Search

Your search keyword '"Kuijpers, T.W."' showing total 333 results
Start Over Author "Kuijpers, T.W."
333 results on '"Kuijpers, T.W."'

1. Host gene expression signatures to identify infection type and organ dysfunction in children evaluated for sepsis: a multicentre cohort study

Author

Levin, Michael, Coin, Lachlan, Gormley, Stuart, Hamilton, Shea, Hoggart, Clive, Kaforou, Myrsini, Sancho-Shimizu, Vanessa, Wright, Victoria, Abdulla, Amina, Agapow, Paul, Bartlett, Maeve, Eleftherohorinou, Hariklia, Galassini, Rachel, Inwald, David, Mashbat, Meg, Menikou, Stephanie, Mustafa, Sobia, Nadel, Simon, Rahman, Rahmeen, Shailes, Hannah, Thakker, Clare, Bokhandi, S., Power, Sue, Barham, Heather, Pathan, N., Ridout, Jenna, White, Deborah, Thurston, Sarah, Faust, S., Patel, S., McCorkell, Jenni, Davies, P., Crate, Lindsey, Navarra, Helen, Carter, Stephanie, Ramaiah, R., Patel, Rekha, Tuffrey, Catherine, Gribbin, Andrew, McCready, Sharon, Peters, Mark, Hardy, Katie, Standing, Fran, O'Neill, Lauren, Abelake, Eugenia, Deep, Akash, Nsirim, Eniola, Pollard, Andrew, Willis, Louise, Young, Zoe, Royad, C., White, Sonia, Fortune, Peter-Marc, Hudnott, Phil, Martinón-Torres, Federico, Salas, Antonio, Álvez González, Fernando, Barral-Arca, Ruth, Cebey-López, Miriam, Curras-Tuala, María José, García, Natalia, García Vicente, Luisa, Gómez-Carballa, Alberto, Gómez Rial, Jose, Grela Beiroa, Andrea, Justicia Grande, Antonio, Leboráns Iglesias, Pilar, Martínez Santos, Alba Elena, Martinón-Torres, Nazareth, Martinón Sánchez, José María, Morillo Gutiérrez, Beatriz, Mosquera Pérez, Belén, Obando Pacheco, Pablo, Pardo-Seco, Jacobo, Pischedda, Sara, Rivero-Calle, Irene, Rodríguez-Tenreiro, Carmen, Redondo-Collazo, Lorenzo, Salas Ellacuriaga, Antonio, Fernández, Sonia Serén, del Sol Porto Silva, María, Vega, Ana, Vilanova Trillo, Lucía, Reyes, Susana Beatriz, Cruz León León, María, Navarro Mingorance, Álvaro, Gabaldó Barrio, Xavier, Oñate Vergara, Eider, Concha Torre, Andrés, Vivanco, Ana, Fernández, Reyes, Giménez Sánchez, Francisco, Sánchez Forte, Miguel, Rojo, Pablo, Contreras, J. Ruiz, Palacios, Alba, Epalza Ibarrondo, Cristina, Fernández Cooke, Elizabeth, Navarro, Marisa, Álvarez Álvarez, Cristina, José Lozano, María, Carreras, Eduardo, Brió Sanagustín, Sonia, Neth, Olaf, Martínez Padilla, Mª del Carmen, Prieto Tato, Luis Manuel, Guillén, Sara, Fernández Silveira, Laura, Moreno, David, de Groot, R., Tutu van Furth, A.M., van der Flier, M., Boeddha, N.P., Driessen, G.J.A., Emonts, M., Hazelzet, J.A., Kuijpers, T.W., Pajkrt, D., Sanders, E.A.M., van de Beek, D., van der Ende, A., Philipsen, H.L.A., Adeel, A.O.A., Breukels, M.A., Brinkman, D.M.C., de Korte, C.C.M.M., de Vries, E., de Waal, W.J., Dekkers, R., Dings-Lammertink, A., Doedens, R.A., Donker, A.E., Dousma, M., Faber, T.E., Gerrits, G.P.J.M., Gerver, J.A.M., Heidema, J., Homan-van der Veen, J., Jacobs, M.A.M., Jansen, N.J.G., Kawczynski, P., Klucovska, K., Kneyber, M.C.J., Koopman-Keemink, Y., Langenhorst, V.J., Leusink, J., Loza, B.F., Merth, I.T., Miedema, C.J., Neeleman, C., Noordzij, J.G., Obihara, C.C., van Overbeek- van Gils, A.L.T., Poortman, G.H., Potgieter, S.T., Potjewijd, J., Rosias, P.P.R., Sprong, T., ten Tussher, G.W., Thio, B.J., Tramper-Stranders, G.A., van Deuren, M., van der Meer, H., van Kuppevelt, A.J.M., van Wermeskerken, A.M., Verwijs, W.A., Wolfs, T.F.W., Schlapbach, Luregn J., Agyeman, Philipp, Aebi, Christoph, Giannoni, Eric, Stocker, Martin, Posfay-Barbe, Klara M., Heininger, Ulrich, Bernhard-Stirnemann, Sara, Niederer-Loher, Anita, Kahlert, Christian, Hasters, Paul, Relly, Christa, Baer, Walter, Berger, Christoph, Carrol, Enitan D., Paulus, Stéphane, Frederick, Hannah, Jennings, Rebecca, Johnston, Joanne, Kenwright, Rhian, Fink, Colin G, Pinnock, Elli, Emonts, Marieke, Agbeko, Rachel, Anderson, Suzanne, Secka, Fatou, Bojang, Kalifa, Sarr, Isatou, Kebbeh, Ngange, Sey, Gibbi, Saidykhan, Momodou, Cole, Fatoumata, Thomas, Gilleh, Antonio, Martin, Zenz, Werner, Kohlfürst, Daniela S., Binder, Alexander, Schweintzger, Nina A., Sagmeister, Manfred, Baumgart, Hinrich, Baumgartner, Markus, Behrends, Uta, Biebl, Ariane, Birnbacher, Robert, Blanke, Jan-Gerd, Boelke, Carsten, Breuling, Kai, Brunner, Jürgen, Buller, Maria, Dahlem, Peter, Dietrich, Beate, Eber, Ernst, Elias, Johannes, Emhofer, Josef, Etschmaier, Rosa, Farr, Sebastian, Girtler, Ylenia, Grigorow, Irina, Heimann, Konrad, Ihm, Ulrike, Jaros, Zdenek, Kalhoff, Hermann, Kaulfersch, Wilhelm, Kemen, Christoph, Klocker, Nina, Köster, Bernhard, Kohlmaier, Benno, Komini, Eleni, Kramer, Lydia, Neubert, Antje, Ortner, Daniel, Pescollderungg, Lydia, Pfurtscheller, Klaus, Reiter, Karl, Ristic, Goran, Rödl, Siegfried, Sellner, Andrea, Sonnleitner, Astrid, Sperl, Matthias, Stelzl, Wolfgang, Till, Holger, Trobisch, Andreas, Vierzig, Anne, Vogel, Ulrich, Weingarten, Christina, Welke, Stefanie, Wimmer, Andreas, Wintergerst, Uwe, Wüller, Daniel, Zaunschirm, Andrew, Ziuraite, Ieva, Žukovskaja, Veslava, Hibberd, Martin L., Davila, Sonia, Delany, Isabel, Schlapbach, Luregn J, Raman, Sainath, Sharp, Nathalie, Phillips, Natalie, Irwin, Adam, Balch, Ross, Harley, Amanda, Johnson, Kerry, Sever, Zoe, George, Shane, Grimwood, Keith, Snelling, Peter J, Chavan, Arjun, Kitcatt, Eleanor, Lawton, Luke, Hempenstall, Allison, Pilot, Pelista, Gibbons, Kristen S, Le Marsney, Renate, Blumenthal, Antje, Ganesamoorthy, Devika, Pardo, Carolyn, Kling, Jessica, McPherson, Stephen, MacDonald, Anna D, Bialasiewicz, Seweryn, Pham, Trang, Wilson, Clare, Sharp, Natalie, Kling, Jessica C, McPherson, Stephen J, Herberg, Jethro A, and Coin, Lachlan J M

Published
2024
Full Text
View/download PDF

3. 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
Full Text
View/download PDF

6. Host gene expression signatures to identify infection type and organ dysfunction in children evaluated for sepsis: a multicentre cohort study

Author

Schlapbach, Luregn J, Ganesamoorthy, Devika, Wilson, Clare, Raman, Sainath, George, Shane, Snelling, Peter J, Phillips, Natalie, Irwin, Adam, Sharp, Natalie, Le Marsney, Renate, Chavan, Arjun, Hempenstall, Allison, Bialasiewicz, Seweryn, MacDonald, Anna D, Grimwood, Keith, Kling, Jessica C, McPherson, Stephen J, Blumenthal, Antje, Kaforou, Myrsini, Levin, Michael, Herberg, Jethro A, Gibbons, Kristen S, Coin, Lachlan J M, Levin, Michael, Coin, Lachlan, Gormley, Stuart, Hamilton, Shea, Hoggart, Clive, Kaforou, Myrsini, Sancho-Shimizu, Vanessa, Wright, Victoria, Abdulla, Amina, Agapow, Paul, Bartlett, Maeve, Eleftherohorinou, Hariklia, Galassini, Rachel, Inwald, David, Mashbat, Meg, Menikou, Stephanie, Mustafa, Sobia, Nadel, Simon, Rahman, Rahmeen, Shailes, Hannah, Thakker, Clare, Bokhandi, S., Power, Sue, Barham, Heather, Pathan, N., Ridout, Jenna, White, Deborah, Thurston, Sarah, Faust, S., Patel, S., McCorkell, Jenni, Davies, P., Crate, Lindsey, Navarra, Helen, Carter, Stephanie, Ramaiah, R., Patel, Rekha, Tuffrey, Catherine, Gribbin, Andrew, McCready, Sharon, Peters, Mark, Hardy, Katie, Standing, Fran, O'Neill, Lauren, Abelake, Eugenia, Deep, Akash, Nsirim, Eniola, Pollard, Andrew, Willis, Louise, Young, Zoe, Royad, C., White, Sonia, Fortune, Peter-Marc, Hudnott, Phil, Martinón-Torres, Federico, Salas, Antonio, Álvez González, Fernando, Barral-Arca, Ruth, Cebey-López, Miriam, Curras-Tuala, María José, García, Natalia, García Vicente, Luisa, Gómez-Carballa, Alberto, Gómez Rial, Jose, Grela Beiroa, Andrea, Justicia Grande, Antonio, Leboráns Iglesias, Pilar, Martínez Santos, Alba Elena, Martinón-Torres, Nazareth, Martinón Sánchez, José María, Morillo Gutiérrez, Beatriz, Mosquera Pérez, Belén, Obando Pacheco, Pablo, Pardo-Seco, Jacobo, Pischedda, Sara, Rivero-Calle, Irene, Rodríguez-Tenreiro, Carmen, Redondo-Collazo, Lorenzo, Salas Ellacuriaga, Antonio, Fernández, Sonia Serén, del Sol Porto Silva, María, Vega, Ana, Vilanova Trillo, Lucía, Reyes, Susana Beatriz, Cruz León León, María, Navarro Mingorance, Álvaro, Gabaldó Barrio, Xavier, Oñate Vergara, Eider, Concha Torre, Andrés, Vivanco, Ana, Fernández, Reyes, Giménez Sánchez, Francisco, Sánchez Forte, Miguel, Rojo, Pablo, Contreras, J. Ruiz, Palacios, Alba, Epalza Ibarrondo, Cristina, Fernández Cooke, Elizabeth, Navarro, Marisa, Álvarez Álvarez, Cristina, José Lozano, María, Carreras, Eduardo, Brió Sanagustín, Sonia, Neth, Olaf, Martínez Padilla, Mª del Carmen, Prieto Tato, Luis Manuel, Guillén, Sara, Fernández Silveira, Laura, Moreno, David, de Groot, R., Tutu van Furth, A.M., van der Flier, M., Boeddha, N.P., Driessen, G.J.A., Emonts, M., Hazelzet, J.A., Kuijpers, T.W., Pajkrt, D., Sanders, E.A.M., van de Beek, D., van der Ende, A., Philipsen, H.L.A., Adeel, A.O.A., Breukels, M.A., Brinkman, D.M.C., de Korte, C.C.M.M., de Vries, E., de Waal, W.J., Dekkers, R., Dings-Lammertink, A., Doedens, R.A., Donker, A.E., Dousma, M., Faber, T.E., Gerrits, G.P.J.M., Gerver, J.A.M., Heidema, J., Homan-van der Veen, J., Jacobs, M.A.M., Jansen, N.J.G., Kawczynski, P., Klucovska, K., Kneyber, M.C.J., Koopman-Keemink, Y., Langenhorst, V.J., Leusink, J., Loza, B.F., Merth, I.T., Miedema, C.J., Neeleman, C., Noordzij, J.G., Obihara, C.C., van Overbeek- van Gils, A.L.T., Poortman, G.H., Potgieter, S.T., Potjewijd, J., Rosias, P.P.R., Sprong, T., ten Tussher, G.W., Thio, B.J., Tramper-Stranders, G.A., van Deuren, M., van der Meer, H., van Kuppevelt, A.J.M., van Wermeskerken, A.M., Verwijs, W.A., Wolfs, T.F.W., Schlapbach, Luregn J., Agyeman, Philipp, Aebi, Christoph, Giannoni, Eric, Stocker, Martin, Posfay-Barbe, Klara M., Heininger, Ulrich, Bernhard-Stirnemann, Sara, Niederer-Loher, Anita, Kahlert, Christian, Hasters, Paul, Relly, Christa, Baer, Walter, Berger, Christoph, Carrol, Enitan D., Paulus, Stéphane, Frederick, Hannah, Jennings, Rebecca, Johnston, Joanne, Kenwright, Rhian, Fink, Colin G, Pinnock, Elli, Emonts, Marieke, Agbeko, Rachel, Anderson, Suzanne, Secka, Fatou, Bojang, Kalifa, Sarr, Isatou, Kebbeh, Ngange, Sey, Gibbi, Saidykhan, Momodou, Cole, Fatoumata, Thomas, Gilleh, Antonio, Martin, Zenz, Werner, Kohlfürst, Daniela S., Binder, Alexander, Schweintzger, Nina A., Sagmeister, Manfred, Baumgart, Hinrich, Baumgartner, Markus, Behrends, Uta, Biebl, Ariane, Birnbacher, Robert, Blanke, Jan-Gerd, Boelke, Carsten, Breuling, Kai, Brunner, Jürgen, Buller, Maria, Dahlem, Peter, Dietrich, Beate, Eber, Ernst, Elias, Johannes, Emhofer, Josef, Etschmaier, Rosa, Farr, Sebastian, Girtler, Ylenia, Grigorow, Irina, Heimann, Konrad, Ihm, Ulrike, Jaros, Zdenek, Kalhoff, Hermann, Kaulfersch, Wilhelm, Kemen, Christoph, Klocker, Nina, Köster, Bernhard, Kohlmaier, Benno, Komini, Eleni, Kramer, Lydia, Neubert, Antje, Ortner, Daniel, Pescollderungg, Lydia, Pfurtscheller, Klaus, Reiter, Karl, Ristic, Goran, Rödl, Siegfried, Sellner, Andrea, Sonnleitner, Astrid, Sperl, Matthias, Stelzl, Wolfgang, Till, Holger, Trobisch, Andreas, Vierzig, Anne, Vogel, Ulrich, Weingarten, Christina, Welke, Stefanie, Wimmer, Andreas, Wintergerst, Uwe, Wüller, Daniel, Zaunschirm, Andrew, Ziuraite, Ieva, Žukovskaja, Veslava, Hibberd, Martin L., Davila, Sonia, Delany, Isabel, Schlapbach, Luregn J, Raman, Sainath, Sharp, Nathalie, Phillips, Natalie, Irwin, Adam, Balch, Ross, Harley, Amanda, Johnson, Kerry, Sever, Zoe, George, Shane, Grimwood, Keith, Snelling, Peter J, Chavan, Arjun, Kitcatt, Eleanor, Lawton, Luke, Hempenstall, Allison, Pilot, Pelista, Gibbons, Kristen S, Le Marsney, Renate, Blumenthal, Antje, Ganesamoorthy, Devika, Pardo, Carolyn, Kling, Jessica, McPherson, Stephen, MacDonald, Anna D, Bialasiewicz, Seweryn, Pham, Trang, and Coin, Lachlan

Abstract

Sepsis is defined as dysregulated host response to infection that leads to life-threatening organ dysfunction. Biomarkers characterising the dysregulated host response in sepsis are lacking. We aimed to develop host gene expression signatures to predict organ dysfunction in children with bacterial or viral infection.

Published
2024
Full Text
View/download PDF

7. Febrile illness in high-risk children: a prospective, international observational study.

Author

Velden, F.J.S. van der, Vries, G de, Martin, A., Lim, E., Both, U. von, Kolberg, L., Carrol, E.D., Khanijau, A., Herberg, Jethro A., De, T., Galassini, R., Kuijpers, T.W., Martinón-Torres, F., Rivero-Calle, I., Vermont, C.L., Hagedoorn, N.N., Pokorn, M., Pollard, A.J., Schlapbach, L.J., Tsolia, M., Elefhteriou, I., Yeung, S., Zavadska, D., Fink, C., Voice, M., Zenz, W., Kohlmaier, B., Agyeman, P.K.A., Usuf, E., Secka, F., Groot, R. de, Levin, M., Flier, M. van der, Emonts, M., Velden, F.J.S. van der, Vries, G de, Martin, A., Lim, E., Both, U. von, Kolberg, L., Carrol, E.D., Khanijau, A., Herberg, Jethro A., De, T., Galassini, R., Kuijpers, T.W., Martinón-Torres, F., Rivero-Calle, I., Vermont, C.L., Hagedoorn, N.N., Pokorn, M., Pollard, A.J., Schlapbach, L.J., Tsolia, M., Elefhteriou, I., Yeung, S., Zavadska, D., Fink, C., Voice, M., Zenz, W., Kohlmaier, B., Agyeman, P.K.A., Usuf, E., Secka, F., Groot, R. de, Levin, M., Flier, M. van der, and Emonts, M.

Abstract

01 februari 2023, Item does not contain fulltext, To assess and describe the aetiology and management of febrile illness in children with primary or acquired immunodeficiency at high risk of serious bacterial infection, as seen in emergency departments in tertiary hospitals. Prospective data on demographics, presenting features, investigations, microbiology, management, and outcome of patients within the 'Biomarker Validation in HR patients' database in PERFORM, were analysed. Immunocompromised children (< 18 years old) presented to fifteen European hospitals in nine countries, and one Gambian hospital, with fever or suspected infection and clinical indication for blood investigations. Febrile episodes were assigned clinical phenotypes using the validated PERFORM algorithm. Logistic regression was used to assess the effect size of predictive features of proven/presumed bacterial or viral infection. A total of 599 episodes in 482 children were analysed. Seventy-eight episodes (13.0%) were definite bacterial, 67 episodes probable bacterial (11.2%), and 29 bacterial syndrome (4.8%). Fifty-five were definite viral (9.2%), 49 probable viral (8.2%), and 23 viral syndrome (3.8%). One hundred ninety were unknown bacterial or viral infections (31.7%), and 108 had inflammatory or other non-infectious causes of fever (18.1%). Predictive features of proven/presumed bacterial infection were ill appearance (OR 3.1 (95% CI 2.1-4.6)) and HIV (OR 10.4 (95% CI 2.0-54.4)). Ill appearance reduced the odds of having a proven/presumed viral infection (OR 0.5 (95% CI 0.3-0.9)). A total of 82.1% had new empirical antibiotics started on admission (N = 492); 94.3% proven/presumed bacterial (N = 164), 66.1% proven/presumed viral (N = 84), and 93.2% unknown bacterial or viral infections (N = 177). Mortality was 1.9% (N = 11) and 87.1% made full recovery (N = 522). Conclusion: The aetiology of febrile illness in immunocompromised children is diverse. In one-third of cases, no cause for the fever will be identified. Justification for standard

Published
2023

8. Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study.

Author

Shah, P., Voice, M., Calvo-Bado, L., Rivero-Calle, I., Morris, S., Nijman, R., Broderick, C., De, T., Eleftheriou, I., Galassini, R., Khanijau, A., Kolberg, L., Kolnik, M., Rudzate, A., Sagmeister, M.G., Schweintzger, N.A., Secka, F., Thakker, C., Velden, F. van der, Vermont, C., Vincek, K., Agyeman, P.K.A., Cunnington, A.J., Groot, R. de, Emonts, M., Fidler, K., Kuijpers, T.W., Mommert-Tripon, M., Brengel-Pesce, K., Mallet, F., Moll, H., Paulus, S., Pokorn, M., Pollard, A., Schlapbach, L.J., Shen, C.F., Tsolia, M., Usuf, E., Flier, M. van der, Both, U. von, Yeung, S., Zavadska, D., Zenz, W., Wright, V., Carrol, E.D., Kaforou, M., Martinon-Torres, F., Fink, C., Levin, M., Herberg, J., Shah, P., Voice, M., Calvo-Bado, L., Rivero-Calle, I., Morris, S., Nijman, R., Broderick, C., De, T., Eleftheriou, I., Galassini, R., Khanijau, A., Kolberg, L., Kolnik, M., Rudzate, A., Sagmeister, M.G., Schweintzger, N.A., Secka, F., Thakker, C., Velden, F. van der, Vermont, C., Vincek, K., Agyeman, P.K.A., Cunnington, A.J., Groot, R. de, Emonts, M., Fidler, K., Kuijpers, T.W., Mommert-Tripon, M., Brengel-Pesce, K., Mallet, F., Moll, H., Paulus, S., Pokorn, M., Pollard, A., Schlapbach, L.J., Shen, C.F., Tsolia, M., Usuf, E., Flier, M. van der, Both, U. von, Yeung, S., Zavadska, D., Zenz, W., Wright, V., Carrol, E.D., Kaforou, M., Martinon-Torres, F., Fink, C., Levin, M., and Herberg, J.

Abstract

01 september 2023, Contains fulltext : 295917.pdf (Publisher’s version ) (Open Access), BACKGROUND: The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice. METHODS: Febrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed. FINDINGS: Of 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92-5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and E. coli (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively. INTERPRETATION: Most febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which feb

Published
2023

9. Clinical Symptoms, Laboratory Parameters and Long-Term Follow-up in a National DADA2 Cohort.

Author

Andriessen, M.V.E., Legger, G.E., Bredius, R.G.M., Gijn, M.E. van, Hak, A.E., Muller, P.C.E.H., Kamphuis, S., Klouwer, F.C.C., Kuijpers, T.W., Leavis, H.L., Nierkens, S., Rutgers, A., Veken, L.T. van der, Well, G.T.J. van, Mulders-Manders, C.M., Montfrans, J.M. van, Andriessen, M.V.E., Legger, G.E., Bredius, R.G.M., Gijn, M.E. van, Hak, A.E., Muller, P.C.E.H., Kamphuis, S., Klouwer, F.C.C., Kuijpers, T.W., Leavis, H.L., Nierkens, S., Rutgers, A., Veken, L.T. van der, Well, G.T.J. van, Mulders-Manders, C.M., and Montfrans, J.M. van

Abstract

Contains fulltext : 296537.pdf (Publisher’s version ) (Open Access), Deficiency of adenosine deaminase-2 (DADA2) is an autosomal recessive autoinflammatory disease with an extremely variable disease presentation. This paper provides a comprehensive overview of the Dutch DADA2 cohort. We performed a retrospective cohort study in 29 ADA2-deficient patients from 23 families with a median age at inclusion of 26 years. All patients had biallelic pathogenic variants in the ADA2 gene. The most common clinical findings included cutaneous involvement (79.3%), (hepato)splenomegaly (70.8%) and recurrent infections (58.6%). Stroke was observed in 41.4% of the patients. The main laboratory abnormalities were hypogammaglobulinemia and various cytopenias. Patients presented most often with a mixed phenotype involving vasculopathy, immunodeficiency and hematologic manifestations (62.1%). In this cohort, malignancies were reported in eight patients (27.6%), of whom five presented with a hematologic malignancy and two with a basal cell carcinoma. Four patients developed hemophagocytic lymphohistiocytosis (HLH) or an HLH-like episode, of whom three passed away during or shortly after the occurrence of HLH. TNF-inhibitors (TNFi) were effective in treating vasculopathy-associated symptoms and preventing stroke, but were hardly effective in the treatment of hematologic manifestations. Three patients underwent hematopoietic cell transplantation and two of them are doing well with complete resolution of DADA2-related symptoms. The overall mortality in this cohort was 17.2%. In conclusion, this cohort describes the clinical, genetic and laboratory findings of 29 Dutch DADA2 patients. We describe the occurrence of HLH as a life-threatening disease complication and report a relatively high incidence of malignancies and mortality.

Published
2023

10. Transient anti-cytokine autoantibodies superimpose the hyperinflammatory response in Kawasaki disease and multisystem inflammatory syndrome in children: a comparative cohort study on correlates of disease

Author

Netea, Stejara A., Biesbroek, Giske, Stijn, Diana van, Ijspeert, Hanna, Made, C.I. van der, Jansen, Machiel H., Veerdonk, F.L. van de, Dik, Willem A., Kuijpers, T.W., Netea, Stejara A., Biesbroek, Giske, Stijn, Diana van, Ijspeert, Hanna, Made, C.I. van der, Jansen, Machiel H., Veerdonk, F.L. van de, Dik, Willem A., and Kuijpers, T.W.

Abstract

Item does not contain fulltext

Published
2023

13. Longitudinal SARS-CoV-2 humoral response in MS patients with and without SARS-CoV-2 infection prior to vaccination

Author

van Dam, K.P.J., Hogenboom, L., Stalman, E.W., Kummer, L.Y.L., Steenhuis, M., Keijser, J.B.D., ten Brinke, A., van Ham, S.M., Kuijpers, T.W., Rispens, T., Wieske, L., Eftimov, F., Strijbis, E.M., Killestein, J., van Kempen, Z.L.E., Graduate School, Neurology, Landsteiner Laboratory, AII - Inflammatory diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, AII - Infectious diseases, ARD - Amsterdam Reproduction and Development, ANS - Neuroinfection & -inflammation, Paediatrics, EURO-NMD, Pediatrics, Amsterdam Neuroscience - Neuroinfection & -inflammation, and SILS Other Research (FNWI)

Subjects
Neurology, SARS-CoV-2, COVID-19, disease modifying treatment, Neurology (clinical), multiple sclerosis, humoral response
Abstract

IntroductionDuring the COVID-19 pandemic, certain disease modifying therapies (DMTs) used in multiple sclerosis (MS), such as anti-CD20 therapies, have been associated with decreased humoral responses after SARS-CoV-2 vaccination. Hybrid immunity, referring to immunity after both vaccination and SARS-CoV-2 infection might increase humoral responses.MethodsThis was a substudy of two prospective cohort studies on SARS-CoV-2 antibodies after SARS-CoV-2 infection and vaccination. RBD-specific IgG titers of patients with MS and healthy controls who had experienced SARS-CoV-2 infection prior to the first vaccination were compared with those patients and healthy controls without prior infection. Humoral responses were measured at various time points after SARS-CoV-2 infection in convalescent patients and all patients prior to the first vaccination, 28 days after the first vaccination, and 28 days after the second vaccination.ResultsOne hundred and two individuals [of which 34 patients with MS and DMTs (natalizumab or ocrelizumab), 30 patients without DMTs, and 38 healthy controls] were included. Fifty one of these individuals were convalescent. Median SARS-CoV-2 antibody titers were higher after the first vaccination in convalescent individuals compared with individuals without infection prior to vaccination. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody titers were comparable after the second vaccination in patients with MS with and without prior infection. However, in the convalescent ocrelizumab-treated patients, SARS-CoV-2 antibody titers did not increase after vaccinations.ConclusionIn patients with MS without anti-CD20 therapies, SARS-CoV-2 infection before vaccination increases humoral responses after the first vaccination, similar to the healthy controls. In patients with MS treated with ocrelizumab (convalescent and non-convalescent), humoral responses remained low.

Published
2022
Full Text
View/download PDF

14. Inflammatory responses in SARS-CoV-2 associated Multisystem Inflammatory Syndrome and Kawasaki Disease in children: An observational study

Author

Biesbroek, G., Kapitein, B., Kuipers, I.M., Gruppen, M.P., Stijn, D. van, Peros, T.E., Veenendaal, M. van, Jansen, M.H.A., Zee, C.W. van der, Kuip, M. van der, Asmuth, E.G.J. von, Mooij, M.G., Boer, M.E.J. den, Landman, G.W., Houten, M.A. van, Schonenberg-Meinema, D., Furth, A.M.T. van, Hensbroek, M.B. van, Scherpbier, H., Meijgaarden, K.E. van, Ottenhoff, T.H.M., Joosten, S.A., Ketharanathan, N., Blink, M., Brackel, C.L.H., Zaaijer, H.L., Hombrink, P., Berg, J.M. van den, Buddingh, E.P., Kuijpers, T.W., Pediatrics, Amsterdam Reproduction & Development (AR&D), AII - Inflammatory diseases, Radiation Oncology, Paediatrics, Paediatric Cardiology, APH - Methodology, APH - Quality of Care, Paediatric Infectious Diseases / Rheumatology / Immunology, General Paediatrics, 04 Woman - Child, Paediatric Intensive Care, Graduate School, Global Health, APH - Global Health, Landsteiner Laboratory, Medical Microbiology and Infection Prevention, ARD - Amsterdam Reproduction and Development, and Pediatric Surgery

Subjects
Inflammation, Multidisciplinary, Interleukin-6, SARS-CoV-2, Humans, COVID-19, Cytokines, Mucocutaneous Lymph Node Syndrome, Child, Antibodies, Viral, Connective Tissue Diseases
Abstract

Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe inflammatory disease in children related to SARS-CoV-2 with multisystem involvement including marked cardiac dysfunction and clinical symptoms that can resemble Kawasaki Disease (KD). We hypothesized that MIS-C and KD might have commonalities as well as unique inflammatory responses and studied these responses in both diseases. In total, fourteen children with MIS-C (n=8) and KD (n=6) were included in the period of March-June 2020. Clinical and routine blood parameters, cardiac follow-up, SARS-CoV-2-specific antibodies and CD4+ T-cell responses, and cytokine-profiles were determined in both groups. In contrast to KD patients, all MIS-C patients had positive Spike protein-specific CD3+CD4+ T-cell responses. MIS-C and KD patients displayed marked hyper-inflammation with high expression of serum cytokines, including the drug-targetable interleukin (IL)-6 and IFN-γ associated chemokines CXCL9, 10 and 11, which decreased at follow-up. No statistical differences were observed between groups. Clinical outcomes were all favourable without cardiac sequelae at 6 months follow-up. In conclusion, MIS-C and KD-patients both displayed cytokine-associated hyper-inflammation with several high levels of drug-targetable cytokines.

Published
2022
Full Text
View/download PDF

15. 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
Full Text
View/download PDF

17. S100A8/A9 Is a Marker for the Release of Neutrophil Extracellular Traps and Induces Neutrophil Activation

Author

Sprenkeler, E.G.G., Zandstra, J., Kleef, N.D. van, Goetschalckx, I., Verstegen, B., Aarts, C.E.M., Janssen, H., Tool, A.T., Mierlo, G van, Bruggen, R. van, Jongerius, I., Kuijpers, T.W., Sprenkeler, E.G.G., Zandstra, J., Kleef, N.D. van, Goetschalckx, I., Verstegen, B., Aarts, C.E.M., Janssen, H., Tool, A.T., Mierlo, G van, Bruggen, R. van, Jongerius, I., and Kuijpers, T.W.

Abstract

Item does not contain fulltext

Published
2022

18. Heterozygous NOTCH1 Variants Cause CNS Immune Activation and Microangiopathy

Author

Helman, G., Zarekiani, P., Tromp, S.A.M., Andrews, A., Botto, L.D., Bonkowsky, J.L., Chassevent, A., Giorgio, E., Pippucci, T., Wei, S., Smith-Hicks, C., Vaula, G., Willemsen, M.A.A.P., Schimmel, M., Vollert, K., Shimizu, F., Kanda, T., Lynch, M., Roscioli, T., Taft, R.J., Simons, C., Bugiani, M., Kuijpers, T.W., Knaap, M.S. van der, Helman, G., Zarekiani, P., Tromp, S.A.M., Andrews, A., Botto, L.D., Bonkowsky, J.L., Chassevent, A., Giorgio, E., Pippucci, T., Wei, S., Smith-Hicks, C., Vaula, G., Willemsen, M.A.A.P., Schimmel, M., Vollert, K., Shimizu, F., Kanda, T., Lynch, M., Roscioli, T., Taft, R.J., Simons, C., Bugiani, M., Kuijpers, T.W., and Knaap, M.S. van der

Abstract

Item does not contain fulltext, NOTCH1 belongs to the NOTCH family of proteins that regulate cell fate and inflammatory responses. Somatic and germline NOTCH1 variants have been implicated in cancer, Adams-Oliver syndrome, and cardiovascular defects. We describe 7 unrelated patients grouped by the presence of leukoencephalopathy with calcifications and heterozygous de novo gain-of-function variants in NOTCH1. Immunologic profiling showed upregulated CSF IP-10, a cytokine secreted downstream of NOTCH1 signaling. Autopsy revealed extensive leukoencephalopathy and microangiopathy with vascular calcifications. This evidence implicates that heterozygous gain-of-function variants in NOTCH1 lead to a chronic central nervous system (CNS) inflammatory response resulting in a calcifying microangiopathy with leukoencephalopathy. ANN NEUROL 2022;92:895-901.

Published
2022

19. Megalobastic anemia, infantile leukemia, and immunodeficiency caused by a novel homozygous mutation in the DHFR gene

Author

Kuijpers, T.W., Vries, A.C.M. de, Leeuwen, E.M. van, Ermens, A., Pont, S., Smith, D.E., Wamelink, M.M., Mensenkamp, A.R., Nelen, M.R., Allen, H., Pals, S.T., Beverloo, B.H.B., Huidekoper, H.H., Wagner, A., Kuijpers, T.W., Vries, A.C.M. de, Leeuwen, E.M. van, Ermens, A., Pont, S., Smith, D.E., Wamelink, M.M., Mensenkamp, A.R., Nelen, M.R., Allen, H., Pals, S.T., Beverloo, B.H.B., Huidekoper, H.H., and Wagner, A.

Abstract

Item does not contain fulltext

Published
2022

20. Breakthrough SARS-CoV-2 infections with the delta (B.1.617.2) variant in vaccinated patients with immune-mediated inflammatory diseases using immunosuppressants: a substudy of two prospective cohort studies

Author

Boekel, L., Stalman, E.W., Wieske, L., Hooijberg, F., Dam, K.P.J. van, Besten, Y.R., Kummer, L.Y., Steenhuis, M., Kempen, Z.L.E. van, Killestein, J., Volkers, A.G., Tas, S.W., Kooi, A.J. van der, Raaphorst, J., Löwenberg, M., Takkenberg, R.B., d'Haens, G., 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., Els, C. van, Wit, J. de, Rutgers, A., Leeuw, K. de, Horváth, B., Verschuuren, J., Ruiter, A.M. de, Ouwerkerk, L., 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.J., Schreurs, C.R.G., Pol, W.Ludo van der, Goedee, H.S., Vogelzang, E.H., Leeuw, M. de, Atiqi, S., Vollenhoven, R. van, Gerritsen, M, Horst-Bruinsma, I.E. van der, Lems, W.F., Nurmohamed, M.T., Boers, Maarten, Keijzer, Sofie, Keijser, J. de, Sandt, C., Boogaard, A., Cristianawati, O., Brinke, A. Ten, Verstegen, N.J., Zwinderman, K.A.H., Ham, S.M. van, Rispens, T., Kuijpers, T.W., Wolbink, G., Eftimov, F., Boekel, L., Stalman, E.W., Wieske, L., Hooijberg, F., Dam, K.P.J. van, Besten, Y.R., Kummer, L.Y., Steenhuis, M., Kempen, Z.L.E. van, Killestein, J., Volkers, A.G., Tas, S.W., Kooi, A.J. van der, Raaphorst, J., Löwenberg, M., Takkenberg, R.B., d'Haens, G., 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., Els, C. van, Wit, J. de, Rutgers, A., Leeuw, K. de, Horváth, B., Verschuuren, J., Ruiter, A.M. de, Ouwerkerk, L., 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.J., Schreurs, C.R.G., Pol, W.Ludo van der, Goedee, H.S., Vogelzang, E.H., Leeuw, M. de, Atiqi, S., Vollenhoven, R. van, Gerritsen, M, Horst-Bruinsma, I.E. van der, Lems, W.F., Nurmohamed, M.T., Boers, Maarten, Keijzer, Sofie, Keijser, J. de, Sandt, C., Boogaard, A., Cristianawati, O., Brinke, A. Ten, Verstegen, N.J., Zwinderman, K.A.H., Ham, S.M. van, Rispens, T., Kuijpers, T.W., Wolbink, G., and Eftimov, F.

Abstract

Item does not contain fulltext, BACKGROUND: Concerns have been raised regarding the risks of SARS-CoV-2 breakthrough infections in vaccinated patients with immune-mediated inflammatory diseases treated with immunosuppressants, but clinical data on breakthrough infections are still scarce. The primary objective of this study was to compare the incidence and severity of SARS-CoV-2 breakthrough infections between patients with immune-mediated inflammatory diseases using immunosuppressants, and controls (patients with immune-mediated inflammatory diseases not taking immunosuppressants and healthy controls) who had received full COVID-19 vaccinations. The secondary objective was to explore determinants of breakthrough infections of the delta (B.1.617.2) variant of SARS-CoV-2, including humoral immune responses after vaccination. METHODS: In this substudy, we pooled data collected in two large ongoing prospective multicentre cohort studies conducted in the Netherlands (Target to-B! [T2B!] study and Amsterdam Rheumatology Center COVID [ARC-COVID] study). Both studies recruited adult patients (age ≥18 years) with immune-mediated inflammatory diseases and healthy controls. We sourced clinical data from standardised electronic case record forms, digital questionnaires, and medical files. We only included individuals who were vaccinated against SARS-CoV-2. For T2B!, participants were recruited between Feb 2 and Aug 1, 2021, and for ARC-COVID, participants were recruited between April 26, 2020, and March 1, 2021. In this study we assessed data on breakthrough infections collected between July 1 and Dec 15, 2021, a period in which the delta SARS-CoV-2 variant was the dominant variant in the Netherlands. We defined a SARS-CoV-2 breakthrough infection as a PCR-confirmed or antigen test-confirmed SARS-CoV-2 infection that occurred at least 14 days after vaccination. All breakthrough infections during this period were assumed to be due to the delta variant due to its dominance during the study period. We analysed

Published
2022

21. Variation in CFHR3 determines susceptibility to meningococcal disease by controlling factor H concentrations

Author

Kumar, Vikrant, Pouw, R.B., Autio, M.I., Sagmeister, M.G., Phua, Z. Yang, Borghini, L., Wright, V.J., Hoggart, C., Pan, B., Tan, A., Binder, A., Brouwer, M.C.T., Pinnock, E., Groot, R. de, Hazelzet, J., Emonts, M., Flier, M. van der, Reiter, K., Nöthen, M.M., Hoffmann, P., consortium, E., Schlapbach, L.J., Bellos, E., Anderson, S., Secka, F., Martinón-Torres, F., Salas, A., Fink, C., Carrol, E.D., Pollard, A.J., Coin, L.J., Zenz, W., Wouters, D., Ang, L. Teng, Hibberd, M.L., Levin, M., Kuijpers, T.W., Davila, S., Kumar, Vikrant, Pouw, R.B., Autio, M.I., Sagmeister, M.G., Phua, Z. Yang, Borghini, L., Wright, V.J., Hoggart, C., Pan, B., Tan, A., Binder, A., Brouwer, M.C.T., Pinnock, E., Groot, R. de, Hazelzet, J., Emonts, M., Flier, M. van der, Reiter, K., Nöthen, M.M., Hoffmann, P., consortium, E., Schlapbach, L.J., Bellos, E., Anderson, S., Secka, F., Martinón-Torres, F., Salas, A., Fink, C., Carrol, E.D., Pollard, A.J., Coin, L.J., Zenz, W., Wouters, D., Ang, L. Teng, Hibberd, M.L., Levin, M., Kuijpers, T.W., and Davila, S.

Abstract

Contains fulltext : 282924.pdf (Publisher’s version ) (Open Access)

Published
2022

22. Antibody development and disease severity of COVID-19 in non-immunised patients with rheumatic immune-mediated inflammatory diseases: data from a prospective cohort study

Author

Boekel, L., Hooijberg, F., Vogelzang, E.H., Besten, Y.R., Leeuw, M. de, Atiqi, S., Vollenhoven, R.F. van, Wijbrandts, C.A., Gerritsen, M, Krieckaert, C., Dijkshoorn, B., Bakhlakh, S., Crooijmans, J.J., Voskuyl, A., Horst-Bruinsma, I.E. van der, Lems, W., Kuijpers, T.W., Ham, S.M. van, Wieske, L., Eftimov, F., Kummer, L.Y., Dam, P.K. van, Stalman, E.W., Steenhuis, M., Keijzer, Sofie, Cristianawati, O., Keijser, J. de, Loeff, F.C., Tas, S.W., Nurmohamed, M.T., Boers, Maarten, Rispens, T., Wolbink, G., Boekel, L., Hooijberg, F., Vogelzang, E.H., Besten, Y.R., Leeuw, M. de, Atiqi, S., Vollenhoven, R.F. van, Wijbrandts, C.A., Gerritsen, M, Krieckaert, C., Dijkshoorn, B., Bakhlakh, S., Crooijmans, J.J., Voskuyl, A., Horst-Bruinsma, I.E. van der, Lems, W., Kuijpers, T.W., Ham, S.M. van, Wieske, L., Eftimov, F., Kummer, L.Y., Dam, P.K. van, Stalman, E.W., Steenhuis, M., Keijzer, Sofie, Cristianawati, O., Keijser, J. de, Loeff, F.C., Tas, S.W., Nurmohamed, M.T., Boers, Maarten, Rispens, T., and Wolbink, G.

Abstract

Contains fulltext : 251778.pdf (Publisher’s version ) (Open Access), BACKGROUND: Research on the disease severity of COVID-19 in patients with rheumatic immune-mediated inflammatory diseases (IMIDs) has been inconclusive, and long-term prospective data on the development of SARS-CoV-2 antibodies in these patients are lacking. METHODS: Adult patients with rheumatic IMIDs from the Amsterdam Rheumatology and Immunology Center, Amsterdam were invited to participate. All patients were asked to recruit their own sex-matched and age-matched control subject. Clinical data were collected via online questionnaires (at baseline, and after 1-4 and 5-9 months of follow-up). Serum samples were collected twice and analysed for the presence of SARS-CoV-2-specific antibodies. Subsequently, IgG titres were quantified in samples with a positive test result. FINDINGS: In total, 3080 consecutive patients and 1102 controls with comparable age and sex distribution were included for analyses. Patients were more frequently hospitalised compared with controls when infected with SARS-CoV-2; 7% vs 0.7% (adjusted OR: 7.33, 95% CI: 0.96 to 55.77). Only treatment with B-cell targeting therapy was independently associated with an increased risk of COVID-19-related hospitalisation (adjusted OR: 14.62, 95% CI: 2.31 to 92.39). IgG antibody titres were higher in hospitalised compared with non-hospitalised patients, and slowly declined with time in similar patterns for patients in all treatment subgroups and controls. INTERPRETATION: We observed that patients with rheumatic IMIDs, especially those treated with B-cell targeting therapy, were more likely to be hospitalised when infected with SARS-CoV-2. Treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and biological DMARDs other than B-cell targeting agents is unlikely to have negative effects on the development of long-lasting humoral immunity against SARS-CoV-2.

Published
2022

24. Longitudinal humoral response after SARS-CoV-2 vaccination in ocrelizumab treated MS patients: To wait and repopulate?

Author

van Kempen, Z.L.E., primary, Wieske, L., additional, Stalman, E.W., additional, Kummer, L. Y. L, additional, van Dam, P.J., additional, Volkers, A.G., additional, Boekel, L., additional, Toorop, A.A., additional, Strijbis, E.M.M., additional, Tas, S.W., additional, Wolbink, G.J., additional, Löwenberg, M., additional, van Sandt, C., additional, ten Brinke, A., additional, Verstegen, N.J.M., additional, Steenhuis, M., additional, Kuijpers, T.W., additional, van Ham, S.M., additional, Rispens, T., additional, Eftimov, F., additional, and Killestein, J., additional

Published
2022
Full Text
View/download PDF

25. Implementation of Early Next-Generation Sequencing for Inborn Errors of Immunity: A Prospective Observational Cohort Study of Diagnostic Yield and Clinical Implications in Dutch Genome Diagnostic Centers

Author

Elsink, K., Huibers, M.M.H., Hollink, I.H., Simons, A., Zonneveld-Huijssoon, E., Veken, L.T. van der, Leavis, H.L., Henriet, S.S.V., Deuren, M. van, Veerdonk, F.L. van de, Potjewijd, J., Berghuis, D., Dalm, V.A., Vermont, C.L., Ven, A.A.J.M. van de, Lambeck, A.J.A., Abbott, K.M., Hagen, P.M. van, Bree, G.J. de, Kuijpers, T.W., Frederix, G.W., Gijn, M.E. van, Montfrans, J.M., Consortium, G.F.f.P.I.D., Elsink, K., Huibers, M.M.H., Hollink, I.H., Simons, A., Zonneveld-Huijssoon, E., Veken, L.T. van der, Leavis, H.L., Henriet, S.S.V., Deuren, M. van, Veerdonk, F.L. van de, Potjewijd, J., Berghuis, D., Dalm, V.A., Vermont, C.L., Ven, A.A.J.M. van de, Lambeck, A.J.A., Abbott, K.M., Hagen, P.M. van, Bree, G.J. de, Kuijpers, T.W., Frederix, G.W., Gijn, M.E. van, Montfrans, J.M., and Consortium, G.F.f.P.I.D.

Abstract

Contains fulltext : 244016.pdf (Publisher’s version ) (Open Access)

Published
2021

26. National external quality assessment for next-generation sequencing-based diagnostics of primary immunodeficiencies

Author

Elsink, K., Huibers, M.M.H., Hollink, I., Veken, L.T. van der, Ernst, R.F., Simons, A., Zonneveld-Huijssoon, E., Hout, A.H. van der, Abbott, K.M., Hoischen, A., Pieterse, M., Kuijpers, T.W., Montfrans, J.M., Gijn, M.E. van, Elsink, K., Huibers, M.M.H., Hollink, I., Veken, L.T. van der, Ernst, R.F., Simons, A., Zonneveld-Huijssoon, E., Hout, A.H. van der, Abbott, K.M., Hoischen, A., Pieterse, M., Kuijpers, T.W., Montfrans, J.M., and Gijn, M.E. van

Abstract

Contains fulltext : 231689.pdf (Publisher’s version ) (Closed access), Dutch genome diagnostic centers (GDC) use next-generation sequencing (NGS)-based diagnostic applications for the diagnosis of primary immunodeficiencies (PIDs). The interpretation of genetic variants in many PIDs is complicated because of the phenotypic and genetic heterogeneity. To analyze uniformity of variant filtering, interpretation, and reporting in NGS-based diagnostics for PID, an external quality assessment was performed. Four main Dutch GDCs participated in the quality assessment. Unannotated variant call format (VCF) files of two PID patient analyses per laboratory were distributed among the four GDCs, analyzed, and interpreted (eight analyses in total). Variants that would be reported to the clinician and/or advised for further investigation were compared between the centers. A survey measuring the experiences of clinical laboratory geneticists was part of the study. Analysis of samples with confirmed diagnoses showed that all centers reported at least the variants classified as likely pathogenic (LP) or pathogenic (P) variants in all samples, except for variants in two genes (PSTPIP1 and BTK). The absence of clinical information complicated correct classification of variants. In this external quality assessment, the final interpretation and conclusions of the genetic analyses were uniform among the four participating genetic centers. Clinical and immunological data provided by a medical specialist are required to be able to draw proper conclusions from genetic data.

Published
2021

27. Genetic biomarkers for intravenous immunoglobulin response in chronic inflammatory demyelinating polyradiculoneuropathy

Author

Kuitwaard, K. (Krista), Doorn, P.A. (Pieter) van, Bengrine, T. (Thiziri), Rijs, W. (Wouter) van, Baas, F. (Frank), Nagelkerke, S.Q. (Sietse Q.), Kuijpers, T.W. (Taco W.), Fokkink, W.-J.R. (Willem-Jan), Bunschoten, C. (Carina), Broers, M.C. (Merel C.), Willemsen, S.P. (Sten P.), Jacobs, B.C. (Bart), Huizinga, R. (Ruth), Kuitwaard, K. (Krista), Doorn, P.A. (Pieter) van, Bengrine, T. (Thiziri), Rijs, W. (Wouter) van, Baas, F. (Frank), Nagelkerke, S.Q. (Sietse Q.), Kuijpers, T.W. (Taco W.), Fokkink, W.-J.R. (Willem-Jan), Bunschoten, C. (Carina), Broers, M.C. (Merel C.), Willemsen, S.P. (Sten P.), Jacobs, B.C. (Bart), and Huizinga, R. (Ruth)

Abstract

Background and purpose: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a clinical and electrophysiological heterogeneous immune-mediated polyneuropathy. Int

Published
2021
Full Text
View/download PDF

28. Immunoglobulin Replacement Therapy Versus Antibiotic Prophylaxis as Treatment for Incomplete Primary Antibody Deficiency

Author

Smits, B.M., Budde, I. Kleine, Vries, E de, Berge, I.J. Ten, Bredius, R.G., Deuren, M. van, Dissel, J.T. van, Ellerbroek, P.M., Flier, M. van der, Hagen, P.M. van, Nieuwhof, C., Rutgers, B., Sanders, L., Simon, A., Kuijpers, T.W., Montfrans, J.M., Smits, B.M., Budde, I. Kleine, Vries, E de, Berge, I.J. Ten, Bredius, R.G., Deuren, M. van, Dissel, J.T. van, Ellerbroek, P.M., Flier, M. van der, Hagen, P.M. van, Nieuwhof, C., Rutgers, B., Sanders, L., Simon, A., Kuijpers, T.W., and Montfrans, J.M.

Abstract

Contains fulltext : 232451.pdf (Publisher’s version ) (Open Access), BACKGROUND: Patients with an IgG subclass deficiency (IgSD) ± specific polysaccharide antibody deficiency (SPAD) often present with recurrent infections. Previous retrospective studies have shown that prophylactic antibiotics (PA) and immunoglobulin replacement therapy (IRT) can both be effective in preventing these infections; however, this has not been confirmed in a prospective study. OBJECTIVE: To compare the efficacy of PA and IRT in a randomized crossover trial. METHODS: A total of 64 patients (55 adults and 9 children) were randomized (2:2) between two treatment arms. Treatment arm A began with 12 months of PA, and treatment arm B began with 12 months of IRT. After a 3-month bridging period with cotrimoxazole, the treatment was switched to 12 months of IRT and PA, respectively. The efficacy (measured by the incidence of infections) and proportion of related adverse events in the two arms were compared. RESULTS: The overall efficacy of the two regimens did not differ (p = 0.58, two-sided Wilcoxon signed-rank test). A smaller proportion of patients suffered a related adverse event while using PA (26.8% vs. 60.3%, p < 0.0003, chi-squared test). Patients with persistent infections while using PA suffered fewer infections per year after switching to IRT (2.63 vs. 0.64, p < 0.01). CONCLUSION: We found comparable efficacy of IRT and PA in patients with IgSD ± SPAD. Patients with persistent infections during treatment with PA had less infections after switching to IRT. CLINICAL IMPLICATION: Given the costs and associated side-effects of IRT, it should be reserved for patients with persistent infections despite treatment with PA.

Published
2021

29. Biomarkers for the Discrimination of Acute Kawasaki Disease From Infections in Childhood

Author

Zandstra, J. van de Geer, A. Tanck, M.W.T. van Stijn-Bringas Dimitriades, D. Aarts, C.E.M. Dietz, S.M. van Bruggen, R. Schweintzger, N.A. Zenz, W. Emonts, M. Zavadska, D. Pokorn, M. Usuf, E. Moll, H.A. Schlapbach, L.J. Carrol, E.D. Paulus, S. Tsolia, M. Fink, C. Yeung, S. Shimizu, C. Tremoulet, A. Galassini, R. Wright, V.J. Martinón-Torres, F. Herberg, J. Burns, J. Levin, M. Kuijpers, T.W. EUCLIDS Consortium, PERFORM Consortium UK Kawasaki Disease Genetics Study Network

Abstract

Background: Kawasaki disease (KD) is a vasculitis of early childhood mimicking several infectious diseases. Differentiation between KD and infectious diseases is essential as KD's most important complication—the development of coronary artery aneurysms (CAA)—can be largely avoided by timely treatment with intravenous immunoglobulins (IVIG). Currently, KD diagnosis is only based on clinical criteria. The aim of this study was to evaluate whether routine C-reactive protein (CRP) and additional inflammatory parameters myeloid-related protein 8/14 (MRP8/14 or S100A8/9) and human neutrophil-derived elastase (HNE) could distinguish KD from infectious diseases. Methods and Results: The cross-sectional study included KD patients and children with proven infections as well as febrile controls. Patients were recruited between July 2006 and December 2018 in Europe and USA. MRP8/14, CRP, and HNE were assessed for their discriminatory ability by multiple logistic regression analysis with backward selection and receiver operator characteristic (ROC) curves. In the discovery cohort, the combination of MRP8/14+CRP discriminated KD patients (n = 48) from patients with infection (n = 105), with area under the ROC curve (AUC) of 0.88. The HNE values did not improve discrimination. The first validation cohort confirmed the predictive value of MRP8/14+CRP to discriminate acute KD patients (n = 26) from those with infections (n = 150), with an AUC of 0.78. The second validation cohort of acute KD patients (n = 25) and febrile controls (n = 50) showed an AUC of 0.72, which improved to 0.84 when HNE was included. Conclusion: When used in combination, the plasma markers MRP8/14, CRP, and HNE may assist in the discrimination of KD from both proven and suspected infection. © Copyright © 2020 Zandstra, van de Geer, Tanck, van Stijn-Bringas Dimitriades, Aarts, Dietz, van Bruggen, Schweintzger, Zenz, Emonts, Zavadska, Pokorn, Usuf, Moll, Schlapbach, Carrol, Paulus, Tsolia, Fink, Yeung, Shimizu, Tremoulet, Galassini, Wright, Martinón-Torres, Herberg, Burns, Levin, Kuijpers, EUCLIDS Consortium, PERFORM Consortium and UK Kawasaki Disease Genetics Study Network.

Published
2020

30. Characterization of the clinical and immunologic phenotype and management of 157 individuals with 56 distinct heterozygous NFKB1 mutations

Author

Lorenzini, T., Fliegauf, M., Klammer, N., Frede, N., Proietti, M., Bulashevska, A., Camacho-Ordonez, N., Varjosalo, M., Kinnunen, M., Vries, E de, Meer, J.W.M. van der, Ameratunga, R., Roifman, C.M., Schejter, Y.D., Kobbe, R., Hautala, T., Atschekzei, F., Schmidt, R.E., Schröder, C., Stepensky, P., Shadur, B., Pedroza, L.A., Flier, M. van der, Martínez-Gallo, M., Gonzalez-Granado, L.I., Allende, L.M., Shcherbina, A., Kuzmenko, N., Zakharova, V., Neves, J.F., Svec, P., Fischer, U., Ip, W., Bartsch, O., Barış, S., Klein, C., Geha, R., Chou, J., Alosaimi, M., Weintraub, L., Boztug, K., Hirschmugl, T., Vilela, M.M. Dos Santos, Holzinger, D., Seidl, M., Lougaris, V., Plebani, A., Alsina, L., Piquer-Gibert, M., Deyà-Martínez, A., Slade, C.A., Aghamohammadi, A., Abolhassani, H., Hammarström, L., Kuismin, O., Helminen, M., Allen, H.L., Thaventhiran, J.E., Freeman, A.F., Cook, M., Bakhtiar, S., Christiansen, M., Cunningham-Rundles, C., Patel, N.C., Rae, W., Niehues, T., Brauer, N., Syrjänen, J., Seppänen, M.R.J., Burns, S.O., Tuijnenburg, P., Kuijpers, T.W., Warnatz, K., Grimbacher, B., Lorenzini, T., Fliegauf, M., Klammer, N., Frede, N., Proietti, M., Bulashevska, A., Camacho-Ordonez, N., Varjosalo, M., Kinnunen, M., Vries, E de, Meer, J.W.M. van der, Ameratunga, R., Roifman, C.M., Schejter, Y.D., Kobbe, R., Hautala, T., Atschekzei, F., Schmidt, R.E., Schröder, C., Stepensky, P., Shadur, B., Pedroza, L.A., Flier, M. van der, Martínez-Gallo, M., Gonzalez-Granado, L.I., Allende, L.M., Shcherbina, A., Kuzmenko, N., Zakharova, V., Neves, J.F., Svec, P., Fischer, U., Ip, W., Bartsch, O., Barış, S., Klein, C., Geha, R., Chou, J., Alosaimi, M., Weintraub, L., Boztug, K., Hirschmugl, T., Vilela, M.M. Dos Santos, Holzinger, D., Seidl, M., Lougaris, V., Plebani, A., Alsina, L., Piquer-Gibert, M., Deyà-Martínez, A., Slade, C.A., Aghamohammadi, A., Abolhassani, H., Hammarström, L., Kuismin, O., Helminen, M., Allen, H.L., Thaventhiran, J.E., Freeman, A.F., Cook, M., Bakhtiar, S., Christiansen, M., Cunningham-Rundles, C., Patel, N.C., Rae, W., Niehues, T., Brauer, N., Syrjänen, J., Seppänen, M.R.J., Burns, S.O., Tuijnenburg, P., Kuijpers, T.W., Warnatz, K., and Grimbacher, B.

Abstract

Item does not contain fulltext, BACKGROUND: An increasing number of NFKB1 variants are being identified in patients with heterogeneous immunologic phenotypes. OBJECTIVE: To characterize the clinical and cellular phenotype as well as the management of patients with heterozygous NFKB1 mutations. METHODS: In a worldwide collaborative effort, we evaluated 231 individuals harboring 105 distinct heterozygous NFKB1 variants. To provide evidence for pathogenicity, each variant was assessed in silico; in addition, 32 variants were assessed by functional in vitro testing of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) signaling. RESULTS: We classified 56 of the 105 distinct NFKB1 variants in 157 individuals from 68 unrelated families as pathogenic. Incomplete clinical penetrance (70%) and age-dependent severity of NFKB1-related phenotypes were observed. The phenotype included hypogammaglobulinemia (88.9%), reduced switched memory B cells (60.3%), and respiratory (83%) and gastrointestinal (28.6%) infections, thus characterizing the disorder as primary immunodeficiency. However, the high frequency of autoimmunity (57.4%), lymphoproliferation (52.4%), noninfectious enteropathy (23.1%), opportunistic infections (15.7%), autoinflammation (29.6%), and malignancy (16.8%) identified NF-κB1-related disease as an inborn error of immunity with immune dysregulation, rather than a mere primary immunodeficiency. Current treatment includes immunoglobulin replacement and immunosuppressive agents. CONCLUSIONS: We present a comprehensive clinical overview of the NF-κB1-related phenotype, which includes immunodeficiency, autoimmunity, autoinflammation, and cancer. Because of its multisystem involvement, clinicians from each and every medical discipline need to be made aware of this autosomal-dominant disease. Hematopoietic stem cell transplantation and NF-κB1 pathway-targeted therapeutic strategies should be considered in the future.

Published
2020

31. Biomarkers for the Discrimination of Acute Kawasaki Disease From Infections in Childhood

Author

Zandstra, J. (Judith), van de Geer, A. (Annemarie), Tanck, M.W.T. (Michael), van Stijn-Bringas Dimitriades, D. (Diana), Aarts, C.E.M. (Cathelijn E. M.), Dietz, S.M. (Sanne M.), Bruggen, R. (Robin) van, Schweintzger, N.A. (Nina A.), Zenz, W. (Werner), Emonts, M. (Marieke), Zavadska, D. (Dace), Pokorn, M. (Marko), Usuf, E. (Effua), Moll, H.A. (Henriëtte), Schlapbach, L.J. (Luregn), Carrol, E.D. (Enitan), Paulus, S. (Stephane), Tsolia, M. (Maria), Fink, C. (Colin), Yeung, S. (Shunmay), Shimizu, C. (Chisato), Tremoulet, A. (Adriana), Galassini, R. (Rachel), Wright, V.J. (Victoria), Martinón-Torres, F. (Federico), Herberg, J. (Jethro), Burns, J. (Jane), Levin, M. (Michael), Kuijpers, T.W. (Taco W.), Zandstra, J. (Judith), van de Geer, A. (Annemarie), Tanck, M.W.T. (Michael), van Stijn-Bringas Dimitriades, D. (Diana), Aarts, C.E.M. (Cathelijn E. M.), Dietz, S.M. (Sanne M.), Bruggen, R. (Robin) van, Schweintzger, N.A. (Nina A.), Zenz, W. (Werner), Emonts, M. (Marieke), Zavadska, D. (Dace), Pokorn, M. (Marko), Usuf, E. (Effua), Moll, H.A. (Henriëtte), Schlapbach, L.J. (Luregn), Carrol, E.D. (Enitan), Paulus, S. (Stephane), Tsolia, M. (Maria), Fink, C. (Colin), Yeung, S. (Shunmay), Shimizu, C. (Chisato), Tremoulet, A. (Adriana), Galassini, R. (Rachel), Wright, V.J. (Victoria), Martinón-Torres, F. (Federico), Herberg, J. (Jethro), Burns, J. (Jane), Levin, M. (Michael), and Kuijpers, T.W. (Taco W.)

Abstract

Background: Kawasaki disease (KD) is a vasculitis of early childhood mimicking several infectious diseases. Differentiation between KD and infectious diseases is essential as KD's most important complication—the development of coronary artery aneurysms (CAA)—can be largely avoided by timely treatment with intravenous immunoglobulins (IVIG). Currently, KD diagnosis is only based on clinical criteria. The aim of this study was to evaluate whether routine C-reactive protein (CRP) and additional inflammatory parameters myeloid-related protein 8/14 (MRP8/14 or S100A8/9) and human neutrophil-derived elastase (HNE) could distinguish KD from infectious diseases. Methods and Results: The cross-sectional study included KD patients and children with proven infections as well as febrile controls. Patients were recruited between July 2006 and December 2018 in Europe and USA. MRP8/14, CRP, and HNE were assessed for their discriminatory ability by multiple logistic regression analysis with backward selection and receiver operator characteristic (ROC) curves. In the discovery cohort, t

Published
2020
Full Text
View/download PDF

34. Mannose-binding lectin and infection risk in newborns: a systematic review

Author

Israel, J., Frakking, F.N.J., Kremer, L.C.M., Offringa, M., Kuijpers, T.W., and van de Wetering, M.D.

Subjects
Mannan-binding lectin -- Measurement, Mannan-binding lectin -- Physiological aspects, Mannan-binding lectin -- Research, Sepsis -- Risk factors, Sepsis -- Demographic aspects, Sepsis -- Research, Biological markers -- Research, Infants (Newborn) -- Diseases, Infants (Newborn) -- Risk factors, Infants (Newborn) -- Diagnosis, Infants (Newborn) -- Research, Family and marriage, Health, Women's issues/gender studies
Published
2010

35. Predictive Performance of Cardiovascular Disease Risk Prediction Algorithms in People Living With HIV

Author

Zoest, R.A. van, Law, M., Sabin, C.A., Vaartjes, I., Valk, M. van der, Arends, J.E., Reiss, P., Wit, F.W., Geerlings, S.E., Godfried, M.H., Goorhuis, A., Hovius, J.W., Kuijpers, T.W., Nellen, F.J.B., Poll, D.T. van der, Prins, J.M., Vugt, H.J.M. van, Wiersinga, W.J., Wit, F.W.M.N., Duinen, M. van, Eden, J. van, Hes, A.M.H. van, Pijnappel, F.J.J., Weijsenfeld, A.M., Jurriaans, S., Back, N.K.T., Zaaijer, H.L., Berkhout, B., Cornelissen, M.T.E., Schinkel, C.J., Wolthers, K.C., Peters, E.J.G., Agtmael, M.A. van, Bomers, M., Heitmuller, M., Laan, L.M., Ang, C.W., Houdt, R. van, Pettersson, A.M., Vandenbroucke-Grauls, C.M.J.E., Berge, M. van den, Stegeman, A., Baas, S., Looff, L.H. de, Wintermans, B., Veenemans, J., Pronk, M.J.H., Ammerlaan, H.S.M., Munnik, E.S. de, Jansz, A.R., Tjhie, J., Wegdam, M.C.A., Deiman, B., Scharnhorst, V., Eeden, A. van, Brokking, W., Groot, M., Elsenburg, L.J.M., Damen, M., Kwa, I.S., Kasteren, M.E.E. van, Brouwer, A.E., Erve, R. van, Kruijf-van de Wiel, B.A.F.M. de, Ven, B. van de, Buiting, A.G.M., Kabel, P.J., Versteeg, D., Ende, M.E. van der, Bax, H.I., Gorp, E.C.M. van, Nouwen, J.L., Rijnders, B.J.A., Schurink, C.A.M., Verbon, A., Vries-Sluijs, T.E.M.S. de, Jong-Peltenburg, N.C. de, Bassant, N., Beek, J.E.A. van, Vriesde, M., Zonneveld, L.M. van, Berg-Cameron, H.J. van den, Groot, J. de, Zeeuw-de Man, M. de, Boucher, C.A.B., Koopmans, M.P.G., Kampen, J.J.A. van, Pas, S.D., Branger, J., Douma, R.A., Duijf-van de Ven, C.J.H.M., Schippers, E.F., Nieuwkoop, C. van, IJperen, J.M. van, Geilings, J., Hut, G. van der, Burgel, N.D. van, Leyten, E.M.S., Gelinck, L.B.S., Davids-Veldhuis, S., Hartingsveld, A.Y. van, Meerkerk, C., Wildenbeest, G.S., Heikens, E., Groeneveld, P.H.P., Bouwhuis, J.W., Lammers, A.J.J., Kraan, S., Hulzen, A.G.W. van, Kruiper, M.S.M., Bliek, G.L. van der, Bor, P.C.J., Bloembergen, P., Wolfhagen, M.J.H.M., Ruijs, G.J.H.M., Kroon, F.P., Boer, M.G.J. de, Scheper, H., Jolink, H., Dorama, W., Holten, N. van, Claas, E.C.J., Wessels, E., Hollander, J.G. den, Pogany, K., Roukens, A., Kastelijns, M., Smit, J.V., Smit, E., Struik-Kalkman, D., Tearno, C., Niekerk, T. van, Pontesilli, O., Lowe, S.H., Lashof, A.M.L.O., Posthouwer, D., Ackens, R.P., Burgers, K., Schippers, J., Weijenberg-Maes, B., Loo, I.H.M. van, Havenith, T.R.A., Mulder, J.W., Vrouenraets, S.M.E., Lauw, F.N., Broekhuizen, M.C. van, Vlasblom, D.J., Smits, P.H.M., Weijer, S., Moussaoui, R. el, Bosma, A.S., Vonderen, M.G.A. van, Kampschreur, L.M., Dijkstra, K., Faber, S., Weel, J., Kootstra, G.J., Delsing, C.E., Burg-van de Plas, M. van der, Heins, H., Kortmann, W., Twillert, G. van, Renckens, R., Ruiter-Pronk, D., Truijen-Oud, F.A. van, Stuart, J.W.T.C., IJzerman, E.P., Jansen, R., Reijden, W.A. van der, Brinkman, K., Berk, G.E.L. van den, Blok, W.L., Frissen, P.H.J., Lettinga, K.D., Schouten, W.E.M., Veenstra, J., Brouwer, C.J., Geerders, G.F., Hoeksema, K., Kleene, M.J., Meche, I.B. van der, Spelbrink, M., Toonen, A.J.M., Wijnands, S., Kwa, D., Regez, R., Crevel, R. van, Keuter, M., Ven, A.J.A.M. van der, Hofstede, H.J.M. ter, Dofferhoff, A.S.M., Hoogerwerf, J., Grintjes-Huisman, K.J.T., Haan, M. de, Marneef, M., Rahamat-Langendoen, J., Stelma, F.F., Burger, D., Gisolf, E.H., Hassing, R.J., Claassen, M., Beest, G. ter, Bentum, P.H.M. van, Langebeek, N., Tiemessen, R., Swanink, C.M.A., Lelyveld, S.F.L. van, Soetekouw, R., Prijt, L.M.M. van der, Swaluw, J. van der, Bermon, N., Herpers, B.L., Veenendaal, D., Verhagen, D.W.M., Wijk, M. van, Bierman, W.F.W., Bakker, M., Kleinnijenhuis, J., Kloeze, E., Stienstra, Y., Wilting, K.R., Wouthuyzen-Bakker, M., Boonstra, A., Meulen, P.A. van der, Weerd, D.A. de, Niesters, H.G.M., Leer-Buter, C.C. van, Knoester, M., Hoepelman, A.I.M., Barth, R.E., Bruns, A.H.W., Ellerbroek, P.M., Mudrikova, T., Oosterheert, J.J., Schadd, E.M., Wassenberg, M.W.M., Zoelen, M.A.D. van, Aarsman, K., Elst-Laurijssen, D.H., Rozemeijer, Graduate School, AII - Infectious diseases, APH - Aging & Later Life, Infectious diseases, Global Health, APH - Digital Health, APH - Personalized Medicine, APH - Global Health, Microbes in Health and Disease (MHD), Neurochirurgie, RS: MHeNs - R3 - Neuroscience, Med Microbiol, Infect Dis & Infect Prev, MUMC+: DA MMI Staf (9), RS: CAPHRI - R4 - Health Inequities and Societal Participation, Internal medicine, Pediatric surgery, Amsterdam Movement Sciences - Rehabilitation & Development, ACS - Diabetes & metabolism, AGEM - Digestive immunity, Medical Microbiology and Infection Prevention, Amsterdam Reproduction & Development (AR&D), Internal Medicine, Virology, and Medical Microbiology & Infectious Diseases

Subjects
Male, Heart disease, Human immunodeficiency virus (HIV), risk prediction algorithms, Blood Pressure, HIV Infections, Disease, 030312 virology, medicine.disease_cause, SUBCLINICAL ATHEROSCLEROSIS, Risk Factors, cardiovascular disease, FRAMINGHAM, Pharmacology (medical), Netherlands, 0303 health sciences, INFECTED PATIENTS, Framingham Risk Score, Middle Aged, Prediction algorithms, Cholesterol, Infectious Diseases, Anti-Retroviral Agents, Cardiovascular Diseases, HUMAN-IMMUNODEFICIENCY-VIRUS, Female, Risk assessment, Algorithms, Adult, Anti-HIV Agents, CARDIOLOGY/AMERICAN HEART ASSOCIATION, HEART-DISEASE, AMERICAN-COLLEGE, DATA-COLLECTION, Risk Assessment, EVENTS, 03 medical and health sciences, SDG 3 - Good Health and Well-being, INFLAMMATION, Environmental health, SCORE, medicine, Humans, Propensity Score, business.industry, HIV, medicine.disease, CD4 Lymphocyte Count, MYOCARDIAL-INFARCTION, Propensity score matching, Disease risk, business
Abstract

Background: People living with HIV (PLWH) experience a higher cardiovascular disease (CVD) risk. Yet, traditional algorithms are often used to estimate CVD risk. We evaluated the performance of 4 commonly used algorithms.Setting: The Netherlands.Methods: We used data from 16,070 PLWH aged > 18 years, who were in care between 2000 and 2016, had no pre-existing CVD, had initiated first combination antiretroviral therapy >1 year ago, and had available data on CD4 count, smoking status, cholesterol, and blood pressure. Predictive performance of 4 algorithms [Data Collection on Adverse Effects of Anti-HIV Drugs Study (D: A: D); Systematic COronary Risk Evaluation adjusted for national data (SCORE-NL); Framingham CVD Risk Score (FRS); and American College of Cardiology and American Heart Association Pooled Cohort Equations (PCE)] was evaluated using a Kaplan-Meier approach. Model discrimination was assessed using Harrell's C-statistic. Calibration was assessed using observed-versusexpected ratios, calibration plots, and Greenwood-Nam-D'Agostino goodness-of-fit tests.Results: All algorithms showed acceptable discrimination (Harrell's C-statistic 0.73-0.79). On a population level, D: A: D, SCORE-NL, and PCE slightly underestimated, whereas FRS slightly overestimated CVD risk (observed-versus-expected ratios 1.35, 1.38, 1.14, and 0.92, respectively). D: A: D, FRS, and PCE best fitted our data but still yielded a statistically significant lack of fit (Greenwood-Nam-D'Agostino chi(2) ranged from 24.57 to 34.22, P Conclusions: All algorithms perform reasonably well in PLWH, with SCORE-NL performing poorest. Prediction algorithms are useful for clinical practice, but clinicians should be aware of their limitations (ie, lack of fit and slight underestimation of CVD risk in low-risk groups).

Published
2019
Full Text
View/download PDF

37. Potentiation of complement regulator factor H protects human endothelial cells from complement attack in aHUS sera

Author

Pouw, R.B., Brouwer, M.C.T., Gast, M. de, Beek, A.E. van, Heuvel, L.P.W.J. van den, Schmidt, C.Q., Ende, A. van der, Sanchez-Corral, P., Kuijpers, T.W., Wouters, D., Pouw, R.B., Brouwer, M.C.T., Gast, M. de, Beek, A.E. van, Heuvel, L.P.W.J. van den, Schmidt, C.Q., Ende, A. van der, Sanchez-Corral, P., Kuijpers, T.W., and Wouters, D.

Abstract

Contains fulltext : 202685.pdf (publisher's version ) (Open Access), Mutations in the gene encoding for complement regulator factor H (FH) severely disrupt its normal function to protect human cells from unwanted complement activation, resulting in diseases such as atypical hemolytic uremic syndrome (aHUS). aHUS presents with severe hemolytic anemia, thrombocytopenia, and renal disease, leading to end-stage renal failure. Treatment of severe complement-mediated disease, such as aHUS, by inhibiting the terminal complement pathway, has proven to be successful but at the same time fails to preserve the protective role of complement against pathogens. To improve complement regulation on human cells without interfering with antimicrobial activity, we identified an anti-FH monoclonal antibody (mAb) that induced increased FH-mediated protection of primary human endothelial cells from complement, while preserving the complement-mediated killing of bacteria. Moreover, this FH-activating mAb restored complement regulation in sera from aHUS patients carrying various heterozygous mutations in FH known to impair FH function and dysregulate complement activation. Our data suggest that FH normally circulates in a less active conformation and can become more active, allowing enhanced complement regulation on human cells. Antibody-mediated potentiation of FH may serve as a highly effective approach to inhibit unwanted complement activation on human cells in a wide range of hematological diseases while preserving the protective role of complement against pathogens.

Published
2019

38. Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Author

Borghini, L., Png, E., Binder, A., Wright, V.J., Pinnock, E., Groot, R. de, Hazelzet, J., Emonts, M., Flier, M. van der, Philipsen, H.L.A., Schlapbach, L.J., Anderson, S., Secka, F., Salas, A., Fink, C., Carrol, E.D., Pollard, A.J., Coin, L.J., Kuijpers, T.W., Martinon-Torres, F., Zenz, W., Levin, M., Hibberd, M.L., Davila, S., Neeleman, C., Deuren, M. van, Kunze, W., Schermann, P., Borghini, L., Png, E., Binder, A., Wright, V.J., Pinnock, E., Groot, R. de, Hazelzet, J., Emonts, M., Flier, M. van der, Philipsen, H.L.A., Schlapbach, L.J., Anderson, S., Secka, F., Salas, A., Fink, C., Carrol, E.D., Pollard, A.J., Coin, L.J., Kuijpers, T.W., Martinon-Torres, F., Zenz, W., Levin, M., Hibberd, M.L., Davila, S., Neeleman, C., Deuren, M. van, Kunze, W., and Schermann, P.

Abstract

Contains fulltext : 204148.pdf (publisher's version ) (Open Access), Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes.

Published
2019

39. No radiographic wrist damage after treatment to target in recent-onset juvenile idiopathic arthritis

Author

Muller, P., van Braak, W.G., Schreurs, D., Nusman, C.M., Bergstra, S.A., Hemke, R., Schonenberg-Meinema, D., van den Berg, J.M., Kuijpers, T.W. (Taco W.), Koopman-Keemink, Y. (Yvonne), Rossum, M.A. (Maya) van, Suijlekom-Smit, L.W.A. (Lisette) van, Brinkman, D.M.C., Allaart, C.F. (Cornelia), Cate, R. (Rebecca) ten, Maas, M, Muller, P., van Braak, W.G., Schreurs, D., Nusman, C.M., Bergstra, S.A., Hemke, R., Schonenberg-Meinema, D., van den Berg, J.M., Kuijpers, T.W. (Taco W.), Koopman-Keemink, Y. (Yvonne), Rossum, M.A. (Maya) van, Suijlekom-Smit, L.W.A. (Lisette) van, Brinkman, D.M.C., Allaart, C.F. (Cornelia), Cate, R. (Rebecca) ten, and Maas, M

Abstract

Background: To evaluate radiographic progression of patients with new-onset juvenile idiopathic arthritis (JIA) in response to an early, tightly-controlled, treatment-to-target. Methods: Patients with JIA participating in the BeSt-for-Kids-study, randomized to 3 treatment strategy arms, were eligible if at least 1 conventional wrist-radiograph was available. Bone damage as reflected by carpal length was assessed using the Poznanski-score. The BoneXpert-method was used to determine the Bone Age (BA, > 5 years) and bone mineral density (BMD) of the wrist. These scores were evaluated over time and compared between the treatment arms and mean JADAS10-score using linear mixed models corrected for age and symptom duration. Results: In 60 patients, 252 radiographs were analysed. Baseline age and symptom duration were different between the arms. No difference in comparison to the healthy reference population was found at baseline for the Poznanskiscore (IQR varying from − 0,82; 0.68), nor for BA (varying from − 0.88 to 0.74). Baseline BMD was statistically significantly lower in arm 3 (initial treatment with etanercept and methotrexate) (− 1.48; − 0.68) compared to

Published
2019
Full Text
View/download PDF

40. Short-limbed dwarfism with bowing, combined immune deficiency, and late onset aplastic anaemia caused by novel mutations in the RMPR gene

Author

Kuijpers, T.W., Ridanpaa, M., Peters, M., De Boer, I., Vossen, J.M.J.J., Pals, S.T., Kaitila, I., and Hennekam, R.C.M.

Subjects
Gene mutations -- Physiological aspects -- Health aspects -- Research -- Analysis -- Genetic aspects, Genetic research -- Analysis -- Physiological aspects -- Genetic aspects -- Health aspects, Dysplasia -- Health aspects -- Genetic aspects -- Complications and side effects -- Research, Medical genetics -- Research -- Health aspects -- Analysis -- Physiological aspects, Dwarfism -- Genetic aspects -- Health aspects -- Causes of -- Research -- Complications and side effects, Health
Abstract

J Med Genet 2003;40:761-766 Kyphomelic dysplasia has been described as a generalised skeletal dysplasia characterised by a disproportionate growth, bowing of long bones, mild facial dysmorphia, and normal intelligence, with [...]

Published
2003

41. Neutrophil migration across monolayers of cytokine-prestimulated endothelialcells: a role for platelet-activating factor and IL-8

Author

Kuijpers, T.W., Hakkert, B.C., Hart, M.H.L., and Roos, D.

Subjects
Platelet activating factor -- Research, Neutrophils -- Research, Interleukins -- Research, Cell migration -- Research, Biological sciences
Abstract

The roles of endothelial cell (EC) membrane-associated platelet- activating factor (PAF) and interleukin-8 (IL-8) in neutrophil migration acrossmonolayers of cytokine-activated EC were investigated. Using PAF receptor antagonists and anti-IL-8 antiserum, the study showed that the in vitro migration of human neutrophils in cytokine-activated monolayers of human EC is activated and guided by EC membrane-associated PAF and EC-derived IL-8.

Published
1992

42. Loss-of-function nuclear factor κB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans

Author

Tuijnenburg, P., Lango Allen, H., Burns, S.O., Greene, D., Jansen, M.H., Staples, E., Stephens, J., Carss, K.J., Biasci, D., Baxendale, H., Thomas, M., Chandra, A., Kiani-Alikhan, S., Longhurst, H.J., Seneviratne, S.L., Oksenhendler, E., Simeoni, I., de Bree, G.J., Tool, A.T.J., van Leeuwen, E.M.M., Ebberink, E.H.T.M., Meijer, A.B., Tuna, S., Whitehorn, D., Brown, M., Turro, E., Thrasher, A.J., Smith, K.G.C., Thaventhiran, J.E., Kuijpers, T.W., Adhya, Z., Alachkar, H., Anantharachagan, A., Antrobus, R., Arumugakani, G., Bacchelli, C., Bethune, C., Bibi, S., Boardman, B., Booth, C., Browning, M., Brownlie, M., Burns, S., Clifford, H., Cooper, N., Davies, S., Dempster, J., Devlin, L., Doffinger, R., Drewe, E., Edgar, D., Egner, W., El-Shanawany, T., Gaspar, B., Ghurye, R., Gilmour, K., Goddard, S., Gordins, P., Grigoriadou, S., Hackett, S., Hague, R., Harper, L., Hayman, G., Herwadkar, A., Hughes, S., Huissoon, A., Jolles, S., Jones, J., Kelleher, P., Klein, N., Kuijpers, T., Kumararatne, D., Laffan, J., Allen, H.L., Lear, S., Longhurst, H., Lorenzo, L., Maimaris, J., Manson, A., McDermott, E., Millar, H., Mistry, A., Morrisson, V., Murng, S., Nasir, I., and Nejentsev, S.

Abstract

Background: The genetic cause of primary immunodeficiency disease (PID) carries prognostic information. Objective: We conducted a whole-genome sequencing study assessing a large proportion of the NIHR BioResource–Rare Diseases cohort. Methods: In the predominantly European study population of principally sporadic unrelated PID cases (n = 846), a novel Bayesian method identified nuclear factor κB subunit 1 (NFKB1) as one of the genes most strongly associated with PID, and the association was explained by 16 novel heterozygous truncating, missense, and gene deletion variants. This accounted for 4% of common variable immunodeficiency (CVID) cases (n = 390) in the cohort. Amino acid substitutions predicted to be pathogenic were assessed by means of analysis of structural protein data. Immunophenotyping, immunoblotting, and ex vivo stimulation of lymphocytes determined the functional effects of these variants. Detailed clinical and pedigree information was collected for genotype-phenotype cosegregation analyses. Results: Both sporadic and familial cases demonstrated evidence of the noninfective complications of CVID, including massive lymphadenopathy (24%), unexplained splenomegaly (48%), and autoimmune disease (48%), features prior studies correlated with worse clinical prognosis. Although partial penetrance of clinical symptoms was noted in certain pedigrees, all carriers have a deficiency in B-lymphocyte differentiation. Detailed assessment of B-lymphocyte numbers, phenotype, and function identifies the presence of an increased CD21lowB-cell population. Combined with identification of the disease-causing variant, this distinguishes between healthy subjects, asymptomatic carriers, and clinically affected cases. Conclusion: We show that heterozygous loss-of-function variants in NFKB1 are the most common known monogenic cause of CVID, which results in a temporally progressive defect in the formation of immunoglobulin-producing B cells.

Published
2018

43. Dynamics of Transcription Regulation in Human Bone Marrow Myeloid Differentiation to Mature Blood Neutrophils.

Author

Grassi, L., Pourfarzad, F., Ullrich, S., Merkel, A., Were, F., Carrillo-de-Santa-Pau, E., Yi, G., Hiemstra, I.H., Tool, A.T., Mul, E., Perner, J., Janssen-Megens, E.M., Berentsen, K., Kerstens, H.H.D., Habibi, E., Gut, M., Yaspo, M.L., Linser, M., Lowy, E., Datta, A., Clarke, L., Flicek, P., Vingron, M., Roos, D., Berg, T.K. van den, Heath, S., Rico, D., Frontini, M., Kostadima, M., Gut, I., Valencia, A., Ouwehand, W.H., Stunnenberg, H., Martens, J.H.A., Kuijpers, T.W., Grassi, L., Pourfarzad, F., Ullrich, S., Merkel, A., Were, F., Carrillo-de-Santa-Pau, E., Yi, G., Hiemstra, I.H., Tool, A.T., Mul, E., Perner, J., Janssen-Megens, E.M., Berentsen, K., Kerstens, H.H.D., Habibi, E., Gut, M., Yaspo, M.L., Linser, M., Lowy, E., Datta, A., Clarke, L., Flicek, P., Vingron, M., Roos, D., Berg, T.K. van den, Heath, S., Rico, D., Frontini, M., Kostadima, M., Gut, I., Valencia, A., Ouwehand, W.H., Stunnenberg, H., Martens, J.H.A., and Kuijpers, T.W.

Abstract

Contains fulltext : 195014.pdf (publisher's version ) (Open Access), Neutrophils are short-lived blood cells that play a critical role in host defense against infections. To better comprehend neutrophil functions and their regulation, we provide a complete epigenetic overview, assessing important functional features of their differentiation stages from bone marrow-residing progenitors to mature circulating cells. Integration of chromatin modifications, methylation, and transcriptome dynamics reveals an enforced regulation of differentiation, for cellular functions such as release of proteases, respiratory burst, cell cycle regulation, and apoptosis. We observe an early establishment of the cytotoxic capability, while the signaling components that activate these antimicrobial mechanisms are transcribed at later stages, outside the bone marrow, thus preventing toxic effects in the bone marrow niche. Altogether, these data reveal how the developmental dynamics of the chromatin landscape orchestrate the daily production of a large number of neutrophils required for innate host defense and provide a comprehensive overview of differentiating human neutrophils.

Published
2018

44. High treatment uptake in human immunodeficiency virus/ hepatitis C virus-coinfected patients after unrestricted access to direct-acting antivirals in the Netherlands

Author

Boerekamps, A. (Anne), Newsum, A.M. (Astrid M.), Smit, C. (Colette), Arends, J.E. (Joop), Richter, C. (Clemens), Reiss, P. (Peter), Rijnders, B.J.A. (Bart), Brinkman, K. (Kees), Valk, M. (Marc) van der, Geerlings, S.E. (Suzanne), Godfried, M.H., Goorhuis, A. (Abraham), Hovius, J.W.R. (Joppe), Meer, J.T.M. (J. T M) van der, Kuijpers, T.W. (Taco W.), Nellen, F.J.B. (F. J B), Van Der Poll, D.T. (D. T.), Prins, J.M. (Jan), Van Vugt, H.J.M. (H. J.M.), Wiersinga, W.J. (W. J.), Wit, F.W.N.M. (Ferdinand), Van Duinen, M. (M.), Van Eden, J., Van Hes, A.M.H., Mutschelknauss, M., Nobel, H.E., Pijnappel, F.J.J., Weijsenfeld, A.M., Jurriaans, S. (Suzanne), Back, N. (Nicole), Zaaijer, H.L. (Hans), Berkhout, B. (Ben), Cornelissen, M. (Marion), Schinkel, C.J., Wolthers, K.C. (Katja), Van Den Berge, M., Stegeman, A., Baas, S., Hage De Looff, L. (L.), Wintermans, B. (B.), Veenemans, J. (J.), Pronk, M.J.H. (Marjolijn), Ammerlaan, H.S.M. (Heidi), De Munnik, E.S., Jansz, A.R. (A. R.), Tjhie, J. (J.), Wegdam, M.C.A., Deiman, B. (B.), Scharnhorst, V., Eeden, A. (Arne) van, Brokking, W. (W.), Groot, M.M. (Marieke), Elsenburg, L.J.M. (L. J.M.), Damen, M. (M.), Kwa, I.S., Kasteren, M.E.E. (Marjo) van, Brouwer, A.E., Van Erve, R. (R.), De Kruijf-Van De Wiel, B.A.F.M. (B. A.F.M.), Keelan-Pfaf, S. (S.), Van Der Ven, B. (B.), Van Der Ven, B., Buiting, A.G.M. (Anton), Kabel, P.J. (P. J.), Versteeg, D., Ende, M.E. (Marchina) van der, Bax, H.I. (Hannelore), Gorp, E.C.M. (Eric) van, Nouwen, J.L. (Jan), Schurink, C.A.M. (Carolina), Verbon, A. (Annelies), Vriessluijs, T.E.M.S. (Theodora) de, De Jong-Peltenburg, N.C. (N. C.), Bassant, N., Van Beek, J.E.A., Vriesde, M., van Zonneveld, L. (Laura), Van Den Berg-Cameron, H.J., Groot, J.C. (Jan Cees) de, De Zeeuw-De Man, M., Boucher, C.A.B. (Charles), Koopmans D.V.M., M.P.G. (Marion), Kampen, J.J.A. (Jeroen) van, Pas, S.D. (Suzan), Branger, J., Rijkeboer-Mes, A. (A.), Duijf-Van De Ven, C.J.H.M., Schippers, E.F. (E. F.), Nieuwkoop, C. (Cees) van, Van IJperen, J.M. (J. M.), Geilings, J. (J.), Van Der Hut, G., Burgel, N.D. (Nathalie ) van, Leyten, E.M.S. (Eliane), Gelinck, L.B.S. (Luc), Van Hartingsveld, A.Y. (A. Y.), Meerkerk, C., Wildenbeest, G.S., Heikens, E. (E.), Groeneveld, P.H.P. (P. H.P.), Bouwhuis, J.W. (Jolande), Lammers, A.J.J. (A. J.J.), Kraan, S. (S.), Van Hulzen, A.G.W., Van Der Bliek, G.L. (G. L.), Bor, P.C.J., Bloembergen, P. (Peter), Wolfhagen, M.J.H.M., Ruijs, G. (G.), Kroon, F.P. (F. P.), Boer, M.G.J. (Mark) de, Scheper, H. (H.), Jolink, A. (Albert), Vollaard, A. (Albert), Dorama, W. (Willemien), Van Holten, N. (N.), Claas, E.C.J. (Eric), Wessels, E. (E.), Hollander, J.G. (Jan) den, Pogány, K. (Katalin), Roukens, A. (A.), Kastelijns, M. (M.), Smit, J.V., Smit, E., Struik-Kalkman, D. (D.), Tearno, C. (C.), Van Niekerk, T., Pontesilli, O. (Oscar), Lowe, S.H. (S. H.), Oude Lashof, A. (A.), Posthouwer, D. (Dirk), Ackens, R.P. (R. P.), Burgers, K. (K.), Schippers, J., Weijenberg-Maes, B. (B.), Loo, I. (Inge) van, Havenith, T., Mulder, J.W. (J. W.), Vrouenraets, B.C. (Bart), Lauw, F.N. (F. N.), van Broekhuizen, M. (Marjolein), Vlasblom, D.J., Smits, P.H.M. (Paul), Weijer, S. (S.), El Moussaoui, R., Bosma, A.S. (A. S.), Vonderen, M.G.A. van, Van Houte, D.P.F., Kampschreur, L.M., Dijkstra, K. (K.), Faber, S., Weel, J. (J.), Kootstra, J.G. (Jille), Delsing, C.E. (C. E.), Van Der Burg-Van De Plas, M. (M.), Heins, H., Lucas, E. (E.), Kortmann, B., Van Twillert, G. (G.), Renckens, R. (Rosemarijn), Ruiter-Pronk, D. (D.), Van Truijen-Oud, F.A., Cohen Stuart, J.W.T. (James), IJzerman, E.P.F. (Ed), Jansen, R.J. (Roel), Rozemeijer, W. (Wouter), Van Der Reijden, W.A. (W. A.), Berk, G.E.L. (Guido) van den, Blok, W.L. (Willem), Frissen, P.H.J., Lettinga, K.D. (Kamilla), Schouten, W.E.M.I. (Ineke), Veenstra, J. (Jan), Brouwer, C.J., Geerders, G.F., Hoeksema, K., Kleene, M.J., Van Der Meché, I.B., Spelbrink, M. (M.), Toonen, A.J.M., Wijnands, S. (S.), Kwa, S.L.S. (Stefan), Regez, R.M. (Rosa), Crevel, R. (Reinout) van, Keuter, M. (Monique), Ven, A.D. (Andre´) van, Ter Hofstede, H.J.M. (H. J.M.), Dofferhoff, A.S.M. (Anton), Hoogerwerf, J. (J.), Grintjes-Huisman, K.J.T., De Haan, M. (M.), Marneef, M. (M.), Hairwassers, A. (A.), Rahamat-Langendoen, J. (J.), Stelma, F.F. (Foekje), Burger, D.M. (David), Gisolf, E.H. (Elisabeth), Hassing, R.J. (Robert), Claassen, M.A.A. (Mark), Ter Beest, G. (G.), Van Bentum, P.H.M., Langebeek, N. (Nienke), Tiemessen, R. (R.), Swanink, C. (Caroline), Lelyveld, S.F.L. van, Soetekouw, R. (Robert), Van Der Prijt, L.M.M., Van Der Swaluw, J. (J.), Bermon, N. (N.), Jansen, R. (R.), Herpers, B.L. (B. L.), Veenendaal, D. (Dick), Verhagen, D.W.M. (Dominique), Van Wijk, M. (M.), Bierman, W.F.W. (Wouter), Bakker, M. (M.), Kleinnijenhuis, J. (J.), Kloeze, E. (E.), Stienstra, Y. (Y.), Wilting, K.R., Wouthuyzen-Bakker, M. (Marjan), Boonstra, P.A. (André), Van Der Meulen, P.A., De Weerd, D.A., Niesters, H.G.M. (Bert), Van Leer-Buter, C. (Coretta), Knoester, M. (M.), Hoepelman, I.M. (Ilja Mohandas), Barth, R.E. (R. E.), Bruns, A.H.W. (A. H.W.), Ellerbroek, P.M. (P.), Mudrikova, T. (Tania Tania), Oosterheert, J.J. (Jan Jelrik), Schadd, E.M. (E. M.), Wassenberg, M.W.M., Van Zoelen, M.A.D. (M. A.D.), Aarsman, K. (K.), Van Elst-Laurijssen, D.H.M. (D. H.M.), De Kroon, I. (I.), Van Rooijen, C.S.A.M. (C. S.A.M.), Van Berkel, M. (M.), Schuurman, R. (Rob), Verduyn-Lunel, F., Wensing, A. (Amj), Peters, E.J.G., Van Agtmael, M.A. (M. A.), Bomers, M., Heitmuller, M. (M.), Laan, L.M., Ang, C.W. (Wim), Houdt, R. van, Pettersson, A. (Annika), Vandenbroucke-Grauls, C.M.J.E. (Christina), Bezemer, D.O. (Daniela), Sighem, A.I. (Ard) van, Smit, C. (Cees), Wit, F. (Ferdinand), Boender, T.S. (T. S.), Zaheri, S. (S.), Hillebregt, M.M.J. (Mariska), De Jong, A., Bergsma, D., Grivell, S., Jansen, A. (A.), Raethke, M., Meijering, R., Rutkens, T. (T.), De Groot, L. (L.), Van Den Akker, M. (M.), Bakker, Y., Bezemer, M. (M.), Claessen, E., El Berkaoui, A. (A.), Geerlinks, J. (J.), Koops, J. (J.), Kruijne, E., Lodewijk, C., Van Der Meer, R. (R.), Munjishvili, L., Paling, F. (F.), Peeck, B., Ree, C., Regtop, R., Ruijs, Y., Schoorl, M. (Marianne), Timmerman, A. (A.), Tuijn, E., Veenenberg, L., Van Der Vliet, S. (S.), Wisse, A. (A.), De Witte, E.C. (E. C.), Woudstra, T., Tuk, B. (B.), Boerekamps, A. (Anne), Newsum, A.M. (Astrid M.), Smit, C. (Colette), Arends, J.E. (Joop), Richter, C. (Clemens), Reiss, P. (Peter), Rijnders, B.J.A. (Bart), Brinkman, K. (Kees), Valk, M. (Marc) van der, Geerlings, S.E. (Suzanne), Godfried, M.H., Goorhuis, A. (Abraham), Hovius, J.W.R. (Joppe), Meer, J.T.M. (J. T M) van der, Kuijpers, T.W. (Taco W.), Nellen, F.J.B. (F. J B), Van Der Poll, D.T. (D. T.), Prins, J.M. (Jan), Van Vugt, H.J.M. (H. J.M.), Wiersinga, W.J. (W. J.), Wit, F.W.N.M. (Ferdinand), Van Duinen, M. (M.), Van Eden, J., Van Hes, A.M.H., Mutschelknauss, M., Nobel, H.E., Pijnappel, F.J.J., Weijsenfeld, A.M., Jurriaans, S. (Suzanne), Back, N. (Nicole), Zaaijer, H.L. (Hans), Berkhout, B. (Ben), Cornelissen, M. (Marion), Schinkel, C.J., Wolthers, K.C. (Katja), Van Den Berge, M., Stegeman, A., Baas, S., Hage De Looff, L. (L.), Wintermans, B. (B.), Veenemans, J. (J.), Pronk, M.J.H. (Marjolijn), Ammerlaan, H.S.M. (Heidi), De Munnik, E.S., Jansz, A.R. (A. R.), Tjhie, J. (J.), Wegdam, M.C.A., Deiman, B. (B.), Scharnhorst, V., Eeden, A. (Arne) van, Brokking, W. (W.), Groot, M.M. (Marieke), Elsenburg, L.J.M. (L. J.M.), Damen, M. (M.), Kwa, I.S., Kasteren, M.E.E. (Marjo) van, Brouwer, A.E., Van Erve, R. (R.), De Kruijf-Van De Wiel, B.A.F.M. (B. A.F.M.), Keelan-Pfaf, S. (S.), Van Der Ven, B. (B.), Van Der Ven, B., Buiting, A.G.M. (Anton), Kabel, P.J. (P. J.), Versteeg, D., Ende, M.E. (Marchina) van der, Bax, H.I. (Hannelore), Gorp, E.C.M. (Eric) van, Nouwen, J.L. (Jan), Schurink, C.A.M. (Carolina), Verbon, A. (Annelies), Vriessluijs, T.E.M.S. (Theodora) de, De Jong-Peltenburg, N.C. (N. C.), Bassant, N., Van Beek, J.E.A., Vriesde, M., van Zonneveld, L. (Laura), Van Den Berg-Cameron, H.J., Groot, J.C. (Jan Cees) de, De Zeeuw-De Man, M., Boucher, C.A.B. (Charles), Koopmans D.V.M., M.P.G. (Marion), Kampen, J.J.A. (Jeroen) van, Pas, S.D. (Suzan), Branger, J., Rijkeboer-Mes, A. (A.), Duijf-Van De Ven, C.J.H.M., Schippers, E.F. (E. F.), Nieuwkoop, C. (Cees) van, Van IJperen, J.M. (J. M.), Geilings, J. (J.), Van Der Hut, G., Burgel, N.D. (Nathalie ) van, Leyten, E.M.S. (Eliane), Gelinck, L.B.S. (Luc), Van Hartingsveld, A.Y. (A. Y.), Meerkerk, C., Wildenbeest, G.S., Heikens, E. (E.), Groeneveld, P.H.P. (P. H.P.), Bouwhuis, J.W. (Jolande), Lammers, A.J.J. (A. J.J.), Kraan, S. (S.), Van Hulzen, A.G.W., Van Der Bliek, G.L. (G. L.), Bor, P.C.J., Bloembergen, P. (Peter), Wolfhagen, M.J.H.M., Ruijs, G. (G.), Kroon, F.P. (F. P.), Boer, M.G.J. (Mark) de, Scheper, H. (H.), Jolink, A. (Albert), Vollaard, A. (Albert), Dorama, W. (Willemien), Van Holten, N. (N.), Claas, E.C.J. (Eric), Wessels, E. (E.), Hollander, J.G. (Jan) den, Pogány, K. (Katalin), Roukens, A. (A.), Kastelijns, M. (M.), Smit, J.V., Smit, E., Struik-Kalkman, D. (D.), Tearno, C. (C.), Van Niekerk, T., Pontesilli, O. (Oscar), Lowe, S.H. (S. H.), Oude Lashof, A. (A.), Posthouwer, D. (Dirk), Ackens, R.P. (R. P.), Burgers, K. (K.), Schippers, J., Weijenberg-Maes, B. (B.), Loo, I. (Inge) van, Havenith, T., Mulder, J.W. (J. W.), Vrouenraets, B.C. (Bart), Lauw, F.N. (F. N.), van Broekhuizen, M. (Marjolein), Vlasblom, D.J., Smits, P.H.M. (Paul), Weijer, S. (S.), El Moussaoui, R., Bosma, A.S. (A. S.), Vonderen, M.G.A. van, Van Houte, D.P.F., Kampschreur, L.M., Dijkstra, K. (K.), Faber, S., Weel, J. (J.), Kootstra, J.G. (Jille), Delsing, C.E. (C. E.), Van Der Burg-Van De Plas, M. (M.), Heins, H., Lucas, E. (E.), Kortmann, B., Van Twillert, G. (G.), Renckens, R. (Rosemarijn), Ruiter-Pronk, D. (D.), Van Truijen-Oud, F.A., Cohen Stuart, J.W.T. (James), IJzerman, E.P.F. (Ed), Jansen, R.J. (Roel), Rozemeijer, W. (Wouter), Van Der Reijden, W.A. (W. A.), Berk, G.E.L. (Guido) van den, Blok, W.L. (Willem), Frissen, P.H.J., Lettinga, K.D. (Kamilla), Schouten, W.E.M.I. (Ineke), Veenstra, J. (Jan), Brouwer, C.J., Geerders, G.F., Hoeksema, K., Kleene, M.J., Van Der Meché, I.B., Spelbrink, M. (M.), Toonen, A.J.M., Wijnands, S. (S.), Kwa, S.L.S. (Stefan), Regez, R.M. (Rosa), Crevel, R. (Reinout) van, Keuter, M. (Monique), Ven, A.D. (Andre´) van, Ter Hofstede, H.J.M. (H. J.M.), Dofferhoff, A.S.M. (Anton), Hoogerwerf, J. (J.), Grintjes-Huisman, K.J.T., De Haan, M. (M.), Marneef, M. (M.), Hairwassers, A. (A.), Rahamat-Langendoen, J. (J.), Stelma, F.F. (Foekje), Burger, D.M. (David), Gisolf, E.H. (Elisabeth), Hassing, R.J. (Robert), Claassen, M.A.A. (Mark), Ter Beest, G. (G.), Van Bentum, P.H.M., Langebeek, N. (Nienke), Tiemessen, R. (R.), Swanink, C. (Caroline), Lelyveld, S.F.L. van, Soetekouw, R. (Robert), Van Der Prijt, L.M.M., Van Der Swaluw, J. (J.), Bermon, N. (N.), Jansen, R. (R.), Herpers, B.L. (B. L.), Veenendaal, D. (Dick), Verhagen, D.W.M. (Dominique), Van Wijk, M. (M.), Bierman, W.F.W. (Wouter), Bakker, M. (M.), Kleinnijenhuis, J. (J.), Kloeze, E. (E.), Stienstra, Y. (Y.), Wilting, K.R., Wouthuyzen-Bakker, M. (Marjan), Boonstra, P.A. (André), Van Der Meulen, P.A., De Weerd, D.A., Niesters, H.G.M. (Bert), Van Leer-Buter, C. (Coretta), Knoester, M. (M.), Hoepelman, I.M. (Ilja Mohandas), Barth, R.E. (R. E.), Bruns, A.H.W. (A. H.W.), Ellerbroek, P.M. (P.), Mudrikova, T. (Tania Tania), Oosterheert, J.J. (Jan Jelrik), Schadd, E.M. (E. M.), Wassenberg, M.W.M., Van Zoelen, M.A.D. (M. A.D.), Aarsman, K. (K.), Van Elst-Laurijssen, D.H.M. (D. H.M.), De Kroon, I. (I.), Van Rooijen, C.S.A.M. (C. S.A.M.), Van Berkel, M. (M.), Schuurman, R. (Rob), Verduyn-Lunel, F., Wensing, A. (Amj), Peters, E.J.G., Van Agtmael, M.A. (M. A.), Bomers, M., Heitmuller, M. (M.), Laan, L.M., Ang, C.W. (Wim), Houdt, R. van, Pettersson, A. (Annika), Vandenbroucke-Grauls, C.M.J.E. (Christina), Bezemer, D.O. (Daniela), Sighem, A.I. (Ard) van, Smit, C. (Cees), Wit, F. (Ferdinand), Boender, T.S. (T. S.), Zaheri, S. (S.), Hillebregt, M.M.J. (Mariska), De Jong, A., Bergsma, D., Grivell, S., Jansen, A. (A.), Raethke, M., Meijering, R., Rutkens, T. (T.), De Groot, L. (L.), Van Den Akker, M. (M.), Bakker, Y., Bezemer, M. (M.), Claessen, E., El Berkaoui, A. (A.), Geerlinks, J. (J.), Koops, J. (J.), Kruijne, E., Lodewijk, C., Van Der Meer, R. (R.), Munjishvili, L., Paling, F. (F.), Peeck, B., Ree, C., Regtop, R., Ruijs, Y., Schoorl, M. (Marianne), Timmerman, A. (A.), Tuijn, E., Veenenberg, L., Van Der Vliet, S. (S.), Wisse, A. (A.), De Witte, E.C. (E. C.), Woudstra, T., and Tuk, B. (B.)

Abstract

Background The Netherlands has provided unrestricted access to direct-acting antivirals (DAAs) since November 2015. We analyzed the nationwide hepatitis C virus (HCV) treatment uptake among patients coinfected with human immunodeficiency virus (HIV) and HCV. Methods Data were obtained from the ATHENA HIV observational cohort in which >98% of HIV-infected patients ever registered since 1998 are included. Patients were included if they ever had 1 positive HCV RNA result, did not have spontaneous clearance, and were known to still be in care. Treatment uptake and outcome were assessed. When patients were treated more than once, data were included from only the most recent treatment episode. Data were updated until February 2017. In addition, each treatment center was queried in April 2017 for a data update on DAA treatment and achieved sustained virological response. Results Of 23574 HIV-infected patients ever linked to care, 1471 HCV-coinfected patients (69% men who have sex with men, 15% persons who [formerly] injected drugs, and 15% with another HIV transmission route) fulfilled the inclusion criteria. Of these, 87% (1284 of 1471) had ever initiated HCV treatment between 2000 and 2017, 76% (1124 of 1471) had their HCV infection cured; DAA treatment results were pending in 6% (92 of 1471). Among men who have sex with men, 83% (844 of 1022) had their HCV infection cured, and DAA treatment results were pending in 6% (66 of 1022). Overall, 187 patients had never initiated treatment, DAAs had failed in 14, and a pegylated interferon-alfa–based regimen had failed in 54. Conclusions Fifteen months after unrestricted DAA availability the majority of HIV/HCV-coinfected patients in the Netherlands have their HCV infection cured (76%) or are awaiting DAA treatment results (6%). This rapid treatment scale-up may contribute to future HCV elimination among these patients.

Published
2018
Full Text
View/download PDF

46. Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types

Author

Ecker, S., Chen, L., Pancaldi, V., Bagger, F.O., Fernandez, J.M., Carrillo de Santa Pau, E., Juan, D., Mann, A.L., Watt, S., Casale, F.P., Sidiropoulos, N., Rapin, N., Merkel, A., Stunnenberg, H., Stegle, O., Frontini, M., Downes, K., Pastinen, T., Kuijpers, T.W., Rico, D., Valencia, A., Beck, S., Soranzo, N., Paul, D.S., and Albers, C.A.

Subjects
Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Molecular Biology
Abstract

Contains fulltext : 169675.pdf (Publisher’s version ) (Open Access) BACKGROUND: A healthy immune system requires immune cells that adapt rapidly to environmental challenges. This phenotypic plasticity can be mediated by transcriptional and epigenetic variability. RESULTS: We apply a novel analytical approach to measure and compare transcriptional and epigenetic variability genome-wide across CD14+CD16- monocytes, CD66b+CD16+ neutrophils, and CD4+CD45RA+ naive T cells from the same 125 healthy individuals. We discover substantially increased variability in neutrophils compared to monocytes and T cells. In neutrophils, genes with hypervariable expression are found to be implicated in key immune pathways and are associated with cellular properties and environmental exposure. We also observe increased sex-specific gene expression differences in neutrophils. Neutrophil-specific DNA methylation hypervariable sites are enriched at dynamic chromatin regions and active enhancers. CONCLUSIONS: Our data highlight the importance of transcriptional and epigenetic variability for the key role of neutrophils as the first responders to inflammatory stimuli. We provide a resource to enable further functional studies into the plasticity of immune cells, which can be accessed from: http://blueprint-dev.bioinfo.cnio.es/WP10/hypervariability .

Published
2017

49. THU0579 Validation of contrast-enhanced mri scores on (TENO)synovitis of the wrist in juvenile idiopathic arthritispatients by comparison with children unaffected by clinical arthritis

Author

Van Der Krogt, J.M., primary, van Gulik, E.C., additional, Hemke, R., additional, van den Berg, J.M., additional, Schonenberg, D., additional, Kindermann, A., additional, Dolman, K.M., additional, Benninga, M.A., additional, Kuijpers, T.W., additional, Maas, M., additional, and Nusman, C.M., additional

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results