spuls, P.I., Bekkenk, M.W., Musters, A.H., Post, N.F., Bosma, A.L., Hilhorst, M.L., Vegting, Y., Bemelman, F.J., Voskuyl, A., Broens, B., Sanchez, A.P., Els, C.A.C.M. van, Wit, J. de, Rutgers, A., Leeuw, K. de, Horvath, B., Verschuuren, J.J.G.M., Ruiter, A.M., Ouwerkerk, L. van, Woude, D. van der, Allaart, C.F., Teng, Y.K.O., Paassen, P. van, Busch, M.H., Jallah, P.B.P., Brusse, E., Doorn, P.A. van, Baars, A.E., Hijnen, D., Schreurs, C.R.G., Pol, W.L. van der, Goedee, H.S., Keijzer, S., Keijser, J., Cristianawati, O., Brinke, A. ten, Verstegen, N.J.M., Zwinderman, K.A.H., Ham, S.M. van, Kuijpers, T.W., Rispens, T., Eftimov, F., T2B Immunity SARS CoV 2 Study Grp, Interne Geneeskunde, MUMC+: MA Nefrologie (9), MUMC+: MA Klinische Immunologie (9), RS: Carim - B02 Vascular aspects thrombosis and Haemostasis, Neurology, Amsterdam Neuroscience - Neuroinfection & -inflammation, AII - Inflammatory diseases, Rheumatology, Dermatology, Nephrology, and AII - Infectious diseases

Subjects
Rheumatology, SDG 3 - Good Health and Well-being, Immunology, Vaccination, Immunology and Allergy, Tumor Necrosis Factor Inhibitors, Covid-19, General Biochemistry, Genetics and Molecular Biology, Autoimmune Diseases
Abstract

Patients with immune-mediated inflammatory diseases (IMIDs) may have impaired initial humoral responses after SARS-CoV-2 vaccination depending on the type of immunosuppression (ISP) used.1 It is largely unknown how antibody titres develop over time and whether it is needed to adjust timing of booster campaigns for patients with IMID.

Published
2023

8. Primary SARS-CoV-2 infection in patients with immune-mediated inflammatory diseases

Author

Dam, K.P.J. van, Volkers, A.G., Wieske, L., Stalman, E.W., Kummer, L.Y.L., Kempen, Z.L.E. van, Killestein, J., Tas, S.W., Boekel, L., Wolbink, G.J., Kooi, A.J. van der, Raaphorst, J., Takkenberg, R.B., D'Haens, G.R.A.M.I., Spuls, P.W., Bekkenk, M.H., Musters, A.F., Post, N.L., Bosma, A.L., Hilhorst, M., Vegting, Y.J., Bemelman, F.E., Voskuyl, A., Broens, B., Sanchez, A.P., Els, C.A.C.M. van, Wit, J. de, Rutgers, A., Leeuw, K. de, Horvath, B., Verschuuren, J.J.G.M.M., Ruiter, A.M., Ouwerkerk, L. van, Woude, D. van der, Allaart, R.C.F., Teng, Y.K.O., Paassen, P.H. van, Busch, M.H., Jallah, P.B.P., Brusse, E., Doorn, P.A. van, Baars, A.E., Hijnen, D.J., Schreurs, C.R.G., Pol, W.L. van der, Goedee, H.S., Steenhuis, M., Keijzer, S., Keijser, J.B.D., Cristianawati, O., Brinke, A. ten, Verstegen, N.J.M., Ham, S.M. van, Rispens, T.W., Kuijpers, T., Lowenberg, M., Eftimov, F., and TB2 Immunity Sars-Cov-2 Study Grp

Subjects
Immune-mediated inflammatory diseases, SARS-CoV-2, Autoimmune disease, TNF, Immunity, Disease activity, Covid-19, Immunosuppression, Antibodies, Flare
Abstract

Background: Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressants (ISPs) may have impaired long-term humoral immune responses and increased disease activity after SARS-CoV-2 infection. We aimed to investigate long-term humoral immune responses against SARS-CoV-2 and increased disease activity after a primary SARS-CoV-2 infection in unvaccinated IMID patients on ISPs. Methods: IMID patients on active treatment with ISPs and controls (i.e. IMID patients not on ISP and healthy controls) with a confirmed SARS-CoV-2 infection before first vaccination were included from an ongoing prospective cohort study (T2B! study). Clinical data on infections and increased disease activity were registered using electronic surveys and health records. A serum sample was collected before first vaccination to measure SARS-CoV-2 anti-receptor-binding domain (RBD) antibodies. Results: In total, 193 IMID patients on ISP and 113 controls were included. Serum samples from 185 participants were available, with a median time of 173 days between infection and sample collection. The rate of seropositive IMID patients on ISPs was 78% compared to 100% in controls (p < 0.001). Seropositivity rates were lowest in patients on anti-CD20 (40.0%) and anti-tumor necrosis factor (TNF) agents (60.5%), as compared to other ISPs (p < 0.001 and p < 0.001, respectively). Increased disease activity after infection was reported by 68 of 260 patients (26.2%; 95% CI 21.2-31.8%), leading to ISP intensification in 6 out of these 68 patients (8.8%). Conclusion: IMID patients using ISPs showed reduced long-term humoral immune responses after primary SARS-CoV-2 infection, which was mainly attributed to treatment with anti-CD20 and anti-TNF agents. Increased disease activity after SARS-CoV-2 infection was reported commonly, but was mostly mild.

Published
2023

12. Safety and efficacy of combining biologics or small molecules for inflammatory bowel disease or immune-mediated inflammatory diseases

Author

Goessens, L., Colombel, J. -F., Outtier, A., Ferrante, M., Sabino, J., Judge, C., Saeidi, R., Rabbitt, L., Armuzzi, A., Domenech, E., Michalopoulos, G., Cremer, A., Garcia-Alonso, F. J., Molnar, T., Karmiris, K., Gecse, K., Van Oostrom, J., Lowenberg, M., Farkas, K., Atreya, R., Ribaldone, D. G., Selinger, C., Hoentjen, F., Bihin, B., Sebastian, S., Rahier, J. -F., Baert, F., Horin, S. B., Bossuyt, P., Mas, E. B., Buckley, M., Byron, C., Coe, C., Doherty, G. A., Dragoni, G., Fernandes, S., Gaya, D. P., Gleeson, S., Keogh, A., Levine, A., Ortega, T. L., Lobo, A. J., Macken, E., Mccarthy, J., Noor, N., O'Toole, A., Posen, A., Privitera, G., Pugliese, D., Raine, T., Reenaers, C., Resal, T., Scarcelli, A., Slattery, E., Strubbe, B., Sugrue, K., Groen, M. T., Vicente, G. T., Truyens, M., Viola, A., Yanai, H., Zulquernain, S. A., Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Graduate School, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (MGD) Service de gastro-entérologie, UCL - SSS/IREC/MONT - Pôle Mont Godinne, and UCL - (MGD) Unité de support scientifique

Subjects
Adult, Male, safety, medicine.medical_specialty, Combination therapy, Adolescent, Opportunistic infection, Inflammatory bowel disease, combination therapy, Young Adult, Interquartile range, inflammatory bowel disease, Internal medicine, Medicine, Humans, biologics, Adverse effect, Retrospective Studies, Biological Products, treatment, business.industry, immune mediated inflammatory disease, Gastroenterology, Retrospective cohort study, medicine.disease, Inflammatory Bowel Diseases, Europe, small molecules, Oncology, Immune-mediated inflammatory diseases, Original Article, Drug Therapy, Combination, Female, Skin cancer, business, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5]
Abstract

BACKGROUND AND AIMS: Few data are available regarding the combination of biologics or small molecules in inflammatory bowel disease (IBD) patients. We report safety and efficacy of such combinations through a retrospective multicentre series. METHODS: Combination therapy was defined as the concomitant use of two biologics or one biologic with a small molecule. Patient demographics, disease characteristics and types of combinations were recorded. Safety was evaluated according to the occurrence of serious infection, opportunistic infection, hospitalisation, life-threatening event, worsening of IBD or immune-mediated inflammatory diseases (IMID), cancer and death. Efficacy was evaluated as the physician global assessment of the combination and comparison of clinical/endoscopic scores of IBD/IMID activity prior and during combination. RESULTS: A total of 104 combinations were collected in 98 patients. Concomitant IMID were present in 41 patients. Reasons for starting combination therapy were active IBD (67%), active IMID or extra-intestinal manifestations (EIM) (22%), both (10%) and unclassified in 1. Median duration of combination was 8 months (interquartile range 5-16). During 122 patient-years of follow-up, 42 significant adverse events were observed, mostly related to uncontrolled IBD. There were 10 significant infections, 1 skin cancer and no death. IBD disease activity was clinically improved in 70% and IMID/EIM activity in 81% of the patients. Overall, combination was continued in 55% of the patients. CONCLUSIONS: Combination of biologics and small molecules in patients with IBD and IMID/EIM seems to be a promising therapeutic strategy but is also associated with a risk of opportunistic infections or infections leading to hospitalisation in 10%. ispartof: UNITED EUROPEAN GASTROENTEROLOGY JOURNAL vol:9 issue:10 pages:1136-1147 ispartof: location:England status: published

Published
2021

14. Breakthrough infections with the SARS-CoV-2 omicron (B.1.1.529) variant in patients with immune-mediated inflammatory diseases

Author

Stalman, E.W., Wieske, L., Dam, K.P.J. van, Kummer, L.Y., Kempen, Z.L.E. van, Killestein, J., Volkers, A.G., Tas, S.W., Boekel, L., Wolbink, G.J., Kooi, A.J. van der, Raaphorst, J., Lowenberg, M., Takkenberg, R.B., D'Haens, G.R.A.M., Spuls, P.I., Bekkenk, M.W., Musters, A.H., Post, N.F., Bosma, A.L., Hilhorst, M.L., Vegting, Y., Bemelman, F.J., Voskuyl, A.E., Broens, B., Sanchez, A.P., Els, C.A.C.M. van, Wit, J. de, Rutgers, A., Leeuw, K. de, Horvath, B., Verschuuren, J.J.G.M., Ruiter, A.M., Ouwerkerk, L. van, Woude, D. van der, Allaart, C.F., Teng, O.Y.K., Paassen, P. van, Busch, M.H., Jallah, P.B.P., Brusse, E., Doorn, P.A. van, Baars, A.E., Hijnen, D.J., Schreurs, C.R.G., Pol, W.L. van der, Goedee, H.S., Steenhuis, M., Keijzer, S., Keijser, J.B.D., Boogaard, A., Cristianawati, O., Brinke, A. ten, Verstegen, N.J.M., Zwinderman, K.A.H., Rispens, T., Ham, S.M. van, Kuijpers, T.W., Eftimov, F., T2B Immunity Against SARS Co, Neurology, Dermatology, Graduate School, Paediatrics, Gastroenterology and Hepatology, Experimental Immunology, Clinical Immunology and Rheumatology, AII - Inflammatory diseases, Landsteiner Laboratory, ANS - Neuroinfection & -inflammation, ANS - Neurodegeneration, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, APH - Methodology, APH - Quality of Care, AII - Cancer immunology, Nephrology, 01 Internal and external specialisms, ACS - Atherosclerosis & ischemic syndromes, Epidemiology and Data Science, Paediatric Infectious Diseases / Rheumatology / Immunology, ARD - Amsterdam Reproduction and Development, EURO-NMD, Translational Immunology Groningen (TRIGR), SILS Other Research (FNWI), Amsterdam Neuroscience - Neuroinfection & -inflammation, Rheumatology, Molecular cell biology and Immunology, Pediatrics, Interne Geneeskunde, MUMC+: MA Nefrologie (9), MUMC+: MA Klinische Immunologie (9), RS: Carim - B02 Vascular aspects thrombosis and Haemostasis, and MUMC+: MA Med Staf Artsass Interne Geneeskunde (9)

Subjects
COVID-19 Vaccines, SARS-CoV-2, Immunology, Vaccination, Autoimmunity, General Biochemistry, Genetics and Molecular Biology, Autoimmune Diseases, Cohort Studies, Rheumatology, SDG 3 - Good Health and Well-being, Immunology and Allergy, Humans, Prospective Studies, Covid-19, Immunosuppressive Agents
Abstract

ObjectivesTo compare the cumulative incidence and disease severity of reported SARS-CoV-2 omicron breakthrough infections between patients with immune-mediated inflammatory diseases (IMID) on immunosuppressants and controls, and to investigate determinants for breakthrough infections.MethodsData were used from an ongoing national prospective multicentre cohort study on SARS-CoV-2 vaccination responses in patients with IMID in the Netherlands (Target-to-B! (T2B!) study). Patients wih IMID on immunosuppressants and controls (patients with IMID not on immunosuppressants and healthy controls) who completed primary immunisation were included. The observation period was between 1 January 2022 and 1 April 2022, during which the SARS-CoV-2 omicron (BA.1 and BA.2 subvariant) was dominant. A SARS-CoV-2 breakthrough infection was defined as a reported positive PCR and/or antigen test at least 14 days after primary immunisation. A multivariate logistic regression model was used to investigate determinants.Results1593 patients with IMID on immunosuppressants and 579 controls were included. The cumulative incidence of breakthrough infections was 472/1593 (29.6%; 95% CI 27% to 32%) in patients with IMID on immunosuppressants and 181/579 (31.3%; 95% CI 28% to 35%) in controls (p=0.42). Three (0.5%) participants had severe disease. Seroconversion after primary immunisation (relative risk, RR 0.71; 95% CI 0.52 to 0.96), additional vaccinations (RR 0.61; 95% CI 0.49 to 0.76) and a prior SARS-CoV-2 infection (RR 0.60; 95% CI 0.48 to 0.75) were associated with decreased risk of breakthrough infection.ConclusionsThe cumulative incidence of reported SARS-CoV-2 omicron breakthrough infections was high, but similar between patients with IMID on immunosuppressants and controls, and disease severity was mostly mild. Additional vaccinations and prior SARS-CoV-2 infections may reduce the incidence of breakthrough infections.

Published
2022

18. Genetic Risk Scores Identify Genetic Aetiology of Inflammatory Bowel Disease Phenotypes

Author

Voskuil, M.D., Spekhorst, L.M., Sloot, K.W.J. van der, Jansen, B.H., Dijkstra, G., Woude, C.J. van der, Hoentjen, F., Pierik, M.J., Meulen, A.E. van der, Boer, N.K.H. de, Lowenberg, M., Oldenburg, B., Festen, E.A.M., Weersma, R.K., Parelsnoer Inst, Dutch Initiative Crohn Colitis, Translational Immunology Groningen (TRIGR), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Institute for Organ Transplantation (GIOT), Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Interne Geneeskunde, MUMC+: MA Maag Darm Lever (9), RS: NUTRIM - R2 - Liver and digestive health, Gastroenterology and hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, and Gastroenterology & Hepatology

Subjects
Male, 0301 basic medicine, Oncology, LOCI, Genome-wide association study, Disease, SUSCEPTIBILITY, Inflammatory bowel disease, 0302 clinical medicine, Crohn Disease, Risk Factors, Pleiotropy, Medicine, Digestive System Surgical Procedures, Netherlands, Gastroenterology, phenotypes, General Medicine, Middle Aged, PRIMARY SCLEROSING CHOLANGITIS, Ulcerative colitis, CROHNS-DISEASE, 030220 oncology & carcinogenesis, Cohort, Female, Symptom Assessment, SMOKING, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], Adult, medicine.medical_specialty, Cholangitis, Sclerosing, Primary sclerosing cholangitis, 03 medical and health sciences, inflammatory bowel disease, Internal medicine, Genetic variation, Genetics, Humans, Genetic Testing, GENOME-WIDE ASSOCIATION, Genetic Association Studies, business.industry, medicine.disease, digestive system diseases, Patient Care Management, 030104 developmental biology, Pharmacogenetics, DENSITY, Colitis, Ulcerative, business, Genome-Wide Association Study
Abstract

Background and Aims Inflammatory bowel disease [IBD] phenotypes are very heterogeneous between patients, and current clinical and molecular classifications do not accurately predict the course that IBD will take over time. Genetic determinants of disease phenotypes remain largely unknown but could aid drug development and allow for personalised management. We used genetic risk scores [GRS] to disentangle the genetic contributions to IBD phenotypes. Methods Clinical characteristics and imputed genome-wide genetic array data of patients with IBD were obtained from two independent cohorts [cohort A, n = 1097; cohort B, n = 2156]. Genetic risk scoring [GRS] was used to assess genetic aetiology shared across traits and IBD phenotypes. Significant GRS–phenotype (false-discovery rate [FDR] corrected p Results Crohn’s disease [CD] GRS were associated with fibrostenotic CD [R2 = 7.4%, FDR = 0.02] and ileocaecal resection [R2 = 4.1%, FDR = 1.6E-03], and this remained significant after correcting for previously identified clinical and genetic risk factors. Ulcerative colitis [UC] GRS [R2 = 7.1%, FDR = 0.02] and primary sclerosing cholangitis [PSC] GRS [R2 = 3.6%, FDR = 0.03] were associated with colonic CD, and these two associations were largely driven by genetic variation in MHC. We also observed pleiotropy between PSC genetic risk and smoking behaviour [R2 = 1.7%, FDR = 0.04]. Conclusions Patients with a higher genetic burden of CD are more likely to develop fibrostenotic disease and undergo ileocaecal resection, whereas colonic CD shares genetic aetiology with PSC and UC that is largely driven by variation in MHC. These results further our understanding of specific IBD phenotypes.

Published
2021

24. Vulvar and vaginal neoplasia in women with inflammatory bowel disease

Author

Rouvroye, M.D., Tack, G.J., Mom, C.H., Lissenberg-Witte, B.I., Pierik, M.J., Neefjes-Borst, E.A., Boer, N.K.H. de, Lowenberg, M., Bodelier, A., Verbeek, W.H., Schoon, E., Witteman, E.M., Herwaarden, M.A., Woude, C.J. van der, Lutgens, M., Kouw, E., Veek, P.J. van der, Hulst, R.W. van der, Sipkema, H., Nissen, L.H.C., Bus, P.J., Meulen, A.E. van der, Bruijne, F.H. de, Waaij, L.A. van der, Noomen, C.G., Jharap, B., Schmittgens, S., Jansen, J.M., Hoentjen, F., Lammertink, M.H.A., Houben, G.M.P., Minderhoud, I.M., Dijkstra, G., Oldenburg, B., Sikkens, M.S.G., Tuyl, S.A. van, Bodegraven, A.A. van, Dutch Workgrp IBD Vulvovaginal Neo, Academic Medical Center, Amsterdam Gastroenterology Endocrinology Metabolism, Interne Geneeskunde, MUMC+: MA Maag Darm Lever (9), RS: NUTRIM - R2 - Liver and digestive health, Anatomy and neurosciences, Gastroenterology and hepatology, Obstetrics and gynaecology, Amsterdam Reproduction & Development (AR&D), Epidemiology and Data Science, Pathology, AGEM - Digestive immunity, Other Research, AII - Inflammatory diseases, APH - Methodology, Groningen Institute for Organ Transplantation (GIOT), Translational Immunology Groningen (TRIGR), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), and Gastroenterology & Hepatology

Subjects
Inflammatory bowel disease, 0302 clinical medicine, Risk Factors, Epidemiology, EPIDEMIOLOGY, Registries, INCREASED RISK, Netherlands, Vaginal cancer, education.field_of_study, Vulvar Neoplasms, Incidence, Gastroenterology, Middle Aged, CANCER, PREVALENCE, THIOPURINES, Immunosuppressive therapy, 030220 oncology & carcinogenesis, Cohort, SURVIVAL, Female, 030211 gastroenterology & hepatology, FEMALE GENITAL-TRACT, Carcinoma in Situ, Immunosuppressive Agents, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], Adult, medicine.medical_specialty, Vaginal Neoplasms, Adolescent, Population, Malignancy, Young Adult, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Internal medicine, Journal Article, medicine, Humans, COHORT, Medical history, education, Aged, Retrospective Studies, Hepatology, business.industry, HUMAN-PAPILLOMAVIRUS, Cancer, Inflammatory Bowel Diseases, medicine.disease, TRENDS, Vulvar or vaginal malignancy, Neoplasm Recurrence, Local, business
Abstract

Immunosuppressive drugs are the cornerstone in the treatment of inflammatory bowel disease (IBD), however they are associated with an increased risk of extra-intestinal cancer. Whether the risk for female genital tract malignancies, including vulvar and vaginal cancer, is increased is less clear.Our aim was to investigate the risk of these malignancies in IBD-patients.Histopathological data of all IBD patients with a vulvar or vaginal (pre-)cancerous lesion were retrieved from the Dutch nationwide network and registry of histopathology and cytopathology from 1991 to 2015. Medical history was retrieved from patient records. Data from the Central Office for Statistics, the Dutch comprehensive cancer organization, and the IBDSL cohort were obtained to calculate the standardized, and age-adjusted incidence rates.Fifty-five patients met the inclusion criteria. A standardized incidence rate of 1.2(95% CI:0.8-1.7) for vulvar and vaginal carcinoma among adult female IBD was calculated, which did not significantly differ from the general population. The use of immunosuppressive therapy did not increase the occurrence of vulvovaginal malignancy, nor did it influence the recurrence rate. However, immunosuppressive drugs ever-users were on average 11 years younger at the time of their gynaecological diagnosis.Overall, our data do not support intensified screening for vulvar or vaginal malignancies in female IBD patients. (C) 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Published
2020

25. Real-world experience of switching from intravenous to subcutaneous vedolizumab maintenance treatment for inflammatory bowel diseases

Author

Volkers, A., Straatmijer, T., Duijvestein, M., Sales, A., Levran, A., Schaik, F. van, Maljaars, J., Gecse, K., Ponsioen, C., Grootjans, J., Hanzel, J., Tack, G., Jansen, J., Hoentjen, F., Boer, N. de, Marel, S. van der, Dijkstra, G., Oldenburg, B., Lowenberg, M., Meulen, A. van der, D'Haens, G., IBD Ctr Amsterdam, Dutch Initiative Crohn Colitis, Gastroenterology and Hepatology, Graduate School, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Tytgat Institute for Liver and Intestinal Research, Groningen Institute for Organ Transplantation (GIOT), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), Gastroenterology and hepatology, and Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
Hepatology, INDUCTION, Remission Induction, Gastroenterology, Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], Antibodies, Monoclonal, Humanized, Inflammatory Bowel Diseases, THERAPY, Treatment Outcome, Crohn Disease, Gastrointestinal Agents, Phobic Disorders, inflammatory bowel disease, REGISTRY, Humans, Colitis, Ulcerative, subcutaneous vedolizumab, Pharmacology (medical), Prospective Studies, real-world evidence, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5]
Abstract

Contains fulltext : 288020.pdf (Publisher’s version ) (Open Access) BACKGROUND: Subcutaneous (SC) vedolizumab is effective in inflammatory bowel diseases (IBD) when administered after induction with two infusions. AIM: To assess the effectiveness, safety and pharmacokinetics of a switch from intravenous (IV) to SC maintenance vedolizumab in patients with IBD METHODS: In this prospective cohort study, patients with IBD who had ≥4 months IV vedolizumab were switched to SC vedolizumab. We studied the time to discontinuation of SC vedolizumab, adverse events (AEs), changes in clinical and biochemical outcomes and vedolizumab concentrations at baseline, and weeks 12 and 24. RESULTS: We included 82 patients with Crohn's disease (CD) and 53 with ulcerative colitis (UC). Eleven (13.4%) patients with CD and five (9.4%) with UC discontinued SC vedolizumab after a median of 18 (IQR 8-22) and 6 weeks (IQR 5-10), respectively. Four patients with CD switched to a different drug due to loss of response, nine switched back to IV vedolizumab due to adverse events, and three due to needle fear. Common AEs were injection site reactions (n = 15) and headache (n = 6). Median clinical and biochemical disease activity remained stable after the switch. Median serum vedolizumab concentrations increased from 19 μg/ml at the time of the switch to 31 μg/ml 12 weeks after the switch (p

Published
2022

26. Humoral immune response after SARS-CoV-2 vaccination in patients with immune-mediated inflammatory diseases treated with immunosuppressive therapy - a Target to B! study

Author

Volkers, A., Wieske, L., van Dam, K., Steenhuis, M., Stalman, E., Kummer, L., van Kempen, Z., Killestein, J., Tas, S., Boekel, L., Wolbink, G., Takkenberg, B., Spuls, P., Bosma, A., Rutgers, B., Verschuuren, J., van Ouwerkerk, L., van der Woude, D., van Paassen, P., Busch, M., Brusse, E., Hijnen, D., ten Brinke, A., Verstegen, N., D'Haens, G., van Ham, M., Kuijpers, T., Rispens, T., Lowenberg, M., Eftimov, F., Neurology, and Dermatology

Subjects
SDG 3 - Good Health and Well-being
Published
2022

31. Ustekinumab is associated with superior effectiveness outcomes compared to vedolizumab in Crohn's disease patients with prior failure to anti-TNF treatment

Author

Biemans, V.B.C., Woude, C.J. van der, Dijkstra, G., Meulen-de Jong, A.E. van der, Lowenberg, M., Boer, N.K. de, Oldenburg, B., Srivastava, N., Jansen, J.M., Bodelier, A.G.L., West, R.L., Vries, A.C. de, Haans, J.J.L., Jong, D. de, Hoentjen, F., Pierik, M.J., Dutch Initiative Crohn Colitis ICC, Interne Geneeskunde, RS: NUTRIM - R2 - Liver and digestive health, MUMC+: MA Maag Darm Lever (9), Gastroenterology and Hepatology, AGEM - Digestive immunity, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology & Hepatology, Translational Immunology Groningen (TRIGR), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Institute for Organ Transplantation (GIOT), and Gastroenterology and hepatology

Subjects
Adult, Male, medicine.medical_specialty, MAINTENANCE THERAPY, DOSE INTENSIFICATION, Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], Antibodies, Monoclonal, Humanized, Inflammatory bowel disease, Article, Vedolizumab, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, Crohn Disease, Gastrointestinal Agents, Internal medicine, adalimumab, Ustekinumab, Adalimumab, Medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Registries, Adverse effect, Propensity Score, Netherlands, Hepatology, inflammatory-bowel-disease, business.industry, Tumor Necrosis Factor-alpha, INDUCTION, Remission Induction, Gastroenterology, Odds ratio, Middle Aged, medicine.disease, Treatment Outcome, Propensity score matching, 030211 gastroenterology & hepatology, Original Article, Female, business, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], medicine.drug
Abstract

Contains fulltext : 220027.pdf (Publisher’s version ) (Open Access) BACKGROUND: Both vedolizumab and ustekinumab can be considered for the treatment of Crohn's disease (CD) when anti-TNF treatment fails. However, head-to-head trials are currently not available or planned. AIM: To compare vedolizumab and ustekinumab in Crohn´s disease patients in a prospective registry specifically developed for comparative studies with correction for confounders. METHODS: Crohn´s disease patients, who failed anti-TNF treatment and started vedolizumab or ustekinumab in standard care as second-line biological, were identified in the observational prospective Dutch Initiative on Crohn and Colitis Registry. Corticosteroid-free clinical remission (Harvey Bradshaw Index ≤4), biochemical remission (C-reactive protein ≤5 mg/L and fecal calprotectin ≤250 µg/g), combined corticosteroid-free clinical and biochemical remission, and safety outcomes were compared after 52 weeks of treatment. To adjust for confounding and selection bias, we used multiple logistic regression and propensity score matching. RESULTS: In total, 128 vedolizumab- and 85 ustekinumab-treated patients fulfilled the inclusion criteria. After adjusting for confounders, ustekinumab-treated patients were more likely to achieve corticosteroid-free clinical remission (odds ratio [OR]: 2.58, 95% CI: 1.36-4.90, P = 0.004), biochemical remission (OR: 2.34, 95% CI: 1.10-4.96, P = 0.027), and combined corticosteroid-free clinical and biochemical remission (OR: 2.74, 95% CI: 1.23-6.09, P = 0.014), while safety outcomes (infections: OR: 1.26, 95% CI: 0.63-2.54, P = 0.517; adverse events: OR: 1.33, 95% CI: 0.62-2.81, P = 0.464; hospitalisations: OR: 0.67, 95% CI: 0.32-1.39, P = 0.282) were comparable between the two groups. The propensity score matched cohort with sensitivity analyses showed comparable results. CONCLUSIONS: Ustekinumab was associated with superior effectiveness outcomes when compared to vedolizumab, while safety outcomes were comparable after 52 weeks of treatment in CD patients who have failed anti-TNF treatment.

Published
2020

32. Ustekinumab is associated with superior effectiveness outcomes compared to vedolizumab in Crohn's disease patients with prior failure to anti-TNF treatment

Author

Biemans, VBC, van der Woude, C.J., Dijkstra, G, de Jong, AEE, Lowenberg, M, de Boer, NK, Oldenburg, B, Srivastava, N, Jansen, J, Bodelier, AG, West, rachel, de Vries, Annemarie, Haans, JJL, Jong, D, Hoentjen, F, Pierik, MJ, Biemans, VBC, van der Woude, C.J., Dijkstra, G, de Jong, AEE, Lowenberg, M, de Boer, NK, Oldenburg, B, Srivastava, N, Jansen, J, Bodelier, AG, West, rachel, de Vries, Annemarie, Haans, JJL, Jong, D, Hoentjen, F, and Pierik, MJ

Published
2020

40. IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes

Author

Momozawa, Y, Dmitrieva, J, Theatre, E, Deffontaine, V, Rahmouni, S, Charloteaux, B, Crins, F, Docampo, E, Elansary, M, Gori, AS, Lecut, C, Mariman, R, Mni, M, Oury, C, Altukhov, I, Alexeev, D, Aulchenko, Y, Amininejad, L, Bouma, G, Hoentjen, F, Lowenberg, M, Oldenburg, B, Pierik, MJ, de Jong, AE, van der Woude, C.J., Visschedijk, MC, Lathrop, M, Hugot, JP, Weersma, RK, Vos, M, Franchimont, D, Vermeire, S, Kubo, M, Louis, E, Georges, M, Abraham, C, Achkar, JP, Ahmad, T, Ananthakrishnan, AN, Andersen, V, Anderson, CA, Andrews, JM, Annese, V, Aumais, G, Baidoo, L, Baldassano, RN, Bampton, PA, Barclay, M, Barrett, JC, Bayless, TM, Bethge, J, Bitton, A, Boucher, G, Brand, S, Brandt, B, Brant, SR, Buning, C, Chew, A, Cho, JH, Cleynen, I, Cohain, A, Croft, A, Daly, MJ, D'Amato, M, Danese, S, Jong, D, Denapiene, G, Denson, LA, Devaney, KL, Dewit, O, D'Inca, R, Dubinsky, M, Duerr, RH, Edwards, C, Ellinghaus, D, Essers, J, Ferguson, LR, Festen, EA, Fleshner, P, Florin, T, Franke, A, Fransen, K, Gearry, R, Gieger, C, Glas, J, Goyette, P, Green, T, Griffiths, AM, Guthery, SL, Hakonarson, H, Halfvarson, J, Hanigan, K, Haritunians, T, de Hart, A, Hawkey, C, Hayward, NK, Hedl, M, Henderson, P, Hu, XH, Huang, HL, Hui, KY, Imielinski, M, Ippoliti, A, Jonaitis, L, Jostins, L, Karlsen, TH, Kennedy, NA, Khan, MA, Kiudelis, G, Krishnaprasad, K, Kugathasan, S, Kupcinskas, L, Latiano, A, Laukens, D, Lawrance, IC, Lee, JC, Lees, CW, Leja, M, van Limbergen, J, Lionetti, P, Liu, JZ, Mahy, G, Mansfield, J, Massey, D, Mathew, CG, McGovern, DPB, Milgrom, R, Mitrovic, M, Montgomery, GW, Mowat, C, Newman, W, Ng, A, Ng, SC, Ng, SME, Nikolaus, S, Ning, K, Nothen, M, Oikonomou, I, Palmieri, O, Parkes, M, Phillips, A, Ponsioen, CY, Potocnik, U, Prescott, NJ, Proctor, DD, Radford-Smith, G, Rahier, JF, Raychaudhuri, S, Regueiro, M, Rieder, F, Rioux, JD, Ripke, S, Roberts, R, Russell, RK, Sanderson, JD, Sans, M, Satsangi, J, Schadt, EE, Schreiber, S, Schulte, D, Schumm, LP, Scott, R, Seielstad, M, Sharma, Y, Silverberg, MS, Simms, LA, Skieceviciene, J, Spain, SL, Steinhart, AH, Stempak, JM, Stronati, L, Sventoraityte, J, Targan, SR, Taylor, KM, Velde, A, Torkvist, L, Tremelling, M, van Sommeren, S, Vasiliauskas, E, Verspaget, HW, Walters, T, Wang, K, Wang, MH, Wei, Z, Whiteman, D, Wijmenga, C, Wilson, DC, Winkelmann, J, Xavier, RJ, Zhang, B, Zhang, CK, Zhang, H, Zhang, W, Zhao, HY, Zhao, ZZ, Momozawa, Y, Dmitrieva, J, Theatre, E, Deffontaine, V, Rahmouni, S, Charloteaux, B, Crins, F, Docampo, E, Elansary, M, Gori, A, Lecut, C, Mariman, R, Mni, M, Oury, C, Altukhov, I, Alexeev, D, Aulchenko, Y, Amininejad, L, Bouma, G, Hoentjen, F, Lowenberg, M, Oldenburg, B, Pierik, Mj, vander Meulen-de Jong, Ae, van der Woude, Cj, Visschedijk, Mc, Lathrop, M, Hugot, Jp, Weersma, Rk, De Vos, M, Franchimont, D, Vermeire, S, Kubo, M, Louis, E, Georges, M, Abraham, C, Achkar, Jp, Ahmad, T, Ananthakrishnan, An, Andersen, V, Anderson, Ca, Andrews, Jm, Annese, V, Aumais, G, Baidoo, L, Baldassano, Rn, Bampton, Pa, Barclay, M, Barrett, Jc, Bayless, Tm, Bethge, J, Bitton, A, Boucher, G, Brand, S, Brandt, B, Brant, Sr, Buning, C, Chew, A, Cho, Jh, Cleynen, I, Cohain, A, Croft, A, Daly, Mj, D'Amato, M, Danese, S, De Jong, D, Denapiene, G, Denson, La, Devaney, Kl, Dewit, O, D'Inca, R, Dubinsky, M, Duerr, Rh, Edwards, C, Ellinghaus, D, Essers, J, Ferguson, Lr, Festen, Ea, Fleshner, P, Florin, T, Franke, A, Fransen, K, Gearry, R, Gieger, C, Glas, J, Goyette, P, Green, T, Griffiths, Am, Guthery, Sl, Hakonarson, H, Halfvarson, J, Hanigan, K, Haritunians, T, Hart, A, Hawkey, C, Hayward, Nk, Hedl, M, Henderson, P, Hu, Xh, Huang, Hl, Hui, Ky, Imielinski, M, Ippoliti, A, Jonaitis, L, Jostins, L, Karlsen, Th, Kennedy, Na, Khan, Ma, Kiudelis, G, Krishnaprasad, K, Kugathasan, S, Kupcinskas, L, Latiano, A, Laukens, D, Lawrance, Ic, Lee, Jc, Lees, Cw, Leja, M, Van Limbergen, J, Lionetti, P, Liu, Jz, Mahy, G, Mansfield, J, Massey, D, Mathew, Cg, Mcgovern, Dpb, Milgrom, R, Mitrovic, M, Montgomery, Gw, Mowat, C, Newman, W, Ng, A, Ng, Sc, Ng, Sme, Nikolaus, S, Ning, K, Nothen, M, Oikonomou, I, Palmieri, O, Parkes, M, Phillips, A, Ponsioen, Cy, Potocnik, U, Prescott, Nj, Proctor, Dd, Radford-Smith, G, Rahier, Jf, Raychaudhuri, S, Regueiro, M, Rieder, F, Rioux, Jd, Ripke, S, Roberts, R, Russell, Rk, Sanderson, Jd, Sans, M, Satsangi, J, Schadt, Ee, Schreiber, S, Schulte, D, Schumm, Lp, Scott, R, Seielstad, M, Sharma, Y, Silverberg, M, Simms, La, Skieceviciene, J, Spain, Sl, Steinhart, Ah, Stempak, Jm, Stronati, L, Sventoraityte, J, Targan, Sr, Taylor, Km, ter Velde, A, Torkvist, L, Tremelling, M, van Sommeren, S, Vasiliauskas, E, Verspaget, Hw, Walters, T, Wang, K, Wang, Mh, Wei, Z, Whiteman, D, Wijmenga, C, Wilson, Dc, Winkelmann, J, Xavier, Rj, Zhang, B, Zhang, Ck, Zhang, H, Zhang, W, Zhao, Hy, Zhao, Zz, Gastroenterology & Hepatology, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, and UCL - (MGD) Service de gastro-entérologie

Subjects
Adult, Male, Multifactorial Inheritance, QUANTITATIVE TRAIT LOCUS, Genotype, SEQUENCING DATA, Quantitative Trait Loci, SUSCEPTIBILITY, Polymorphism, Single Nucleotide, Article, Cohort Studies, CODING VARIANTS, Crohn Disease, 80 and over, Journal Article, Medicine and Health Sciences, LOCUS, Humans, Genetic Predisposition to Disease, Polymorphism, GENOME-WIDE ASSOCIATION, Genetic Association Studies, Aged, Aged, 80 and over, Science & Technology, Female, Gene Expression Profiling, Inflammatory Bowel Diseases, Middle Aged, Sequence Analysis, DNA, COMPLEX TRAITS, Biology and Life Sciences, Single Nucleotide, DNA, CROHNS-DISEASE, Multidisciplinary Sciences, QUANTITATIVE TRAIT, RARE VARIANTS, Science & Technology - Other Topics, LOW-FREQUENCY, Sequence Analysis, INFLAMMATORY-BOWEL-DISEASE
Abstract

GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach., Most of the more than 200 known genetic risk loci for inflammatory bowel disease (IBD) reside in regulatory regions. Here, the authors provide eQTL datasets for six circulating immune cell types and ileal, colonic and rectal biopsies to map regulatory modules and identify potential causative genes for IBD.

Published
2018

41. The Impact of Ethnicity and Country of Birth on Inflammatory Bowel Disease Phenotype: a Prospective Cohort Study

Author

Spekhorst, L.M., Severs, M., Boer, N.K.H. de, Festen, E.A.M., Fidder, H.H., Hoentjen, F., Imhann, F., Jong, D.J. de, Meulen-de Jong, A.E. van der, Pierik, M.J., Woude, C.J. van der, Dijkstra, G., Ponsioen, C.Y., Lowenberg, M., Oldenburg, B., Weersma, R.K., Parelsnoer Inst, Dutch Initiative Crohn Colitis, Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Cardio Thoracale Chirurgie, Interne Geneeskunde, MUMC+: MA Maag Darm Lever (9), RS: NUTRIM - R2 - Liver and digestive health, RS: NUTRIM - R2 - Gut-liver homeostasis, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), Groningen Institute for Organ Transplantation (GIOT), AII - Inflammatory diseases, AGEM - Digestive immunity, Gastroenterology and hepatology, and Gastroenterology & Hepatology

Subjects
Male, 0301 basic medicine, Pediatrics, ENVIRONMENTAL RISK-FACTORS, Anal Canal, Constriction, Pathologic, Disease, Inflammatory bowel disease, 0302 clinical medicine, Crohn Disease, Residence Characteristics, Epidemiology, EPIDEMIOLOGY, Prospective Studies, Age of Onset, Prospective cohort study, NON-HISPANIC WHITES, Digestive System Surgical Procedures, POPULATION, Netherlands, education.field_of_study, Crohn's disease, Gastroenterology, General Medicine, Middle Aged, Ulcerative colitis, CROHNS-DISEASE, Europe, ULCERATIVE-COLITIS, ethnicity, Female, 030211 gastroenterology & hepatology, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], Adult, medicine.medical_specialty, PACIFIC, MIGRATION, phenotype, Population, UNITED-STATES, Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], White People, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Intestinal Fistula, medicine, Humans, education, Aged, ulcerative colitis, business.industry, medicine.disease, Non-Hispanic whites, digestive system diseases, 030104 developmental biology, Colitis, Ulcerative, SOUTH ASIANS, business
Abstract

Background and Aims: The number of patients with inflammatory bowel disease [IBD], of non-Caucasian descent in Western Europe, is increasing. We aimed to explore the impact of ethnicity and country of birth on IBD phenotype.Methods: IBD patients treated in the eight University Medical Centers in The Netherlands [Dutch IBD Biobank] were divided into two groups according to their ethnicity: 1] Caucasian patients of Western and Central European descent [CEU]; and 2] patients of non-Caucasian descent [non-CEU]. The non-CEU group was subdivided according to country of birth, into: born in The Netherlands or Western Europe [non-CEU European born]; or born outside Western-Europe who migrated to The Netherlands [non-CEU non-European born]. Both comparisons were analysed for phenotype differences [by chi-square test].Results: The Dutch IBD Biobank included 2921 CEU patients and 233 non-CEU patients. Non-CEU Crohn's disease [CD] patients more often had upper gastro-intestinal disease [16% vs 8%, p = 0.001] and anal stenosis [10% vs 4%, p = 0.002] than CEU CD patients. The use of anti-tumour necrosis factor [TNF] agents and immunomodulators was higher in non-CEU IBD patients than in CEU IBD patients [45% vs 38%, p = 0.042] and [77% vs 66%, p = 0.001], respectively. Non-CEU IBD patients born in Europe [n = 116] were diagnosed at a lower age than non-CEU IBD patients born outside Europe [n = 115] [at 22.7 vs 28.9 years old, p < 0.001].Conclusion: Non-Caucasians had more severe disease behaviour than Caucasians. Non-CEU patients born in Europe were diagnosed at a lower age with IBD than those born outside Europe who migrated to The Netherlands.

Published
2017

42. Experimental investigation of aerodynamic hysteresis using a 5-DoF wind tunnel manoeuvre rig

Author

Gong, Z., Araujo-Estrada, Sergio A., Lowenberg, M. H., Neild, Simon, and Goman, M. (Mikhail G.)

Subjects
Computer Science::Robotics, a lightweight jet trainer aircraft, a 5-DoF wind tunnel manoeuvre rig, aerodynamic static hysteresis, high incidence aerodynamics, Physics::Atmospheric and Oceanic Physics, an onset of aerodynamic asymmetry
Abstract

The file attached to this record is the author's final peer reviewed version. The high-incidence aerodynamics of a lightweight jet trainer aircraft model has been investigated using a novel five-degree-of-freedom (DOF) dynamic maneuver rig, recently updated with improved actuation and data acquisition systems, in the 7 × 5 ft closed-section low-speed wind tunnel at the University of Bristol. The major focus was to identify the nonlinear and unsteady aerodynamic characteristics specific to the stall region and which affect free-to-move aircraft-model behavior. First, the unstable equilibrium states in the limit-cycle regions were stabilized, and so observed, over a wide range of angles of attack using a simple elevator feedback control lawbased on pitch angle and pitch-rate sensor measurements. Tests with two DOF, namely, the aircraft model and rig-arm pitch angles, revealed the existence of static hysteresis in the normal force acting on the aircraft model in the stall region. Unlocking the aircraft model in roll and yaw accompanied by feedback stabilization of the lateral–directional modes of motion demonstrated the onset of asymmetric aerodynamic rolling and yawing moments in this four-DOF configuration. This observation implicitly indicates a link between the static hystereses in the normal aerodynamic force with an onset of aerodynamic asymmetry. The experimental results show the efficiency of the updated multi-DOF actively controlled maneuver rig in providing insight into complicated aerodynamic effects within the stall region.

Published
2018

43. IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes

Author

Momozawa, Y., Dmitrieva, J., Theatre, E., Deffontaine, V., Rahmouni, S., Charloteaux, B., Crins, F., Docampo, E., Elansary, M., Gori, A.S., Lecut, C., Mariman, R., Mni, M., Oury, C., Altukhov, I., Alexeev, D., Aulchenko, Y., Amininejad, L., Bouma, G., Hoentjen, F., Lowenberg, M., Oldenburg, B., Pierik, M.J., vander Meulen-de Jong, A.E., Woude, C.J. van der, Visschedijk, M.C., Lathrop, M., Hugot, J.P., Weersma, R.K., Vos, M. de, Franchimont, D., Vermeire, S., Kubo, M., Louis, E., Georges, M., Abraham, C., Achkar, J.P., Ahmad, T., Ananthakrishnan, A.N., Andersen, V., Anderson, C.A., Andrews, J.M., Annese, V., Aumais, G., Baidoo, L., Baldassano, R.N., Bampton, P.A., Barclay, M., Barrett, J.C., Bayless, T.M., Bethge, J., Bitton, A., Boucher, G., Brand, S., Brandt, B., Brant, S.R., Buning, C., Chew, A., Cho, J.H., Cleynen, I., Cohain, A., Croft, A., Daly, M.J., D'Amato, M., Danese, S., Jong, D. de, Denapiene, G., Denson, L.A., Devaney, K.L., Dewit, O., D'Inca, R., Dubinsky, M., Duerr, R.H., Edwards, C., Ellinghaus, D., Essers, J., Ferguson, L.R., Festen, E.A., Fleshner, P., Florin, T., Franke, A., Fransen, K., Gearry, R., Gieger, C., Glas, J., Goyette, P., Green, T., Griffiths, A.M., Guthery, S.L., Hakonarson, H., Halfvarson, J., Hanigan, K., Haritunians, T., Hart, A., Hawkey, C., Hayward, N.K., Hedl, M., Henderson, P., Hu, X.H., Huang, H.L., Hui, K.Y., Imielinski, M., Ippoliti, A., Jonaitis, L., Jostins, L., Karlsen, T.H., Kennedy, N.A., Khan, M.A., Kiudelis, G., Krishnaprasad, K., Kugathasan, S., Kupcinskas, L., Latiano, A., Laukens, D., Lawrance, I.C., Lee, J.C., Lees, C.W., Leja, M., Limbergen, J. van, Lionetti, P., Liu, J.Z., Mahy, G., Mansfield, J., Massey, D., Mathew, C.G., McGovern, D.P.B., Milgrom, R., Mitrovic, M., Montgomery, G.W., Mowat, C., Newman, W., Ng, A., Ng, S.C., Ng, S.M.E., Nikolaus, S., Ning, K., Nothen, M., Oikonomou, I., Palmieri, O., Parkes, M., Phillips, A., Ponsioen, C.Y., Potocnik, U., Prescott, N.J., Proctor, D.D., Radford-Smith, G., Rahier, J.F., Raychaudhuri, S., Regueiro, M., Rieder, F., Rioux, J.D., Ripke, S., Roberts, R., Russell, R.K., Sanderson, J.D., Sans, M., Satsangi, J., Schadt, E.E., Schreiber, S., Schulte, D., Schumm, L.P., Scott, R., Seielstad, M., Sharma, Y., Silverberg, M.S., Simms, L.A., Skieceviciene, J., Spain, S.L., Steinhart, A.H., Stempak, J.M., Stronati, L., Sventoraityte, J., Targan, S.R., Taylor, K.M., Velde, A. ter, Torkvist, L., Tremelling, M., Sommeren, S. van, Vasiliauskas, E., Verspaget, H.W., Walters, T., Wang, K., Wang, M.H., Wei, Z., Whiteman, D., Wijmenga, C., Wilson, D.C., Winkelmann, J., Xavier, R.J., Zhang, B., Zhang, C.K., Zhang, H., Zhang, W., Zhao, H.Y., Zhao, Z.Z., and Int IBD Genetics Consortium

Published
2018

44. Genomic and Expression Analyses Identify a Disease-Modifying Variant for Fibrostenotic Crohn's Disease

Author

Visschedijk, M.C., Spekhorst, L.M., Cheng, S.C., Loo, E.S. van, Jansen, B.H.D., Blokzijl, T., Kil, H., Jong, D.J. de, Pierik, M., Maljaars, J.P.W.J., Woude, C.J. van der, Bodegraven, A.A. van, Oldenburg, B., Lowenberg, M., Nieuwenhuijs, V.B., Imhann, F., Sommeren, S. van, Alberts, R., Xavier, R.J., Dijkstra, G., Faber, K.N., Aldaz, C.M., Weersma, R.K., Festen, E.A.M., Dutch Initiative Crohn Colitis ICC, Parelsnoer Inst, Gastroenterology and hepatology, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), Center for Liver, Digestive and Metabolic Diseases (CLDM), Groningen Institute for Organ Transplantation (GIOT), Interne Geneeskunde, MUMC+: MA Maag Darm Lever (9), RS: NUTRIM - R2 - Liver and digestive health, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, and Gastroenterology & Hepatology

Subjects
0301 basic medicine, Male, LOCI, Genome-wide association study, Constriction, Pathologic, SUSCEPTIBILITY, Inflammatory bowel disease, 0302 clinical medicine, Crohn Disease, Transforming Growth Factor beta, WIDE ASSOCIATION, genetics, RISK, Gastroenterology, Endoscopic dilatation, General Medicine, Genomics, Crohn's disease, Phenotype, WW Domain-Containing Oxidoreductase, 030211 gastroenterology & hepatology, Female, RNA, Long Noncoding, WWOX, Adult, Adolescent, Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], Single-nucleotide polymorphism, PHENOTYPES, Polymorphism, Single Nucleotide, 03 medical and health sciences, Young Adult, Chromosome 16, Genetics, medicine, Humans, RNA, Messenger, Allele, Alleles, IDENTIFICATION, business.industry, Tumor Suppressor Proteins, fibrosis, Case-control study, medicine.disease, Fibrosis, 030104 developmental biology, Case-Control Studies, Cancer research, VISUALIZATION, INTESTINAL FIBROSIS, business, Genome-Wide Association Study, INFLAMMATORY-BOWEL-DISEASE
Abstract

Item does not contain fulltext Background and Aims: Crohn's disease [CD] is a chronic inflammatory disease with unpredictable behaviour. More than half of CD patients eventually develop complications such as stenosis, for which they then require endoscopic dilatation or surgery, as no anti-fibrotic drugs are currently available. We aim to identify disease-modifying genes associated with fibrostenotic CD. Methods: We performed a within-case analysis comparing 'extreme phenotypes' using the Immunochip and replication of the top single nucleotide polymorphisms [SNPs] with Agena Bioscience in two independent case-control cohorts totalling 322 cases with fibrostenotis [recurrent after surgery] and 619 cases with purely inflammatory CD. Results: Combined meta-analysis resulted in a genome-wide significant signal for SNP rs11861007 [p = 6.0910-11], located on chromosome 16, in lncRNA RP11-679B19.1, an lncRNA of unknown function, and close to exon 9 of the WWOX gene, which codes for WW domain-containing oxidoreductase. We analysed mRNA expression of TGF-beta and downstream genes in ileocecal resection material from ten patients with and without the WWOX risk allele. Patients carrying the risk allele [A] showed enhanced colonic expression of TGF-beta compared to patients homozygous for the wild-type [G] allele [p = 0.0079]. Conclusion: We have identified a variant in WWOX and in lncRNA RP11-679B19.1 as a disease-modifying genetic variant associated with recurrent fibrostenotic CD and replicated this association in an independent cohort. WWOX can potentially play a crucial role in fibrostenosis in CD, being positioned at the crossroads of inflammation and fibrosis.

Published
2018

50. Cohort profile: design and first results of the Dutch IBD Biobank: a prospective, nationwide biobank of patients with inflammatory bowel disease

Author

Spekhorst, L.M., Imhann, F., Festen, E.A.M., Bodegraven, A.A. van, Boer, N.K.H. de, Bouma, G., Fidder, H.H., D'Haens, G., Hoentjen, F., Hommes, D.W., Jong, D.J. de, Lowenberg, M., Maljaars, P.W.J., Meulen-de Jong, A.E. van der, Oldenburg, B., Pierik, M.J., Ponsioen, C.Y., Stokkers, P.C., Verspaget, H.W., Visschedijk, M.C., Woude, C.J. van der, Dijkstra, G., Weersma, R.K., Parelsnoer Institute PSI, Dutch Initiative Crohn Colitis ICC, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), Groningen Institute for Organ Transplantation (GIOT), Immunology, Gastroenterology & Hepatology, Gastroenterology and hepatology, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, Surgery, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, Other departments, Interne Geneeskunde, MUMC+: MA Maag Darm Lever (9), RS: NUTRIM - R2 - Liver and digestive health, and RS: NUTRIM - R2 - Gut-liver homeostasis

Subjects
Male, Crohn’s disease, 0301 basic medicine, Pathology, Genotyping Techniques, INCREASES, EXTRAINTESTINAL MANIFESTATIONS, gastroenterology, Disease, Inflammatory bowel disease, 0302 clinical medicine, Prospective Studies, POPULATION, Biological Specimen Banks, Netherlands, education.field_of_study, Crohn's disease, ASSOCIATION, General Medicine, Biobank, Ulcerative colitis, CROHNS-DISEASE, biobank, ULCERATIVE-COLITIS, Cohort, Disease Progression, Female, 030211 gastroenterology & hepatology, SMOKING, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], Adult, medicine.medical_specialty, SUSCEPTIBILITY LOCI, Population, Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], Gastroenterology and Hepatology, digestive system, CLASSIFICATION, Young Adult, 03 medical and health sciences, inflammatory bowel disease, Internal medicine, Journal Article, medicine, Humans, education, Genotyping, ulcerative colitis, Cohort Profile, business.industry, Inflammatory Bowel Diseases, medicine.disease, digestive system diseases, 030104 developmental biology, RISK-FACTORS, business
Abstract

PurposeThe Dutch IBD Biobank aims to facilitate the discovery of predictors for individual disease course and treatment response in patients with inflammatory bowel disease (IBD). In this paper, we aim to describe the establishment of the Dutch IBD Biobank, including the facilitators and barriers to establishment. Moreover, we aim to provide a complete overview of the content of the Dutch IBD Biobank.ParticipantsSince 2007, every patient with IBD treated in one of the eight Dutch university medical centres is asked to participate in the Dutch IBD Biobank in which 225 standardised IBD-related data items and biomaterials, such as serum, DNA, biopsies and a stool sample, are collected.Findings to dateAs of June 2014, the Dutch IBD Biobank had enrolled 3388 patients with IBD: 2118 Crohn’s disease (62.5%), 1190 ulcerative colitis (35.1%), 74 IBD-unclassified (2.2%) and 6 IBD-indeterminate (0.2%). The inclusion of patients with IBD is ongoing. The quality of the biomaterials is good and serum, DNA and biopsies have been used in newly published studies.Future plansThe genotyping (750 000 genetic variants) of all participants of the Dutch IBD Biobank is currently ongoing, enabling more genetic research. In addition, all participants will start reporting disease activity and outcome measures using an online platform and mobileapp.

Published
2017

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