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127 results on '"Kammermeier, Jochen"'

1. Precision medicine in monogenic inflammatory bowel disease: proposed mIBD REPORT standards

Author

Uhlig, Holm H., Booth, Claire, Cho, Judy, Dubinsky, Marla, Griffiths, Anne M., Grimbacher, Bodo, Hambleton, Sophie, Huang, Ying, Jones, Kelsey, Kammermeier, Jochen, Kanegane, Hirokazu, Koletzko, Sibylle, Kotlarz, Daniel, Klein, Christoph, Lenardo, Michael J., Lo, Bernice, McGovern, Dermot P. B., Özen, Ahmet, de Ridder, Lissy, Ruemmele, Frank, Shouval, Dror S., Snapper, Scott B., Travis, Simon P., Turner, Dan, Wilson, David C., and Muise, Aleixo M.

Published
2023
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3. Phenotypic stratification and molecular characterisation of inflammatory bowel disease presenting in early childhood

Author

Kammermeier, Jochen

Abstract

Genome wide association studies in inflammatory bowel disease (IBD) highlighted the contribution of common genetic variants to the disease pathogenicity of IBD. Overall combined genetic variation in IBD across the age spectrum however still fails to explain the majority of IBD heritability. First publications of young children with IBD-like phenotype due to underlying monogenic diseases affecting the immune system raised the awareness of Mendelian disorder associated IBD (MDIBD). Although overall rare, the clinical impact of a timely molecular diagnosis was evident for individual patients with immune deficiencies amenable to curative haematopoietic stem cell transplantation. In my research, I investigated the phenotype of IBD presenting in early childhood and evaluated novel next generation sequencing (NGS) platforms to screen for MDIBD. My research led to the first publication of targeted gene panel sequencing (TGPS) for children with suspected MDIBD. The North-East Thames Regional Genetic Laboratory has since integrated TGPS into the routine clinical work up for young children with IBD. I have subsequently analysed transcriptomic data from peripheral blood mononuclear cells and gut biopsies. My results suggest that transcriptomics can highlight the biological compartment affected by a pathogenic variant in patients with MDIBD. Being part of an international working group, we were able to curate and publish the first comprehensive list of MDIBD genes and to establish phenotypic features suggestive of underlying monogenic disease. The main emphasis for the future is to ensure genomic screening is made available for all patients with suspected MDIBD. This will require optimised work flows and the development of national expert hubs to interpret genetic results and feedback clinically relevant information to enable best possible clinical outcome for our patients. Furthermore, we need to strengthen international MDIBD initiatives, to develop a unified nomenclature and facilitate multicentre research into rare monogenic conditions with IBD-like phenotype.

Published
2021

4. Genomic diagnosis and care co-ordination for monogenic inflammatory bowel disease in children and adults: consensus guideline on behalf of the British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition

Author

Kammermeier, Jochen, Lamb, Christopher A, Jones, Kelsey D J, Anderson, Carl A, Baple, Emma L, Bolton, Chrissy, Braggins, Helen, Coulter, Tanya I, Gilmour, Kimberly C, Gregory, Vicki, Hambleton, Sophie, Hartley, David, Hawthorne, A Barney, Hearn, Sarah, Laurence, Arian, Parkes, Miles, Russell, Richard K, Speight, R Alexander, Travis, Simon, Wilson, David C, and Uhlig, Holm H

Published
2023
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5. Author Correction: Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Author

Serra, Eva Gonçalves, Schwerd, Tobias, Moutsianas, Loukas, Cavounidis, Athena, Fachal, Laura, Pandey, Sumeet, Kammermeier, Jochen, Croft, Nicholas M., Posovszky, Carsten, Rodrigues, Astor, Russell, Richard K., Barakat, Farah, Auth, Marcus K. H., Heuschkel, Robert, Zilbauer, Matthias, Fyderek, Krzysztof, Braegger, Christian, Travis, Simon P., Satsangi, Jack, Parkes, Miles, Thapar, Nikhil, Ferry, Helen, Matte, Julie C., Gilmour, Kimberly C., Wedrychowicz, Andrzej, Sullivan, Peter, Moore, Carmel, Sambrook, Jennifer, Ouwehand, Willem, Roberts, David, Danesh, John, Baeumler, Toni A., Fulga, Tudor A., Carrami, Eli M, Ahmed, Ahmed, Wilson, Rachel, Barrett, Jeffrey C., Elkadri, Abdul, Griffiths, Anne M., Snapper, Scott B., Shah, Neil, Muise, Aleixo M., Wilson, David C., Uhlig, Holm H., and Anderson, Carl A.

Published
2022
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6. An Integrated Taxonomy for Monogenic Inflammatory Bowel Disease

Author

Bolton, Chrissy, Smillie, Christopher S., Pandey, Sumeet, Elmentaite, Rasa, Wei, Gabrielle, Argmann, Carmen, Aschenbrenner, Dominik, James, Kylie R., McGovern, Dermot P.B., Macchi, Marina, Cho, Judy, Shouval, Dror S., Kammermeier, Jochen, Koletzko, Sibylle, Bagalopal, Krithika, Capitani, Melania, Cavounidis, Athena, Pires, Elisabete, Weidinger, Carl, McCullagh, James, Arkwright, Peter D., Haller, Wolfram, Siegmund, Britta, Peters, Lauren, Jostins, Luke, Travis, Simon P.L., Anderson, Carl A., Snapper, Scott, Klein, Christoph, Schadt, Eric, Zilbauer, Matthias, Xavier, Ramnik, Teichmann, Sarah, Muise, Aleixo M., Regev, Aviv, and Uhlig, Holm H.

Published
2022
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7. SARS-CoV-2 vaccination for patients with inflammatory bowel disease: a British Society of Gastroenterology Inflammatory Bowel Disease section and IBD Clinical Research Group position statement

Author

Norton, Christine, Din, Shahida, Glatter, Jackie, Kammermeier, Jochen, Ramdeen, Madhoor, Quraishi, Nabil, Sagar, Peter, Radford, Shellie, Speight, R. Alexander, Steed, Helen, Mcfarlane, Michael, Hawthorne, A. Barney, Alexander, James L, Moran, Gordon W, Gaya, Daniel R, Raine, Tim, Hart, Ailsa, Kennedy, Nicholas A, Lindsay, James O, MacDonald, Jonathan, Segal, Jonathan P, Sebastian, Shaji, Selinger, Christian P, Parkes, Miles, Smith, Philip J, Dhar, Anjan, Subramanian, Sreedhar, Arasaradnam, Ramesh, Lamb, Christopher A, Ahmad, Tariq, Lees, Charlie W, Dobson, Liz, Wakeman, Ruth, Iqbal, Tariq H, Arnott, Ian, and Powell, Nick

Published
2021
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9. Top 10 research priorities for digital technology for adolescents and young persons with inflammatory bowel disease: Results of a James Lind Alliance Priority Setting Partnership.

Author

Narula, Priya, Gasparetto, Marco, Wong, Charlotte, Branchflower, Jacob, Sebastian, Shaji, McLaughlin, John, Rao, Arati, Wakeman, Ruth, Ainley, Rachel, Smith, Philip J., Kammermeier, Jochen, Younge, Lisa, Randall, Sophie, Bukhari, Seema, Manson, Jess, Ellis, Patricia, and Arebi, Naila

Published
2024
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10. Variation in access and prescription of vedolizumab and ustekinumab in paediatric patients with inflammatory bowel disease: a UK-wide study

Author

Auth, Marcus Karl-Heinz, primary, Ashton, James John, additional, Jones, Kelsey D J, additional, Rodrigues, Astor, additional, Thangarajah, Dhamyanthi, additional, Devadason, David, additional, Lee, Gemma, additional, Ayaz, Mashhood, additional, Lee, Huey Miin, additional, and Kammermeier, Jochen, additional

Published
2023
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11. Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Author

Serra, Eva Gonçalves, Schwerd, Tobias, Moutsianas, Loukas, Cavounidis, Athena, Fachal, Laura, Pandey, Sumeet, Kammermeier, Jochen, Croft, Nicholas M., Posovszky, Carsten, Rodrigues, Astor, Russell, Richard K., Barakat, Farah, Auth, Marcus K. H., Heuschkel, Robert, Zilbauer, Matthias, Fyderek, Krzysztof, Braegger, Christian, Travis, Simon P., Satsangi, Jack, Parkes, Miles, Thapar, Nikhil, Ferry, Helen, Matte, Julie C., Gilmour, Kimberly C., Wedrychowicz, Andrzej, Sullivan, Peter, Moore, Carmel, Sambrook, Jennifer, Ouwehand, Willem, Roberts, David, Danesh, John, Baeumler, Toni A., Fulga, Tudor A., Carrami, Eli M., Ahmed, Ahmed, Wilson, Rachel, Barrett, Jeffrey C., Elkadri, Abdul, Griffiths, Anne M., Snapper, Scott B., Shah, Neil, Muise, Aleixo M., Wilson, David C., Uhlig, Holm H., and Anderson, Carl A.

Published
2020
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12. Enhanced TH17 Responses in Patients with IL10 Receptor Deficiency and Infantile-onset IBD

Author

Shouval, Dror S., Konnikova, Liza, Griffith, Alexandra E., Wall, Sarah M., Biswas, Amlan, Werner, Lael, Nunberg, Moran, Kammermeier, Jochen, Goettel, Jeremy A., Anand, Rajsavi, Chen, Hannah, Weiss, Batia, Li, Jian, Loizides, Anthony, Yerushalmi, Baruch, Yanagi, Tadahiro, Beier, Rita, Conklin, Laurie S., Ebens, Christen L., Santos, Fernanda G. M. S., Sherlock, Mary, Goldsmith, Jeffery D., Kotlarz, Daniel, Glover, Sarah C., Shah, Neil, Bousvaros, Athos, Uhlig, Holm H., Muise, Aleixo M., Klein, Christoph, and Snapper, Scott B.

Published
2017
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15. Thromboprophylaxis Use in Paediatric Inflammatory Bowel Disease: An International RAND Appropriateness Panel

Author

Torrente, Franco, primary, Meade, Susanna, additional, Benchimol, Eric I, additional, de Ridder, Lissy, additional, Croft, Nicholas M, additional, Kammermeier, Jochen, additional, Mack, David R, additional, Klomberg, Renz C W, additional, Turner, Dan, additional, Wilson, David C, additional, Martín-de-Carpi, Javier, additional, Bronsky, Jiri, additional, Amil Dias, Jorge, additional, Walker, Gregor, additional, van Ommen, C Heleen, additional, Powar, Michael P, additional, Burgess, Natasha, additional, Irving, Peter M, additional, Samaan, Mark A, additional, and Hansen, Richard, additional

Published
2022
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16. Author Correction: Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease.

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Serra, Eva Gonçalves, Schwerd, Tobias, Moutsianas, Loukas, Cavounidis, Athena, Fachal, Laura, Pandey, Sumeet, Kammermeier, Jochen, Croft, Nicholas M, Posovszky, Carsten, Rodrigues, Astor, Russell, Richard K, Barakat, Farah, Auth, Marcus K H, Heuschkel, Robert, Zilbauer, Matthias, Fyderek, Krzysztof, Braegger, Christian, Travis, Simon P, Satsangi, Jack, Parkes, Miles, Thapar, Nikhil, Ferry, Helen, Matte, Julie C, Gilmour, Kimberly C, Wedrychowicz, Andrzej, Sullivan, Peter, Moore, Carmel, Sambrook, Jennifer, Ouwehand, Willem, Roberts, David, Danesh, John, Baeumler, Toni A, Fulga, Tudor A, Carrami, Eli M, Ahmed, Ahmed, Wilson, Rachel, Barrett, Jeffrey C, Elkadri, Abdul, Griffiths, Anne M, COLORS in IBD group investigators, Oxford IBD cohort study investigators, INTERVAL Study, Swiss IBD cohort investigators, UK IBD Genetics Consortium, NIDDK IBD Genetics Consortium, Snapper, Scott B, Shah, Neil, Muise, Aleixo M, Wilson, David C, Uhlig, Holm H, Anderson, Carl A, Marot, Astrid, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Serra, Eva Gonçalves, Schwerd, Tobias, Moutsianas, Loukas, Cavounidis, Athena, Fachal, Laura, Pandey, Sumeet, Kammermeier, Jochen, Croft, Nicholas M, Posovszky, Carsten, Rodrigues, Astor, Russell, Richard K, Barakat, Farah, Auth, Marcus K H, Heuschkel, Robert, Zilbauer, Matthias, Fyderek, Krzysztof, Braegger, Christian, Travis, Simon P, Satsangi, Jack, Parkes, Miles, Thapar, Nikhil, Ferry, Helen, Matte, Julie C, Gilmour, Kimberly C, Wedrychowicz, Andrzej, Sullivan, Peter, Moore, Carmel, Sambrook, Jennifer, Ouwehand, Willem, Roberts, David, Danesh, John, Baeumler, Toni A, Fulga, Tudor A, Carrami, Eli M, Ahmed, Ahmed, Wilson, Rachel, Barrett, Jeffrey C, Elkadri, Abdul, Griffiths, Anne M, COLORS in IBD group investigators, Oxford IBD cohort study investigators, INTERVAL Study, Swiss IBD cohort investigators, UK IBD Genetics Consortium, NIDDK IBD Genetics Consortium, Snapper, Scott B, Shah, Neil, Muise, Aleixo M, Wilson, David C, Uhlig, Holm H, Anderson, Carl A, and Marot, Astrid

Published
2022

17. Thromboprophylaxis Use in Paediatric Inflammatory Bowel Disease:An International RAND Appropriateness Panel

Author

Torrente, Franco, Meade, Susanna, Benchimol, Eric I., de Ridder, Lissy, Croft, Nicholas M., Kammermeier, Jochen, Mack, David R., Klomberg, Renz C.W., Turner, Dan, Wilson, David C., Martín-de-Carpi, Javier, Bronsky, Jiri, Amil Dias, Jorge, Walker, Gregor, van Ommen, C. Heleen, Powar, Michael P., Burgess, Natasha, Irving, Peter M., Samaan, Mark A., Hansen, Richard, Torrente, Franco, Meade, Susanna, Benchimol, Eric I., de Ridder, Lissy, Croft, Nicholas M., Kammermeier, Jochen, Mack, David R., Klomberg, Renz C.W., Turner, Dan, Wilson, David C., Martín-de-Carpi, Javier, Bronsky, Jiri, Amil Dias, Jorge, Walker, Gregor, van Ommen, C. Heleen, Powar, Michael P., Burgess, Natasha, Irving, Peter M., Samaan, Mark A., and Hansen, Richard

Abstract

BACKGROUND AND AIMS: Thromboprophylaxis use in paediatric inflammatory bowel disease [IBD] is inconsistent. Current guidelines only support treating children with acute severe colitis with risk factors. We convened an international RAND panel to explore thromboprophylaxis in paediatric IBD inpatients in the context of new evidence. METHODS: We convened a geographically diverse 14-person panel of paediatric gastroenterologists alongside supporting experts. An online survey was sent before an online meeting. Panellists were asked to rate the appropriateness of thromboprophylaxis in hospitalised paediatric IBD patients via 27 scenarios of varying ages, gender, and phenotype, with and without thrombotic risk factors. Anonymised results were presented at the meeting. A second modified survey was distributed to all panellists present at the meeting. Results from the second survey constitute the RAND panel results. The validated RAND disagreement index defined disagreement when ≥ 1. RESULTS: The combined outcome of thromboprophylaxis being considered appropriate until discharge and inappropriate to withhold was seen in 20 of 27 scenarios, including: all patients with new-onset acute severe colitis; all flares of known ulcerative colitis, irrespective of risk factors except in pre-pubescent patients with limited disease and no risk factors; and all Crohn's patients with risk factors. Disagreement was seen in five scenarios regarding Crohn's without risk factors, where outcomes were already uncertain. CONCLUSIONS: RAND panels are an established method to assess expert opinion in areas of limited evidence. This work therefore constitutes neither a guideline nor a consensus; however, the findings suggest a need to re-evaluate the role of thromboprophylaxis in future guidelines.

Published
2022

18. Phenotypic and Genotypic Characterisation of Inflammatory Bowel Disease Presenting Before the Age of 2 years

Author

Kammermeier, Jochen, Dziubak, Robert, Pescarin, Matilde, Drury, Suzanne, Godwin, Heather, Reeve, Kate, Chadokufa, Sibongile, Huggett, Bonita, Sider, Sara, James, Chela, Acton, Nikki, Cernat, Elena, Gasparetto, Marco, Noble-Jamieson, Gabi, Kiparissi, Fevronia, Elawad, Mamoun, Beales, Phil L., Sebire, Neil J., Gilmour, Kimberly, Uhlig, Holm H., Bacchelli, Chiara, and Shah, Neil

Published
2017
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20. IBD 9 Research priorities in digital technology for adolescents and young persons with Inflammatory Bowel Disease: a James Lind Alliance Priority Setting Partnership

Author

Rao, Arati, primary, Wong, Charlotte, additional, Kalli, Antony, additional, Manson, Jess, additional, McLaughlin, John, additional, Younge, Lisa, additional, Kammermeier, Jochen, additional, Lee, Gemma, additional, Gasparetto, Marco, additional, Shaji, Seb, additional, Wakeman, Ruth, additional, Ainley, Rachel, additional, Smith, Philip, additional, Randall, Sophie, additional, Arebi, Naila, additional, Howsley, Philippa, additional, and Narula, Priya, additional

Published
2022
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22. Management of ulcerative colitis

Author

Fell, John M, Muhammed, Rafeeq, Spray, Chris, Crook, Kay, Russell, Richard K, Kammermeier, Jochen, Garrick, Vikki, Auth, Marcus, Morris, Mary-Anne, Bunn, Su, Furman, Mark, and Rodrigues, Astor

Published
2016
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23. Management of Crohnʼs disease

Author

Kammermeier, Jochen, Morris, Mary-Anne, Garrick, Vikki, Furman, Mark, Rodrigues, Astor, Russell, Richard K, Fell, John M, Muhammed, Rafeeq, Spray, Christine, Crooke, Kay, Bunn, Su, and Auth, Marcus

Published
2016
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27. Inflammatory bowel disease clinical service recovery during the COVID-19 pandemic

Author

Din, Shahida, primary, Gaya, Daniel, additional, Kammermeier, Jochen, additional, Lamb, Christopher A, additional, Macdonald, Jonathan, additional, Moran, Gordon, additional, Parkes, Gareth, additional, Pollok, Richard, additional, Sebastian, Shaji, additional, Segal, Jonathan, additional, Selinger, Christian, additional, Smith, Philip J, additional, Steed, Helen, additional, and Arnott, Ian D, additional

Published
2021
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28. Transition Services for Paediatric Inflammatory Bowel Disease: A Multicentre Study of Practice in the United Kingdom

Author

Ashton, James J., primary, Narula, Priya, additional, Kiparissi, Fevronia, additional, Spray, Christine, additional, Wilson, David C., additional, Tayler, Rachel, additional, Howarth, Lucy, additional, Torrente, Franco, additional, Deb, Protima, additional, Cameron, Fiona L., additional, Muhammed, Rafeeq, additional, Paul, Thankam, additional, Epstein, Jenny, additional, Lawson, Maureen, additional, Maginnis, Janis, additional, Zamvar, Veena, additional, Fagbemi, Andrew, additional, Devadason, David, additional, Bhavsar, Hemant S., additional, Kammermeier, Jochen, additional, and Beattie, Robert M., additional

Published
2021
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30. SARS-CoV-2 vaccination for patients with inflammatory bowel disease: a British Society of Gastroenterology Inflammatory Bowel Disease section and IBD Clinical Research Group position statement

Author

Alexander, James L, primary, Moran, Gordon W, additional, Gaya, Daniel R, additional, Raine, Tim, additional, Hart, Ailsa, additional, Kennedy, Nicholas A, additional, Lindsay, James O, additional, MacDonald, Jonathan, additional, Segal, Jonathan P, additional, Sebastian, Shaji, additional, Selinger, Christian P, additional, Parkes, Miles, additional, Smith, Philip J, additional, Dhar, Anjan, additional, Subramanian, Sreedhar, additional, Arasaradnam, Ramesh, additional, Lamb, Christopher A, additional, Ahmad, Tariq, additional, Lees, Charlie W, additional, Dobson, Liz, additional, Wakeman, Ruth, additional, Iqbal, Tariq H, additional, Arnott, Ian, additional, Powell, Nick, additional, Norton, Christine, additional, Din, Shahida, additional, Glatter, Jackie, additional, Kammermeier, Jochen, additional, Ramdeen, Madhoor, additional, Quraishi, Nabil, additional, Sagar, Peter, additional, Radford, Shellie, additional, Speight, R. Alexander, additional, Steed, Helen, additional, Mcfarlane, Michael, additional, and Hawthorne, A. Barney, additional

Published
2021
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31. Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease.

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Serra, Eva Gonçalves, Schwerd, Tobias, Moutsianas, Loukas, Cavounidis, Athena, Fachal, Laura, Pandey, Sumeet, Kammermeier, Jochen, Croft, Nicholas M, Posovszky, Carsten, Rodrigues, Astor, Russell, Richard K, Barakat, Farah, Auth, Marcus K H, Heuschkel, Robert, Zilbauer, Matthias, Fyderek, Krzysztof, Braegger, Christian, Travis, Simon P, Satsangi, Jack, Parkes, Miles, Thapar, Nikhil, Ferry, Helen, Matte, Julie C, Gilmour, Kimberly C, Wedrychowicz, Andrzej, Sullivan, Peter, Moore, Carmel, Sambrook, Jennifer, Ouwehand, Willem, Roberts, David, Danesh, John, Baeumler, Toni A, Fulga, Tudor A, Karaminejadranjbar, Mohammad, Ahmed, Ahmed, Wilson, Rachel, Barrett, Jeffrey C, Elkadri, Abdul, Griffiths, Anne M, COLORS in IBD group investigators, Oxford IBD cohort study investigators, INTERVAL Study, Swiss IBD cohort investigators, UK IBD Genetics Consortium, NIDDK IBD Genetics Consortium, Snapper, Scott B, Shah, Neil, Muise, Aleixo M, Wilson, David C, Uhlig, Holm H, Anderson, Carl A, Marot, Astrid, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Serra, Eva Gonçalves, Schwerd, Tobias, Moutsianas, Loukas, Cavounidis, Athena, Fachal, Laura, Pandey, Sumeet, Kammermeier, Jochen, Croft, Nicholas M, Posovszky, Carsten, Rodrigues, Astor, Russell, Richard K, Barakat, Farah, Auth, Marcus K H, Heuschkel, Robert, Zilbauer, Matthias, Fyderek, Krzysztof, Braegger, Christian, Travis, Simon P, Satsangi, Jack, Parkes, Miles, Thapar, Nikhil, Ferry, Helen, Matte, Julie C, Gilmour, Kimberly C, Wedrychowicz, Andrzej, Sullivan, Peter, Moore, Carmel, Sambrook, Jennifer, Ouwehand, Willem, Roberts, David, Danesh, John, Baeumler, Toni A, Fulga, Tudor A, Karaminejadranjbar, Mohammad, Ahmed, Ahmed, Wilson, Rachel, Barrett, Jeffrey C, Elkadri, Abdul, Griffiths, Anne M, COLORS in IBD group investigators, Oxford IBD cohort study investigators, INTERVAL Study, Swiss IBD cohort investigators, UK IBD Genetics Consortium, NIDDK IBD Genetics Consortium, Snapper, Scott B, Shah, Neil, Muise, Aleixo M, Wilson, David C, Uhlig, Holm H, Anderson, Carl A, and Marot, Astrid

Abstract

Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis.

Published
2020

32. Adaptations to the current ECCO/ESPGHAN guidelines on the management of paediatric acute severe colitis in the context of the COVID-19 pandemic: a RAND appropriateness panel

Author

Hansen, Richard, primary, Meade, Susanna, additional, Beattie, R Mark, additional, Auth, Marcus KH, additional, Croft, Nick, additional, Davies, Philip, additional, Devadason, David, additional, Doherty, Conor, additional, Epstein, Jenny, additional, Howarth, Lucy, additional, Kiparissi, Fevronia, additional, Muhammed, Rafeeq, additional, Shivamurthy, Vinay, additional, Spray, Christine, additional, Stanton, Michael P, additional, Torrente, Franco, additional, Urs, Arun, additional, Wilson, David, additional, Irving, Peter M, additional, Samaan, Mark, additional, and Kammermeier, Jochen, additional

Published
2020
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33. Impact of COVID-19 on diagnosis and management of paediatric inflammatory bowel disease during lockdown: a UK nationwide study

Author

Ashton, James John, primary, Kammermeier, Jochen, additional, Spray, Christine, additional, Russell, Richard K, additional, Hansen, Richard, additional, Howarth, Lucy J, additional, Torrente, Franco, additional, Deb, Protima, additional, Renji, Elizabeth, additional, Muhammed, Rafeeq, additional, Paul, Thankam, additional, Kiparissi, Fevronia, additional, Epstein, Jenny, additional, Lawson, Maureen, additional, Hope, Ben, additional, Zamvar, Veena, additional, Narula, Priya, additional, Kadir, Ahmed, additional, Devadason, David, additional, Bhavsar, Hemant, additional, and Beattie, Robert Mark, additional

Published
2020
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34. NOX1 loss-of-function genetic variants in patients with inflammatory bowel disease

Author

Schwerd, T., Bryant, R. V., Pandey, S., Capitani, M., Meran, L., Cazier, J. -B., Jung, J., Mondal, K., Parkes, M., Mathew, C. G., Fiedler, K., McCarthy, D. J., Sullivan, P. B., Rodrigues, A., Travis, S. P. L., Moore, C., Sambrook, J., Ouwehand, W. H., Roberts, D. J., Danesh, J., Russell, R. K., Wilson, D. C., Kelsen, J. R., Cornall, R., Denson, L. A., Kugathasan, S., Knaus, U. G., Serra, E. G., Anderson, C. A., Duerr, R. H., McGovern, D. P. B., Cho, J., Powrie, Fiona, Li, V. S. W., Muise, A. M., Uhlig, H. H., Donnelly, P., Bell, J., Bentley, D., McVean, G., Ratcliffe, P., Taylor, J., Wilkie, A. O. M., Broxholme, J., Buck, D., Gregory, L., Gregory, J., Lunter, G., Tomlinson, I., Allan, C., Attar, M., Green, A., Humphray, S., Kingsbury, Z., Lamble, S., Lonie, L., Pagnamenta, A., Piazza, P., Polanco, G., Trebes, A., Copley, R., Fiddy, S., Grocock, R., Hatton, E., Holmes, C., Hughes, L., Humburg, P., Kanapin, A., Lise, S., Martin, H., Murray, L., McCarthy, D., Rimmer, A., Sahgal, N., Wright, B., Yau, C., Arancibia, Carolina, Bailey, Adam, Barnes, Ellie, Bird-Lieberman, Beth, Brain, Oliver, Braden, Barbara, Collier, Jane, East, James, Geremia, Alessandra, Howarth, Lucy, Keshav, Satish, Klenerman, Paul, Leedham, Simon, Palmer, Rebecca, Rodrigues, Astor, Simmons, Alison, Sullivan, Peter B, Travis, Simon P L, Uhlig, Holm H, Heuschkel, Rob, Zilbauer, Matthias, Auth, Marcus K. H., Shah, Neil, Kammermeier, Jochen, Croft, Nick, Barakat, Farah, Russell, Richard K., Wilson, David C., Henderson, Paul, Braegger, Christian P., Posovszky, Carsten, Fyderek, Krzysztof, Wedrychowicz, Andrzej, Zurek, Marlen, Strisciuglio, Caterina, Elawad, Mamoun, Lo, Bernice, Parkes, Miles, Satsangi, Jack, Anderson, Carl A., Jostins, L., Kennedy, N. A., Lamb, C. A., Ahmad, T., Edwards, C., Hart, A., Hawkey, C., Mansfield, J. C., Mowat, C., Newman, W. G., Satsangi, J., Simmons, A., Tremelling, M., Lee, J. C., Prescott, N. J., Lees, C. W., Barrett, J. C., UK IBD Genetics Consortium, COLORS in IBD, Oxford IBD cohort study investigators, WGS500 Consortium, INTERVAL Study, Schwerd, T., Bryant, R. V., Pandey, S., Capitani, M., Meran, L., Cazier, J. -B., Jung, J., Mondal, K., Parkes, M., Mathew, C. G., Fiedler, K., Mccarthy, D. J., Sullivan, P. B., Rodrigues, A., Travis, S. P. L., Moore, C., Sambrook, J., Ouwehand, W. H., Roberts, D. J., Danesh, J., Russell, R. K., Wilson, D. C., Kelsen, J. R., Cornall, R., Denson, L. A., Kugathasan, S., Knaus, U. G., Serra, E. G., Anderson, C. A., Duerr, R. H., Mcgovern, D. P. B., Cho, J., Powrie, Fiona, Li, V. S. W., Muise, A. M., Uhlig, H. H., Donnelly, P., Bell, J., Bentley, D., Mcvean, G., Ratcliffe, P., Taylor, J., Wilkie, A. O. M., Broxholme, J., Buck, D., Gregory, L., Gregory, J., Lunter, G., Tomlinson, I., Allan, C., Attar, M., Green, A., Humphray, S., Kingsbury, Z., Lamble, S., Lonie, L., Pagnamenta, A., Piazza, P., Polanco, G., Trebes, A., Copley, R., Fiddy, S., Grocock, R., Hatton, E., Holmes, C., Hughes, L., Humburg, P., Kanapin, A., Lise, S., Martin, H., Murray, L., Mccarthy, D., Rimmer, A., Sahgal, N., Wright, B., Yau, C., Arancibia, Carolina, Bailey, Adam, Barnes, Ellie, Bird-Lieberman, Beth, Brain, Oliver, Braden, Barbara, Collier, Jane, East, Jame, Geremia, Alessandra, Howarth, Lucy, Keshav, Satish, Klenerman, Paul, Leedham, Simon, Palmer, Rebecca, Rodrigues, Astor, Simmons, Alison, Sullivan, Peter B, Travis, Simon P L, Uhlig, Holm H, Heuschkel, Rob, Zilbauer, Matthia, Auth, Marcus K. H., Shah, Neil, Kammermeier, Jochen, Croft, Nick, Barakat, Farah, Russell, Richard K., Wilson, David C., Henderson, Paul, Braegger, Christian P., Posovszky, Carsten, Fyderek, Krzysztof, Wedrychowicz, Andrzej, Zurek, Marlen, Strisciuglio, Caterina, Elawad, Mamoun, Lo, Bernice, Parkes, Mile, Satsangi, Jack, Anderson, Carl A., Jostins, L., Kennedy, N. A., Lamb, C. A., Ahmad, T., Edwards, C., Hart, A., Hawkey, C., Mansfield, J. C., Mowat, C., Newman, W. G., Satsangi, J., Simmons, A., Tremelling, M., Lee, J. C., Prescott, N. J., Lees, C. W., Barrett, J. C., UK IBD Genetics, Consortium, COLORS in, Ibd, Oxford IBD cohort study, Investigator, Wgs500, Consortium, and Interval, Study

Subjects
Male, Genotype, Colon, Immunology, Mutation, Missense, Genetic Association Studie, Polymorphism, Single Nucleotide, Article, Mice, Animals, Humans, Immunology and Allergy, Genetic Predisposition to Disease, Child, Genetic Association Studies, Genes, Modifier, Genome, Animal, Inflammatory Bowel Disease, High-Throughput Nucleotide Sequencing, Inflammatory Bowel Diseases, digestive system diseases, Host-Pathogen Interaction, Mice, Inbred C57BL, Child, Preschool, Host-Pathogen Interactions, NADPH Oxidase 1, Reactive Oxygen Species, Reactive Oxygen Specie, Human
Abstract

Genetic defects that affect intestinal epithelial barrier function can present with very early-onset inflammatory bowel disease (VEOIBD). Using whole-genome sequencing, a novel hemizygous defect in NOX1 encoding NAPDH oxidase 1 was identified in a patient with ulcerative colitis-like VEOIBD. Exome screening of 1,878 pediatric patients identified further seven male inflammatory bowel disease (IBD) patients with rare NOX1 mutations. Loss-of-function was validated in p.N122H and p.T497A, and to a lesser degree in p.Y470H, p.R287Q, p.I67M, p.Q293R as well as the previously described p.P330S, and the common NOX1 SNP p.D360N (rs34688635) variant. The missense mutation p.N122H abrogated reactive oxygen species (ROS) production in cell lines, ex vivo colonic explants, and patient-derived colonic organoid cultures. Within colonic crypts, NOX1 constitutively generates a high level of ROS in the crypt lumen. Analysis of 9,513 controls and 11,140 IBD patients of non-Jewish European ancestry did not reveal an association between p.D360N and IBD. Our data suggest that loss-of-function variants in NOX1 do not cause a Mendelian disorder of high penetrance but are a context-specific modifier. Our results implicate that variants in NOX1 change brush border ROS within colonic crypts at the interface between the epithelium and luminal microbes.

Published
2018

37. Management of pneumatosis intestinalis in children over the age of 6 months: a conservative approach

Author

David Thompson, Mohamed Mutalib, Manasvi Upadhyaya, Kammermeier Jochen, and Leel Nellihela

Subjects
Male, Pediatrics, medicine.medical_specialty, Abdominal pain, Adolescent, Conservative Treatment, Asymptomatic, 03 medical and health sciences, 0302 clinical medicine, Pneumoperitoneum, Pneumatosis Cystoides Intestinalis, medicine, Humans, Pneumatosis intestinalis, Child, Retrospective Studies, business.industry, Infant, Retrospective cohort study, Abdominal distension, Short bowel syndrome, medicine.disease, Surgery, Treatment Outcome, 030220 oncology & carcinogenesis, Child, Preschool, Pediatrics, Perinatology and Child Health, 030211 gastroenterology & hepatology, Female, medicine.symptom, business
Abstract

BackgroundPneumatosis intestinalis (PI) is an uncommon and poorly understood condition. Although it can be an incidental finding in asymptomatic individuals, it can also be secondary to life-threatening bowel ischaemia and sepsis. In premature infants, it is a pathognomonic sign of necrotising enterocolitis. There is no consensus regarding management and long-term outcome of children with PI.AimReview of our experience of PI in children beyond the early infantile period.MethodsRetrospective review of patient’s records and radiological images from 2013 to 2015.ResultsEighteen patients (three girls) had radiologically confirmed PI. The median age was 4.5 years (range 8 months–13 years). Background medical conditions (number): short bowel syndrome (one), congenital heart disease (two), sickle cell disease (one), epilepsy (three), cerebral palsy (six), myotonic dystrophy (four) and peroxisomal biogenesis defect (one).Six children (33%) presented with abdominal distension, four (22%) with abdominal pain, three (17%) with bilious vomiting, two (11%) with diarrhoea and one (6%) with rectal bleeding. Two (11%) were asymptomatic. One had air in portal vein and two had pneumoperitoneum.All patients with symptomatic PI were treated conservatively with successful outcome and complete resolution of PI. None required surgical intervention.ConclusionPI in children who are not on chemotherapy or immunosuppressant appears to follow a benign course and is responsive to conservative management. In contrast to adults, portal venous gas and pneumoperitoneum do not predict the need for surgical intervention.

Published
2017

40. Adaptations to the current ECCO/ESPGHAN guidelines on the management of paediatric acute severe colitis in the context of the COVID-19 pandemic: a RAND appropriateness panel

Author

Hansen, Richard, Meade, Susanna, Beattie, R Mark, Auth, Marcus KH, Croft, Nick, Davies, Philip, Devadason, David, Doherty, Conor, Epstein, Jenny, Howarth, Lucy, Kiparissi, Fevronia, Muhammed, Rafeeq, Shivamurthy, Vinay, Spray, Christine, Stanton, Michael P, Torrente, Franco, Urs, Arun, Wilson, David, Irving, Peter M, Samaan, Mark, and Kammermeier, Jochen

Abstract

ObjectivePaediatric acute severe colitis (ASC) management during the novel SARS-CoV-2/COVID-19 pandemic is challenging due to reliance on immunosuppression and the potential for surgery. We aimed to provide COVID-19-specific guidance using the European Crohn’s and Colitis Organisation/European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines for comparison.DesignWe convened a RAND appropriateness panel comprising 14 paediatric gastroenterologists and paediatric experts in surgery, rheumatology, respiratory and infectious diseases. Panellists rated the appropriateness of interventions for ASC in the context of the COVID-19 pandemic. Results were discussed at a moderated meeting prior to a second survey.ResultsPanellists recommended patients with ASC have a SARS-CoV-2 swab and expedited biological screening on admission and should be isolated. A positive swab should trigger discussion with a COVID-19 specialist. Sigmoidoscopy was recommended prior to escalation to second-line therapy or colectomy. Methylprednisolone was considered appropriate first-line management in all, including those with symptomatic COVID-19. Thromboprophylaxis was also recommended in all. In patients requiring second-line therapy, infliximab was considered appropriate irrespective of SARS-CoV-2 status. Delaying colectomy due to SARS-CoV-2 infection was considered inappropriate. Corticosteroid tapering over 8–10 weeks was deemed appropriate for all. After successful corticosteroid rescue, thiopurine maintenance was rated appropriate in patients with negative SARS-CoV-2 swab and asymptomatic patients with positive swab but uncertain in symptomatic COVID-19.ConclusionOur COVID-19-specific adaptations to paediatric ASC guidelines using a RAND panel generally support existing recommendations, particularly the use of corticosteroids and escalation to infliximab, irrespective of SARS-CoV-2 status. Consideration of routine prophylactic anticoagulation was recommended.

Published
2021
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41. Azathioprine dosing and metabolite measurement in pediatric inflammatory bowel disease: does one size fit all?

Author

Walker, Rebecca, Kammermeier, Jochen, Vora, Rakesh, and Mutalib, Mohamed

Subjects
*INFLAMMATORY bowel diseases, *AZATHIOPRINE, *CROHN'S disease, *ULCERATIVE colitis, *ERYTHROCYTES
Abstract

Background Azathioprine is widely used for the maintenance of remission in children with inflammatory bowel disease (IBD). Measuring thiopurine metabolites 6-thioguanine (6-TGN) and 6-methyl-mercaptopurine (6-MMP) can aid in optimizing treatment and preventing toxicity. We report a proactive approach combining early metabolite measurements with IBD activity index to achieve optimal azathioprine dosing. Methods The reporting of azathioprine dosing, IBD activity indexes and thiopurine metabolites was evaluated retrospectively in 40 children with IBD. Additional treatments and the effect of azathioprine on blood counts were also examined. Results Forty children (40% female) with IBD (26 Crohn's disease, 12 ulcerative colitis, and 2 unclassified IBD), mean age 12.2±3.4 years, were included in the study. The mean azathioprine dose was 1.3±0.4 mg/kg; mean 6-TGN level was 280±151 pmol/8 × 108 red blood cells (RBC) and mean 6-MMP level 1022±1007 pmol/8 × 108 RBC. Disease activity index (Crohn's and ulcerative colitis, pediatric specific) at the time of metabolite measurement was 6.5±8. Twenty-eight children did not require azathioprine dose adjustment, while it was increased in 12. Data from children with azathioprine monotherapy were analyzed separately and the results were similar. Conclusion Timely measurement of thiopurine metabolites and clinical assessment can provide a powerful tool to optimize azathioprine dosing and reduce serious adverse effects in children with IBD. [ABSTRACT FROM AUTHOR]

Published
2019
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42. Phenotypic and Genotypic Characterisation of Inflammatory Bowel Disease Presenting Before the Age of 2 years

Author

Kammermeier, Jochen, primary, Dziubak, Robert, additional, Pescarin, Matilde, additional, Drury, Suzanne, additional, Godwin, Heather, additional, Reeve, Kate, additional, Chadokufa, Sibongile, additional, Huggett, Bonita, additional, Sider, Sara, additional, James, Chela, additional, Acton, Nikki, additional, Cernat, Elena, additional, Gasparetto, Marco, additional, Noble-Jamieson, Gabi, additional, Kiparissi, Fevronia, additional, Elawad, Mamoun, additional, Beales, Phil L., additional, Sebire, Neil J., additional, Gilmour, Kimberly, additional, Uhlig, Holm H., additional, Bacchelli, Chiara, additional, and Shah, Neil, additional

Published
2016
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45. The Diagnostic Approach to Monogenic Very Early Onset Inflammatory Bowel Disease

Author

Uhlig, Holm H., primary, Schwerd, Tobias, additional, Koletzko, Sibylle, additional, Shah, Neil, additional, Kammermeier, Jochen, additional, Elkadri, Abdul, additional, Ouahed, Jodie, additional, Wilson, David C., additional, Travis, Simon P., additional, Turner, Dan, additional, Klein, Christoph, additional, Snapper, Scott B., additional, and Muise, Aleixo M., additional

Published
2014
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46. Mutations in Tetratricopeptide Repeat Domain 7A Result in a Severe Form of Very Early Onset Inflammatory Bowel Disease

Author

Avitzur, Yaron, primary, Guo, Conghui, additional, Mastropaolo, Lucas A., additional, Bahrami, Ehsan, additional, Chen, Hannah, additional, Zhao, Zhen, additional, Elkadri, Abdul, additional, Dhillon, Sandeep, additional, Murchie, Ryan, additional, Fattouh, Ramzi, additional, Huynh, Hien, additional, Walker, Jennifer L., additional, Wales, Paul W., additional, Cutz, Ernest, additional, Kakuta, Yoichi, additional, Dudley, Joel, additional, Kammermeier, Jochen, additional, Powrie, Fiona, additional, Shah, Neil, additional, Walz, Christoph, additional, Nathrath, Michaela, additional, Kotlarz, Daniel, additional, Puchaka, Jacek, additional, Krieger, Jonathan R., additional, Racek, Tomas, additional, Kirchner, Thomas, additional, Walters, Thomas D., additional, Brumell, John H., additional, Griffiths, Anne M., additional, Rezaei, Nima, additional, Rashtian, Parisa, additional, Najafi, Mehri, additional, Monajemzadeh, Maryam, additional, Pelsue, Stephen, additional, McGovern, Dermot P.B., additional, Uhlig, Holm H., additional, Schadt, Eric, additional, Klein, Christoph, additional, Snapper, Scott B., additional, and Muise, Aleixo M., additional

Published
2014
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47. Allogeneic Stem Cell Transplant Offers Cure for Intractable Childhood Enteropathy

Author

Worth, Austen J.J., primary, Nademi, Zohreh, additional, Kammermeier, Jochen, additional, Bunn, Su, additional, Chiesa, Robert, additional, Cant, Andrew, additional, Hambleton, Sophie, additional, Shah, Neil, additional, Slatter, Mary, additional, Rao, Kanchan, additional, Gennery, Andrew, additional, Elawad, Mamoun, additional, Amrolia, Persis, additional, and Veys, Paul, additional

Published
2014
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48. Role of small-bowel endoscopy in the management of patients with inflammatory bowel disease: An international OMED-ECCO consensus

Author

Bourreille, Arnaud, Ignjatovic, Ana, Despott, Edward, Travis, Simon P L S., Colombel, Jean Frédéric, Van Gossum, André, Aabakken, Lars, Lo, Simon, Yamamoto, Hironori, Paulsen, Vemund, Loftus, Edward V., Reinisch, Walter, Swoger, Jason J.M., Eliakim, Rami, Leighton, Jonathan J.A., Mantzaris, Gerassimos G.J., Bisschops, Raf, Pennazio, Marco, Sanders, David D.P., Bar-Meir, Simon, Rondonotti, Emanuele, Bouhnik, Yoram, Moussata, Driffa, Ardizzone, Sandro, Panés, Julián, Seidman, Ernest, Heuschkel, Robert, Kammermeier, Jochen, Keuchel, Martin, Albert, Jörg Gerhard, Fortun, P.F. P.F., Radford-Smith, Graham, Bourreille, Arnaud, Ignjatovic, Ana, Despott, Edward, Travis, Simon P L S., Colombel, Jean Frédéric, Van Gossum, André, Aabakken, Lars, Lo, Simon, Yamamoto, Hironori, Paulsen, Vemund, Loftus, Edward V., Reinisch, Walter, Swoger, Jason J.M., Eliakim, Rami, Leighton, Jonathan J.A., Mantzaris, Gerassimos G.J., Bisschops, Raf, Pennazio, Marco, Sanders, David D.P., Bar-Meir, Simon, Rondonotti, Emanuele, Bouhnik, Yoram, Moussata, Driffa, Ardizzone, Sandro, Panés, Julián, Seidman, Ernest, Heuschkel, Robert, Kammermeier, Jochen, Keuchel, Martin, Albert, Jörg Gerhard, Fortun, P.F. P.F., and Radford-Smith, Graham

Abstract

Crohn's disease and ulcerative colitis are lifelong diseases seen predominantly in the developed countries of the world. Whereas ulcerative colitis is a chronic inflammatory condition causing diffuse and continuous mucosal inflammation of the colon, Crohn's disease is a heterogeneous entity comprised of several different phenotypes, but can affect the entire gastrointestinal tract. A change in diagnosis from Crohn's disease to ulcerative colitis during the first year of illness occurs in about 10%-15% of cases. Inflammatory bowel disease (IBD) restricted to the colon that cannot be characterized as either ulcerative colitis or Crohn's disease is termed IBD-unclassified (IBDU). The advent of capsule and both singleand double-balloon-assisted enteroscopy is revolutionizing small-bowel imaging and has major implications for diagnosis, classification, therapeutic decision making and outcomes in the management of IBD. The role of these investigations in the diagnosis and management of IBD, however, is unclear.This document sets out the current Consensus reached by a group of international experts in the fields of endoscopy and IBD at a meeting held in Brussels, 12-13th December 2008, organized jointly by the European Crohn's and Colitis Organisation (ECCO) and the Organisation Mondiale d'Endoscopie Digestive (OMED). The Consensus is grouped into seven sections: definitions and diagnosis; suspected Crohn's disease; established Crohn's disease; IBDU; ulcerative colitis (including ileal pouch-anal anastomosis [IPAA]); paediatric practice; and complications and unresolved questions.Consensus guideline statements are followed by comments on the evidence and opinion. Statements are intended to be read in context with qualifying comments and not read in isolation. © Georg Thieme Verlag KG Stuttgart New York., SCOPUS: re.j, info:eu-repo/semantics/published

Published
2009

49. Mo1979 Very Early Onset IBD: Phenotype-Genotype Characteristics and Treatment With Hematopoietic Stem Cell Transplantation

Author

Kammermeier, Jochen, primary, Howarth, Lucy, additional, Bacchelli, Chiara, additional, Drury, Suzanne, additional, Dyball, Bonita, additional, Chadokufa, Sibongile N., additional, Borrelli, Osvaldo, additional, Koeglmeier, Jutta, additional, Lindley, Keith, additional, Glocker, Erik, additional, Kiparissi, Fevronia, additional, Hill, Susan, additional, Lench, Nick J., additional, Sebire, Neil, additional, Veys, Paul, additional, Amrolia, Persis, additional, Thapar, Nikhil, additional, Elawad, Mamoun, additional, and Shah, Neil, additional

Published
2013
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50. Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Author

Serra, Eva Gonçalves, Schwerd, Tobias, Moutsianas, Loukas, Cavounidis, Athena, Fachal, Laura, Pandey, Sumeet, Kammermeier, Jochen, Croft, Nicholas M, Posovszky, Carsten, Rodrigues, Astor, Russell, Richard K, Barakat, Farah, Auth, Marcus K H, Heuschkel, Robert, Zilbauer, Matthias, Fyderek, Krzysztof, Braegger, Christian, Travis, Simon P, Satsangi, Jack, Parkes, Miles, Thapar, Nikhil, Ferry, Helen, Matte, Julie C, Gilmour, Kimberly C, Wedrychowicz, Andrzej, Sullivan, Peter, Moore, Carmel, Sambrook, Jennifer, Ouwehand, Willem, Roberts, David, Danesh, John, Baeumler, Toni A, Fulga, Tudor A, Karaminejadranjbar, Mohammad, Ahmed, Ahmed, Wilson, Rachel, Barrett, Jeffrey C, Elkadri, Abdul, Griffiths, Anne M, Snapper, Scott B, Shah, Neil, Muise, Aleixo M, Wilson, David C, Uhlig, Holm H, and Anderson, Carl A

Subjects
digestive system diseases, 3. Good health
Abstract

Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P

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