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2. Fourth mRNA COVID-19 vaccination in immunocompromised patients with haematological malignancies (COBRA KAI): a cohort study

Author

Kant, Iris M.J., Graas, Thecla, Toussaint, Belle, de Jong, Sterre, Darwesh, Shahan, Mahes, Sandjiv S., Kamminga, Dora, Koelewijn, Matthijs, Faber, Gino, Beaumont, Guus, Engel, Marije D., Pierie, R. Cheyenne N., Janssen, Suzanne R., van Dijkman, Edith, Heijmans, Jarom, Witte, Yara Y., Nahui Palomino, Rogers A., Omar, Said Z., Zweegman, Sonja, Kater, Arnon P., van den Vegt, Caya, Arends-Halbesma, Ilonka, de Pater, Emma, Dijkstra, Margriet J., Rots, Nynke Y., Rijnstra, Esther Siteur-van, de Rooij, Dennis M., Sanders, Rogier W., Poniman, Meliawati, Olijhoek, Wouter, van Rijswijk, Jacqueline, Beaumont, Tim, Çetinel, Lusia, Schellekens, Louis, den Hartogh, Yvonne M., Cloos, Jacqueline, Weijers, Suzanne S., Tonouh-Aajoud, Saïda, Avci, Selime, Roelandse-Koop, Elianne, Dik, Willem A., Hofsink, Quincy, Haggenburg, Sabine, Lissenberg-Witte, Birgit I., Broers, Annoek E.C., van Doesum, Jaap A., van Binnendijk, Rob S., den Hartog, Gerco, Bhoekhan, Michel S., Haverkate, Nienke J.E., van Meerloo, Johan, Burger, Judith A., Bouhuijs, Joey H., Smits, Gaby P., Wouters, Dorine, van Leeuwen, Ester M.M., Bontkes, Hetty J., Kootstra, Neeltje A., Vogels-Nooijen, Sandra, Rots, Nynke, van Beek, Josine, Heemskerk, Mirjam H.M., Groen, Kazimierz, van Meerten, Tom, Mutsaers, Pim G.N.J., van Gils, Marit J., Goorhuis, Abraham, Rutten, Caroline E., Hazenberg, Mette D., and Nijhof, Inger S.

Published
2023
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11. ATF2 and ATF7 Are Critical Mediators of Intestinal Epithelial Repair

Author

Meijer, Bartolomeus J., Giugliano, Francesca P., Baan, Bart, van der Meer, Jonathan H.M., Meisner, Sander, van Roest, Manon, Koelink, Pim J., de Boer, Ruben J., Jones, Nic, Breitwieser, Wolfgang, van der Wel, Nicole N., Wildenberg, Manon E., van den Brink, Gijs R., Heijmans, Jarom, and Muncan, Vanesa

Published
2020
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13. Epithelial argininosuccinate synthetase is dispensable for intestinal regeneration and tumorigenesis

Author

van der Meer, Jonathan H. M., de Boer, Ruben J., Meijer, Bartolomeus J., Smit, Wouter L., Vermeulen, Jacqueline L. M., Meisner, Sander, van Roest, Manon, Koelink, Pim J., Dekker, Evelien, Hakvoort, Theodorus B. M., Koster, Jan, Hawinkels, Lukas J. A. C., Heijmans, Jarom, Struijs, Eduard A., Boermeester, Marja A., van den Brink, Gijs R., and Muncan, Vanesa

Published
2021
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15. Blimp1 regulates the transition of neonatal to adult intestinal epithelium.

Author

Muncan, Vanesa, Heijmans, Jarom, Krasinski, Stephen D, Büller, Nikè V, Wildenberg, Manon E, Meisner, Sander, Radonjic, Marijana, Stapleton, Kelly A, Lamers, Wout H, Biemond, Izak, van den Bergh Weerman, Marius A, O'Carroll, Dónal, Hardwick, James C, Hommes, Daniel W, and van den Brink, Gijs R

Subjects
Intestinal Mucosa, Animals, Mice, Transgenic, Mice, Knockout, Mice, Transcription Factors, Gene Expression Regulation, Developmental, Female, Male, Positive Regulatory Domain I-Binding Factor 1, Gene Expression Regulation, Developmental, Knockout, Transgenic
Abstract

In many mammalian species, the intestinal epithelium undergoes major changes that allow a dietary transition from mother's milk to the adult diet at the end of the suckling period. These complex developmental changes are the result of a genetic programme intrinsic to the gut tube, but its regulators have not been identified. Here we show that transcriptional repressor B lymphocyte-induced maturation protein 1 (Blimp1) is highly expressed in the developing and postnatal intestinal epithelium until the suckling to weaning transition. Intestine-specific deletion of Blimp1 results in growth retardation and excessive neonatal mortality. Mutant mice lack all of the typical epithelial features of the suckling period and are born with features of an adult-like intestine. We conclude that the suckling to weaning transition is regulated by a single transcriptional repressor that delays epithelial maturation.

Published
2011

16. Intestinal tumorigenesis is not affected by progesterone signaling in rodent models.

Author

Heijmans, Jarom, Muncan, Vanesa, Jacobs, Rutger J, de Jonge-Muller, Eveline SM, Graven, Laura, Biemond, Izak, Ederveen, Antwan G, Groothuis, Patrick G, Mosselman, Sietse, Hardwick, James C, Hommes, Daniel W, and van den Brink, Gijs R

Subjects
Intestinal Mucosa, Colon, Intestine, Small, Animals, Mice, Rats, Intestinal Neoplasms, Cell Transformation, Neoplastic, Intestinal Polyposis, Disease Models, Animal, Progesterone, Receptors, Progesterone, Progestins, Immunohistochemistry, Signal Transduction, Cell Proliferation, Cell Transformation, Neoplastic, Disease Models, Animal, Intestine, Small, Receptors, General Science & Technology
Abstract

Clinical data suggest that progestins have chemopreventive properties in the development of colorectal cancer. We set out to examine a potential protective effect of progestins and progesterone signaling on colon cancer development. In normal and neoplastic intestinal tissue, we found that the progesterone receptor (PR) is not expressed. Expression was confined to sporadic mesenchymal cells. To analyze the influence of systemic progesterone receptor signaling, we crossed mice that lacked the progesterone receptor (PRKO) to the Apc(Min/+) mouse, a model for spontaneous intestinal polyposis. PRKO-Apc(Min/+) mice exhibited no change in polyp number, size or localization compared to Apc(Min/+). To examine effects of progestins on the intestinal epithelium that are independent of the PR, we treated mice with MPA. We found no effects of either progesterone or MPA on gross intestinal morphology or epithelial proliferation. Also, in rats treated with MPA, injection with the carcinogen azoxymethane did not result in a difference in the number or size of aberrant crypt foci, a surrogate end-point for adenoma development. We conclude that expression of the progesterone receptor is limited to cells in the intestinal mesenchyme. We did not observe any effect of progesterone receptor signaling or of progestin treatment in rodent models of intestinal tumorigenesis.

Published
2011

17. The role of EZH2 and DNA methylation in the silencing of the tumour suppressor RUNX3 in colorectal cancer.

Author

Kodach, Liudmila L, Jacobs, Rutger J, Heijmans, Jarom, van Noesel, Carel JM, Langers, Alexandra MJ, Verspaget, Hein W, Hommes, Daniel W, Offerhaus, G Johan A, van den Brink, Gijs R, and Hardwick, James CH

Subjects
Humans, Colorectal Neoplasms, DNA-Binding Proteins, Transcription Factors, RNA, Messenger, Blotting, Western, Immunoenzyme Techniques, Enzyme-Linked Immunosorbent Assay, Electrophoretic Mobility Shift Assay, Tissue Array Analysis, Chromatin Immunoprecipitation, Reverse Transcriptase Polymerase Chain Reaction, DNA Methylation, Gene Expression Regulation, Neoplastic, Gene Silencing, Regulatory Sequences, Nucleic Acid, Genes, Tumor Suppressor, Core Binding Factor Alpha 3 Subunit, Promoter Regions, Genetic, Enhancer of Zeste Homolog 2 Protein, Polycomb Repressive Complex 2, Blotting, Western, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Promoter Regions, Genetic, RNA, Messenger, Regulatory Sequences, Nucleic Acid, Oncology & Carcinogenesis, Oncology and Carcinogenesis
Abstract

In gastric cancer, a new epigenetic mechanism of tumour suppressor loss has been suggested where the histone methyltransferase enhancer of zeste homolog 2 (EZH2) is responsible for loss of expression of RUNX3. This is consistent with EZH2 upregulation in multiple cancer types being associated with poor prognosis. We investigated whether EZH2 influences the expression of RUNX3 in colorectal cancer (CRC) and whether this is independent of methylation. We determined protein and messenger RNA (mRNA) levels of EZH2 and RUNX3 and assessed RUNX3 methylation with methylation-specific polymerase chain reaction using 72 human CRCs and 8 CRC cell lines. We assessed the effect of efficient RNA interference-mediated knockdown of EZH2 on RUNX3 levels, cell viability and H3K27 trimethylation of the RUNX3 promoter using chromatin immunoprecipitation. Despite higher levels of EZH2 and lower levels of RUNX3 in CRC specimens in general, no inverse correlation between EZH2 and RUNX3 in paired samples was found arguing against a major role for histone methylation in silencing RUNX3 in CRC. Conversely, downregulation of RUNX3 mRNA in the same tumours was associated with RUNX3 DNA methylation (P < 0.05). In cell lines, knockdown of EZH2 removed the repressive chromatin marks from RUNX3 but did not result in RUNX3 re-expression. However, it prevented the re-silencing of RUNX3 after the removal of demethylating agents. In conclusion, DNA methylation is primarily responsible for the transcriptional silencing of RUNX3 in CRC, but EZH2 and histone methylation are necessary for its methylation-dependent re-silencing after the removal of demethylating agents. These results would predict that inhibitors of EZH2 and histone methylation would enhance the effects of demethylating agents in cancer therapy.

Published
2010

18. Grp78 is required for intestinal Kras-dependent glycolysis proliferation and adenomagenesis

Author

Spaan, Claudia N, primary, de Boer, Ruben J, additional, Smit, Wouter L, additional, van der Meer, Jonathan HM, additional, van Roest, Manon, additional, Vermeulen, Jacqueline LM, additional, Koelink, Pim J, additional, Becker, Marte AJ, additional, Go, Simei, additional, Silva, Joana, additional, Faller, William J, additional, van den Brink, Gijs R, additional, Muncan, Vanesa, additional, and Heijmans, Jarom, additional

Published
2023
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20. Hyperimmune Globulin for Severely Immunocompromised Patients Hospitalized With Coronavirus Disease 2019

Author

Huygens, Sammy, Hofsink, Quincy, Nijhof, Inger S., Goorhuis, Abraham, Kater, Arnon P., Te Boekhorst, Peter A.W., Swaneveld, Francis, Novotný, Věra M.J., Bogers, Susanne, Welkers, Matthijs R.A., Papageorgiou, Grigorios, Rijnders, Bart J., Heijmans, Jarom, Graduate School, Clinical Haematology, Infectious diseases, APH - Aging & Later Life, APH - Global Health, AII - Infectious diseases, Experimental Immunology, AII - Cancer immunology, CCA - Cancer biology and immunology, Medical Microbiology and Infection Prevention, General Internal Medicine, Internal Medicine, Hematology, Virology, and Epidemiology

Subjects
Infectious Diseases, SDG 3 - Good Health and Well-being, Immunology and Allergy, COVID-19, plasma-derived antibody therapy, anti-SARS-CoV-2 hyperimmune globulin, severely immunocompromised state, B-cell dysfunction
Abstract

Background The aim of this randomized, controlled trial is to determine whether antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin (COVIG) protects against severe coronavirus disease 2019 (COVID-19) in severely immunocompromised, hospitalized, COVID-19 patients. Methods Patients were randomly assigned to receive COVIG or intravenous immunoglobulin (IVIG) without SARS-CoV-2 antibodies. Results Severe COVID-19 was observed in 2 of 10 (20%) patients treated with COVIG compared to 7 of 8 (88%) in the IVIG control group (P = .015, Fisher’s exact test). Conclusions Antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin may be a valuable treatment in severely immunocompromised, hospitalized, COVID-19 patients and should be considered when no monoclonal antibody therapies are available.

Published
2023
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21. Fourth mRNA COVID-19 vaccination in immunocompromised patients with haematological malignancies (COBRA KAI): a cohort study

Author

Hofsink, Quincy, primary, Haggenburg, Sabine, additional, Lissenberg-Witte, Birgit I., additional, Broers, Annoek E.C., additional, van Doesum, Jaap A., additional, van Binnendijk, Rob S., additional, den Hartog, Gerco, additional, Bhoekhan, Michel S., additional, Haverkate, Nienke J.E., additional, van Meerloo, Johan, additional, Burger, Judith A., additional, Bouhuijs, Joey H., additional, Smits, Gaby P., additional, Wouters, Dorine, additional, van Leeuwen, Ester M.M., additional, Bontkes, Hetty J., additional, Kootstra, Neeltje A., additional, Vogels-Nooijen, Sandra, additional, Rots, Nynke, additional, van Beek, Josine, additional, Heemskerk, Mirjam H.M., additional, Groen, Kazimierz, additional, van Meerten, Tom, additional, Mutsaers, Pim G.N.J., additional, van Gils, Marit J., additional, Goorhuis, Abraham, additional, Rutten, Caroline E., additional, Hazenberg, Mette D., additional, Nijhof, Inger S., additional, Kant, Iris M.J., additional, Graas, Thecla, additional, Toussaint, Belle, additional, de Jong, Sterre, additional, Darwesh, Shahan, additional, Mahes, Sandjiv S., additional, Kamminga, Dora, additional, Koelewijn, Matthijs, additional, Faber, Gino, additional, Beaumont, Guus, additional, Engel, Marije D., additional, Pierie, R. Cheyenne N., additional, Janssen, Suzanne R., additional, van Dijkman, Edith, additional, Heijmans, Jarom, additional, Witte, Yara Y., additional, Nahui Palomino, Rogers A., additional, Omar, Said Z., additional, Zweegman, Sonja, additional, Kater, Arnon P., additional, van den Vegt, Caya, additional, Arends-Halbesma, Ilonka, additional, de Pater, Emma, additional, Dijkstra, Margriet J., additional, Rots, Nynke Y., additional, Rijnstra, Esther Siteur-van, additional, de Rooij, Dennis M., additional, Sanders, Rogier W., additional, Poniman, Meliawati, additional, Olijhoek, Wouter, additional, van Rijswijk, Jacqueline, additional, Beaumont, Tim, additional, Çetinel, Lusia, additional, Schellekens, Louis, additional, den Hartogh, Yvonne M., additional, Cloos, Jacqueline, additional, Weijers, Suzanne S., additional, Tonouh-Aajoud, Saïda, additional, Avci, Selime, additional, Roelandse-Koop, Elianne, additional, and Dik, Willem A., additional

Published
2023
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23. Hyperimmune Globulin for Severely Immunocompromised Patients Hospitalized With Coronavirus Disease 2019:A Randomized, Controlled Trial

Author

Huygens, Sammy, Hofsink, Quincy, Nijhof, Inger S., Goorhuis, Abraham, Kater, Arnon P., Te Boekhorst, Peter A.W., Swaneveld, Francis, Novotný, Věra M.J., Bogers, Susanne, Welkers, Matthijs R.A., Papageorgiou, Grigorios, Rijnders, Bart J., Heijmans, Jarom, Huygens, Sammy, Hofsink, Quincy, Nijhof, Inger S., Goorhuis, Abraham, Kater, Arnon P., Te Boekhorst, Peter A.W., Swaneveld, Francis, Novotný, Věra M.J., Bogers, Susanne, Welkers, Matthijs R.A., Papageorgiou, Grigorios, Rijnders, Bart J., and Heijmans, Jarom

Abstract

BACKGROUND: The aim of this randomized, controlled trial is to determine whether antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin (COVIG) protects against severe coronavirus disease 2019 (COVID-19) in severely immunocompromised, hospitalized, COVID-19 patients. METHODS: Patients were randomly assigned to receive COVIG or intravenous immunoglobulin (IVIG) without SARS-CoV-2 antibodies. RESULTS: Severe COVID-19 was observed in 2 of 10 (20%) patients treated with COVIG compared to 7 of 8 (88%) in the IVIG control group (P = .015, Fisher's exact test). CONCLUSIONS: Antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin may be a valuable treatment in severely immunocompromised, hospitalized, COVID-19 patients and should be considered when no monoclonal antibody therapies are available.

Published
2023

24. Stromal Indian Hedgehog Signaling Is Required for Intestinal Adenoma Formation in Mice

Author

Büller, Nikè V.J.A., Rosekrans, Sanne L., Metcalfe, Ciara, Heijmans, Jarom, van Dop, Willemijn A., Fessler, Evelyn, Jansen, Marnix, Ahn, Christina, Vermeulen, Jacqueline L.M., Westendorp, B. Florien, Robanus-Maandag, Els C., Offerhaus, G. Johan, Medema, Jan Paul, D’Haens, Geert R.A.M., Wildenberg, Manon E., de Sauvage, Frederic J., Muncan, Vanesa, and van den Brink, Gijs R.

Published
2015
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25. Comparison of Hidac Versus FLAG-IDA in the Treatment of Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Retrospective Study

Author

Tang, Man Wai, primary, van der Tuin, Deborah, additional, Aydin, Mesire, additional, Heijmans, Jarom, additional, van de Loosdrecht, Arjan A., additional, Meijer, Ellen, additional, Rutten, Caroline E., additional, Wondergem, Marielle, additional, Janssen, Jeroen J.W.M., additional, Donker, Marjolein, additional, Hazenberg, Mette D., additional, Zweegman, Sonja, additional, Biemond, Bart J., additional, de Leeuw, David C., additional, and Nur, Erfan, additional

Published
2022
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28. ER Stress Causes Rapid Loss of Intestinal Epithelial Stemness through Activation of the Unfolded Protein Response

Author

Heijmans, Jarom, van Lidth de Jeude, Jooske F., Koo, Bon-Kyoung, Rosekrans, Sanne L., Wielenga, Mattheus C.B., van de Wetering, Marc, Ferrante, Marc, Lee, Amy S., Onderwater, Jos J.M., Paton, James C., Paton, Adrienne W., Mommaas, A. Mieke, Kodach, Liudmila L., Hardwick, James C., Hommes, Daniël W., Clevers, Hans, Muncan, Vanesa, and van den Brink, Gijs R.

Published
2013
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29. Intestinal Tumorigenesis Initiated by Dedifferentiation and Acquisition of Stem-Cell-like Properties

Author

Schwitalla, Sarah, Fingerle, Alexander A., Cammareri, Patrizia, Nebelsiek, Tim, Göktuna, Serkan I., Ziegler, Paul K., Canli, Ozge, Heijmans, Jarom, Huels, David J., Moreaux, Guenievre, Rupec, Rudolf A., Gerhard, Markus, Schmid, Roland, Barker, Nick, Clevers, Hans, Lang, Roland, Neumann, Jens, Kirchner, Thomas, Taketo, Makoto M., van den Brink, Gijs R., Sansom, Owen J., Arkan, Melek C., and Greten, Florian R.

Published
2013
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30. Inactivation of Patched1 in Mice Leads to Development of Gastrointestinal Stromal-Like Tumors That Express Pdgfrα but Not Kit

Author

Pelczar, Penelope, Zibat, Arne, van Dop, Willemijn A., Heijmans, Jarom, Bleckmann, Annalen, Gruber, Wolfgang, Nitzki, Frauke, Uhmann, Anja, Guijarro, Maria V., Hernando, Eva, Dittmann, Kai, Wienands, Jürgen, Dressel, Ralf, Wojnowski, Leszek, Binder, Claudia, Taguchi, Takahiro, Beissbarth, Tim, Hogendoorn, Pancras C.W., Antonescu, Cristina R., Rubin, Brian P., Schulz–Schaeffer, Walter, Aberger, Fritz, van den Brink, Gijs R., and Hahn, Heidi

Published
2013
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31. Third-generation cephalosporin resistant gram-negative bacteraemia in patients with haematological malignancy; an 11-year multi-centre retrospective study

Author

de la Court, Jara R, Woudt, Sjoukje H S, Schoffelen, Annelot F, Heijmans, Jarom, de Jonge, Nick A, van der Bruggen, Tjomme, Bomers, Marije K, Lambregts, Merel M C, Schade, Rogier P, and Sigaloff, Kim C E

Subjects
Third-generation-cephalosporin resistance, Febrile neutropenia, Colonization, Resistance surveillance, Antimicrobial resistance, Empirical antibiotic therapy
Abstract

Objectives Among patients with haematological malignancy, bacteraemia is a common complication during chemotherapy-induced neutropenia. Resistance of gram-negative pathogens to third-generation cephalosporins is increasing. We aimed to assess the distribution of pathogens causing bacteraemia in patients with haematological malignancy, and the proportion of 3GC-R GNB bacteraemia that was preceded by 3GC-R GNB colonization. Methods Using 11 years of data (2008–2018) from the Dutch national antimicrobial resistance surveillance system, we assessed the prevalence of third-generation cephalosporin resistant Gram-negative bacteria (3GC-R GNB) in episodes of bacteraemia, and the proportion of 3GC-R GNB bacteraemia that was preceded by 3GC-R GNB colonization (identified using surveillance cultures) in the year before. Results We included 3,887 patients, representing 4,142 episodes of bacteraemia. GNB were identified in 715/4,142 (17.3%), of which 221 (30.9%) were 3GC-R GNB. In (106/139) 76.2% of patients with a 3GC-R GNB bacteraemia and available GNB surveillance cultures in the preceding year, 3GC-R GNB colonization had been previously identified. Conclusions This multi-centre study shows that in patients with haematological malignancy, the majority of 3GC-R GNB bacteraemia is preceded by 3GC-R GNB colonization. Prospective clinical studies are needed to assess the safety and benefits of surveillance-culture guided empirical therapy to restrict the empirical use of carbapenems in this population.

Published
2022
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33. Guidance of empirical antimicrobial therapy by surveillance cultures in high-risk neutropenic patients: a retrospective cohort study

Author

MMB Medische Staf, Infection & Immunity, de la Court, Jara R, Heijmans, Jarom, Huynh, Jennifer, Sieswerda, Elske, de Jonge, Nick A, van Dijk, Karin, Sigaloff, Kim C E, Schade, Rogier P, MMB Medische Staf, Infection & Immunity, de la Court, Jara R, Heijmans, Jarom, Huynh, Jennifer, Sieswerda, Elske, de Jonge, Nick A, van Dijk, Karin, Sigaloff, Kim C E, and Schade, Rogier P

Published
2022

34. Loss of Indian Hedgehog Activates Multiple Aspects of a Wound Healing Response in the Mouse Intestine

Author

van Dop, Willemijn A., Heijmans, Jarom, Büller, Nikè V.J.A., Snoek, Susanne A., Rosekrans, Sanne L., Wassenberg, Elisabeth A., van den Bergh Weerman, Marius A., Lanske, Beate, Clarke, Alan R., Winton, Douglas J., Wijgerde, Mark, Offerhaus, G. Johan, Hommes, Daan W., Hardwick, James C., de Jonge, Wouter J., Biemond, Izak, and van den Brink, Gijs R.

Published
2010
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37. Risk of Severe Sars-Cov-2 Infections in COVID-19 Vaccinated Individuals with Hematologic Malignancies (SAVE HEM): A Nationwide Cohort Study in the Netherlands

Author

Hofsink, Quincy, Haggenburg, Sabine, Lissenberg-Witte, Birgit I., Goorhuis, Abraham, Hazenberg, Mette D., Rutten, Caroline E., Zweegman, Sonja, Kemmeren, Jeanet, de Keizer, Nicolette F., Huijgens, Peter C., Dinmohamed, Avinash G., van den Hof, Susan, de Gier, Brechje, Knol, Mirjam, Hahné, Susan, Heijmans, Jarom, and Nijhof, Inger S.

Published
2023
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39. Sirolimus for the treatment of polyposis of the rectal remnant and ileal pouch in four patients with familial adenomatous polyposis: a pilot study

Author

Roos, Victorine H, primary, Meijer, Bartolomeus J, additional, Kallenberg, Frank G J, additional, Bastiaansen, Barbara A J, additional, Koens, Lianne, additional, Bemelman, Frederike J, additional, Bossuyt, Patrick M M, additional, Heijmans, Jarom, additional, van den Brink, Gijs, additional, and Dekker, Evelien, additional

Published
2020
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40. Diagnosing COVID-19 pneumonia in a pandemic setting: Lung Ultrasound versus CT (LUVCT) – a multicentre, prospective, observational study

Author

Lieveld, Arthur W.E., primary, Kok, Bram, additional, Schuit, Frederik H., additional, Azijli, Kaoutar, additional, Heijmans, Jarom, additional, van Laarhoven, Arjan, additional, Assman, Natascha L., additional, Kootte, Ruud S., additional, Olgers, Tycho J., additional, Nanayakkara, Prabath W.B., additional, and Bosch, Frank H., additional

Published
2020
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43. Epithelial endoplasmic reticulum stress orchestrates a protective IgA response

Author

Grootjans, Joep, Krupka, Niklas, Hosomi, Shuhei, Matute, Juan D, Hanley, Thomas, Saveljeva, Svetlana, Gensollen, Thomas, Heijmans, Jarom, Li, Hai, Limenitakis, Julien P, Ganal-Vonarburg, Stephanie C, Suo, Shengbao, Luoma, Adrienne M, Shimodaira, Yosuke, Duan, Jinzhi, Shih, David Q, Conner, Margaret E, Glickman, Jonathan N, Fuhler, Gwenny M, Palm, Noah W, de Zoete, Marcel R, van der Woude, C Janneke, Yuan, Guo-Cheng, Wucherpfennig, Kai W, Targan, Stephan R, Rosenstiel, Philip, Flavell, Richard A, McCoy, Kathy D, Macpherson, Andrew J, Kaser, Arthur, Blumberg, Richard S, Grootjans, Joep, Krupka, Niklas, Hosomi, Shuhei, Matute, Juan D, Hanley, Thomas, Saveljeva, Svetlana, Gensollen, Thomas, Heijmans, Jarom, Li, Hai, Limenitakis, Julien P, Ganal-Vonarburg, Stephanie C, Suo, Shengbao, Luoma, Adrienne M, Shimodaira, Yosuke, Duan, Jinzhi, Shih, David Q, Conner, Margaret E, Glickman, Jonathan N, Fuhler, Gwenny M, Palm, Noah W, de Zoete, Marcel R, van der Woude, C Janneke, Yuan, Guo-Cheng, Wucherpfennig, Kai W, Targan, Stephan R, Rosenstiel, Philip, Flavell, Richard A, McCoy, Kathy D, Macpherson, Andrew J, Kaser, Arthur, and Blumberg, Richard S

Abstract

Immunoglobulin A (IgA) is the major secretory immunoglobulin isotype found at mucosal surfaces, where it regulates microbial commensalism and excludes luminal factors from contacting intestinal epithelial cells (IECs). IgA is induced by both T cell-dependent and -independent (TI) pathways. However, little is known about TI regulation. We report that IEC endoplasmic reticulum (ER) stress induces a polyreactive IgA response, which is protective against enteric inflammation. IEC ER stress causes TI and microbiota-independent expansion and activation of peritoneal B1b cells, which culminates in increased lamina propria and luminal IgA. Increased numbers of IgA-producing plasma cells were observed in healthy humans with defective autophagy, who are known to exhibit IEC ER stress. Upon ER stress, IECs communicate signals to the peritoneum that induce a barrier-protective TI IgA response.

Published
2019

44. Epithelial endoplasmic reticulum stress orchestrates a protective IgA response

Author

dI&I I&I-2, LS Infectiebiologie (Bacteriologie), Grootjans, Joep, Krupka, Niklas, Hosomi, Shuhei, Matute, Juan D, Hanley, Thomas, Saveljeva, Svetlana, Gensollen, Thomas, Heijmans, Jarom, Li, Hai, Limenitakis, Julien P, Ganal-Vonarburg, Stephanie C, Suo, Shengbao, Luoma, Adrienne M, Shimodaira, Yosuke, Duan, Jinzhi, Shih, David Q, Conner, Margaret E, Glickman, Jonathan N, Fuhler, Gwenny M, Palm, Noah W, de Zoete, Marcel R, van der Woude, C Janneke, Yuan, Guo-Cheng, Wucherpfennig, Kai W, Targan, Stephan R, Rosenstiel, Philip, Flavell, Richard A, McCoy, Kathy D, Macpherson, Andrew J, Kaser, Arthur, Blumberg, Richard S, dI&I I&I-2, LS Infectiebiologie (Bacteriologie), Grootjans, Joep, Krupka, Niklas, Hosomi, Shuhei, Matute, Juan D, Hanley, Thomas, Saveljeva, Svetlana, Gensollen, Thomas, Heijmans, Jarom, Li, Hai, Limenitakis, Julien P, Ganal-Vonarburg, Stephanie C, Suo, Shengbao, Luoma, Adrienne M, Shimodaira, Yosuke, Duan, Jinzhi, Shih, David Q, Conner, Margaret E, Glickman, Jonathan N, Fuhler, Gwenny M, Palm, Noah W, de Zoete, Marcel R, van der Woude, C Janneke, Yuan, Guo-Cheng, Wucherpfennig, Kai W, Targan, Stephan R, Rosenstiel, Philip, Flavell, Richard A, McCoy, Kathy D, Macpherson, Andrew J, Kaser, Arthur, and Blumberg, Richard S

Published
2019

45. Heterozygosity of Chaperone Grp78 Reduces Intestinal Stem Cell Regeneration Potential and Protects against Adenoma Formation

Author

van Lidth de Jeude, Jooske F., primary, Spaan, Claudia N., additional, Meijer, Bartolomeus J., additional, Smit, Wouter L., additional, Soeratram, Tanya T.D., additional, Wielenga, Mattheus C.B., additional, Westendorp, B. Florien, additional, Lee, Amy S., additional, Meisner, Sander, additional, Vermeulen, Jacqueline L.M., additional, Wildenberg, Manon E., additional, van den Brink, Gijs R., additional, Muncan, Vanesa, additional, and Heijmans, Jarom, additional

Published
2018
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46. Calnexin Depletion by Endoplasmic Reticulum Stress During Cholestasis Inhibits the Na + ‐Taurocholate Cotransporting Polypeptide

Author

Robin, Marion J.D., primary, Appelman, Monique D., additional, Vos, Harmjan R., additional, van Es, Robert M., additional, Paton, James C., additional, Paton, Adrienne W., additional, Burgering, Boudewijn, additional, Fickert, Peter, additional, Heijmans, Jarom, additional, and van de Graaf, Stan F.J., additional

Published
2018
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50. Calnexin Depletion by Endoplasmic Reticulum Stress During Cholestasis Inhibits the Na+‐Taurocholate Cotransporting Polypeptide.

Author

Robin, Marion J.D., Appelman, Monique D., Vos, Harmjan R., van Es, Robert M., Paton, James C., Paton, Adrienne W., Burgering, Boudewijn, Fickert, Peter, Heijmans, Jarom, and van de Graaf, Stan F.J.

Abstract

Cholestasis‐induced accumulation of bile acids in the liver leads to farnesoid X receptor (FXR)‐mediated transcriptional down‐regulation of the bile acid importer Na+‐taurocholate cotransporting protein (NTCP) and to induction of endoplasmic reticulum (ER) stress. However, whether ER stress affects bile acid uptake is largely unknown. Here, we investigated the role of ER stress on the regulation and function of the bile acid transporter NTCP. ER stress was induced using thapsigargin or subtilase cytotoxin in human osteosarcoma (U2OS) and human hepatocellular carcinoma (HepG2) cells stably expressing NTCP. Cellular bile acid uptake was determined using radiolabeled taurocholate (TCA). NTCP plasma membrane expression was determined by cell surface biotinylation. Mice received a single injection of thapsigargin, and effects of ER stress on NTCP messenger RNA (mRNA) and protein were measured by reverse‐transcription polymerase chain reaction (RT‐PCR) and western blot analysis. Effects of cholestasis on NTCP and ER stress were assessed in response to 3, 5‐diethoxycarbonyl‐1, 4‐dihydrocollidine (DDC) feeding or bile duct ligation in FXR–/– mice after 7 or 3 days, respectively. Novel NTCP‐interacting proteins were identified by mass spectrometry (MS), interaction verified, and assessed by co‐immunoprecipitation and TCA uptake for functional relevance in relation to ER stress. ER stress induction strongly reduced NTCP protein expression, plasma membrane abundance, and NTCP‐mediated bile acid uptake. This was not controlled by FXR or through a single unfolded protein response (UPR) pathway but mainly depended on the interaction of NTCP with calnexin, an ER chaperone. In mice, expression of both NTCP and calnexin was reduced by thapsigargin or cholestasis‐induced ER stress. Calnexin down‐regulation in vitro recapitulated the effect of ER stress on NTCP. Conclusion: ER stress‐induced down‐regulation of calnexin provides an additional mechanism to dampen NTCP‐mediated bile acid uptake and protect hepatocytes against bile acid overload during cholestasis. [ABSTRACT FROM AUTHOR]

Published
2018
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