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23 results on '"Skipp, P. J."'

2. A novel ACE2 isoform is expressed in human respiratory epithelia and is upregulated in response to interferons and RNA respiratory virus infection

Author

Blume, Cornelia, Jackson, Claire L., Spalluto, Cosma Mirella, Legebeke, Jelmer, Nazlamova, Liliya, Conforti, Franco, Perotin, Jeanne-Marie, Frank, Martin, Butler, John, Crispin, Max, Coles, Janice, Thompson, James, Ridley, Robert A., Dean, Lareb S. N., Loxham, Matthew, Reikine, Stephanie, Azim, Adnan, Tariq, Kamran, Johnston, David A., Skipp, Paul J., Djukanovic, Ratko, Baralle, Diana, McCormick, Christopher J., Davies, Donna E., Lucas, Jane S., Wheway, Gabrielle, and Mennella, Vito

Published
2021
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4. Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation

Author

Mikus, M. S., Kolmert, J., Andersson, L. I., Ostling, J., Knowles, R. G., Gomez, C., Ericsson, M., Thorngren, J. -O., Khoonsari, P. E., Dahlen, B., Kupczyk, M., de Meulder, B., Auffray, C., Bakke, P. S., Beghe, Bianca, Bel, E. H., Caruso, M., Chanez, P., Chawes, B., Fowler, S. J., Gaga, M., Geiser, T., Gjomarkaj, M., Horvath, I., Howarth, P. H., Johnston, S. L., Joos, G., Krug, N., Montuschi, P., Musial, J., Nizankowska-Mogilnicka, E., Olsson, H. K., Papi, A., Rabe, K. F., Sandstrom, T., Shaw, D. E., Siafakas, N. M., Uhlen, M., Riley, J. H., Bates, S., Middelveld, R. J. M., Wheelock, C. E., Chung, K. F., Adcock, I. M., Sterk, P. J., Djukanovic, R., Nilsson, P., Dahlen, S. -E., James, A., Ahmed, H., Balgoma, D., Bansal, A. T., Baribaud, F., Bigler, J., Billing, B., Bisgaard, H., Boedigheimer, M. J., Bonnelykke, K., Brandsma, J., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Chaiboonchoe, A., Checa, T., Compton, C. H., Corfield, J., Cunoosamy, D., D'Amico, A., Emma, R., Erpenbeck, V. J., Erzen, D., Fichtner, K., Fitch, N., Fleming, L. J., Formaggio, E., Frey, U., Gahlemann, M., Goss, V., Guo, Y. -K., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P. -P. W., Higenbottam, T., Hohlfeld, J. M., Holweg, C. T. J., Knox, A. J., Konradsen, J., Lazarinis, N., Lefaudeux, D., Li, T., Loza, M. J., Lutter, R., Manta, A., Masefield, S., Matthews, J. G., Mazein, A., Meiser, A., Miralpeix, M., Mores, N., Murray, C. S., Myles, D., Naz, S., Nordlund, B., Pahus, L., Pandis, I., Pavlidis, S., Postle, A., Powel, P., Rao, N., Reinke, S., Roberts, A., Roberts, G., Rowe, A., Schofield, J. P. R., Seibold, W., Selby, A., Sigmund, R., Singer, F., Sjodin, M., Skipp, P. J., Sousa, A. R., Sun, K., Thornton, B., Uddin, M., van Aalderen, W. M., van Geest, M., Vestbo, J., Vissing, N. H., Wagener, A. H., Wagers, S. S., Weiszhart, Z., Wheelock, A., Wilson, S. J., Yasinska, V., Brusselle, G. G., Campbell, D. A., Contoli, M., Damm, K., de Rudder, I., Delin, I., Devautour, C., Duplaga, M., Eduards, M., Ek, A., Ekstrom, T., Figiel, E., Gaber, F., Gauw, S., Gawlewicz-Mroczka, A., Gerding, D., Haque, S., Hewitt, L., Hiemstra, P. S., Holgate, S. T., Holloway, J., Kania, A., Kanniess, F., Karlsson, O., Kips, J. C., Kumlin, M., Lantz, A. -S., Magnussen, H., Mallia, P., Martling, I., Meziane, L., Oikonomidou, E., Olsson, M., Pace, E., Papadopouli, E., Papadopoulos, N., Plataki, M., Profita, M., Reinius, L. E., Richter, K., Robinson, D. S., Romagnoli, M., Samara, K., Schelfhout, V., Skedinger, M., Stamataki, E., ten Brinke, A., Vachier, I., Wallen-Nielsen, E., van Veen, I., Weersink, E., Zervas, E., and Ziolkowska-Graca, B.

Subjects
Blood Proteins, Humans, Inflammation, Proteomics, Severity of Illness Index, Steroids, Asthma, Quality of Life
Published
2022

6. Circulating inflammatory cytokines predict severity disease in hospitalized COVID-19 patients: A prospective multicenter study of the European DRAGON consortium.

Author

Polese, Barbara, Ernst, Marie, Henket, Monique, Ernst, Benoit, Winandy, Marie, Njock, Makon-Sébastien, Blockx, Céline, Kovacs, Stéphanie, Watar, Florence, Peired, Anna Julie, Tomassetti, Sara, Nardi, Cosimo, Gofflot, Stéphanie, Rahmouni, Souad, Schofield, James PR, Penrice-Randal, Rebekah, Skipp, Paul J., Strazzeri, Fabio, Parkinson, Erika, and Darcis, Gilles

Abstract

COVID-19 has put a huge strain on the healthcare systems worldwide, requiring unprecedented intensive care resources. There is still an unmet clinical need for easily available biomarkers capable of predicting the risk for severe disease. The main goal of this prospective multicenter study was to identify biomarkers that could predict ICU admission and in-hospital mortality. We prospectively recruited COVID-19 PCR positive patients in two hospitals, in Belgium and Italy. Blood samples were collected at hospital admission and 20 potential biomarkers were measured with the Luminex technology. Logistic regression models were performed to identify the biomarkers that, alone or together, were associated with patient disease severity. Our study demonstrates that elevated levels of circulating inflammatory cytokines were associated with disease severity in COVID-19 hospitalized patients. CXCL10, IL-4, IL-6 and MCP-1 values were predictive of ICU admission. Elevated levels of IL-6 and MCP-1 were also associated with in hospital death in COVID-19 hospitalized patients. Altogether, elevated and correlated inflammatory cytokines in the blood of COVID-19 patients at hospital admission are predictive of disease severity and suggest a dysregulated inflammation induced by SARS-CoV-2 infection. • Plasma cytokines are associated with disease severity in COVID-19 patients. • CXCL10, IL-4, IL-6 and MCP-1 blood values are predictive of ICU admission. • IL-6 and MCP-1 plasma levels are associated with in hospital death in COVID-19. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Urinary Leukotriene E4 and Prostaglandin D2 Metabolites Increase in Adult and Childhood Severe Asthma Characterized by Type 2 Inflammation. A Clinical Observational Study

Author

Kolmert, Johan, primary, Gómez, Cristina, additional, Balgoma, David, additional, Sjödin, Marcus, additional, Bood, Johan, additional, Konradsen, Jon R., additional, Ericsson, Magnus, additional, Thörngren, John-Olof, additional, James, Anna, additional, Mikus, Maria, additional, Sousa, Ana R., additional, Riley, John H., additional, Bates, Stewart, additional, Bakke, Per S., additional, Pandis, Ioannis, additional, Caruso, Massimo, additional, Chanez, Pascal, additional, Fowler, Stephen J., additional, Geiser, Thomas, additional, Howarth, Peter, additional, Horváth, Ildikó, additional, Krug, Norbert, additional, Montuschi, Paolo, additional, Sanak, Marek, additional, Behndig, Annelie, additional, Shaw, Dominick E., additional, Knowles, Richard G., additional, Holweg, Cécile T. J., additional, Wheelock, Åsa M., additional, Dahlén, Barbro, additional, Nordlund, Björn, additional, Alving, Kjell, additional, Hedlin, Gunilla, additional, Chung, Kian Fan, additional, Adcock, Ian M., additional, Sterk, Peter J., additional, Djukanovic, Ratko, additional, Dahlén, Sven-Erik, additional, Wheelock, Craig E., additional, Ahmed, H., additional, Auffray, C., additional, Bansal, A. T., additional, Bel, E. H., additional, Bigler, J., additional, Billing, B., additional, Baribaud, F., additional, Bisgaard, H., additional, Boedigheimer, M. J., additional, Bønnelykke, K., additional, Brandsma, J., additional, Brinkman, P., additional, Bucchioni, E., additional, Burg, D., additional, Bush, A., additional, Chaiboonchoe, A., additional, Compton, C. H., additional, Corfield, J., additional, Cunoosamy, D., additional, D’Amico, A., additional, De Meulder, B., additional, Erpenbeck, V. J., additional, Erzen, D., additional, Fichtner, K., additional, Fitch, N., additional, Fleming, L. J., additional, Formaggio, E., additional, Frey, U., additional, Gahlemann, M., additional, Goss, V., additional, Guo, Y., additional, Hashimoto, S., additional, Haughney, J., additional, Hekking, P. W., additional, Higenbottam, T., additional, Hohlfeld, J. M., additional, Knox, A. J., additional, Lazarinis, N., additional, Lefaudeux, D., additional, Loza, M. J., additional, Lutter, R., additional, Manta, A., additional, Masefield, S., additional, Matthews, J. G., additional, Mazein, A., additional, Meiser, A., additional, Middelveld, R. J. M., additional, Miralpeix, M., additional, Mores, N., additional, Murray, C. S., additional, Musial, J., additional, Myles, D., additional, Pahus, L., additional, Pavlidis, S., additional, Postle, A., additional, Powel, P., additional, Praticò, G., additional, PuigValls, M., additional, Rao, N., additional, Roberts, A., additional, Roberts, G., additional, Rowe, A., additional, Sandström, T., additional, Schofield, J. P. R., additional, Seibold, W., additional, Selby, A., additional, Sigmund, R., additional, Singer, F., additional, Skipp, P. J., additional, Smicker, M., additional, Sun, K., additional, Thornton, B., additional, Uddin, M., additional, van Aalderen, W. M., additional, van Geest, M., additional, Vestbo, J., additional, Vissing, N. H., additional, Wagener, A. H., additional, Wagers, S. S., additional, Weiszhart, Z., additional, Wilson, S. J., additional, and Östling, J., additional

Published
2021
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9. Treatable traits in the European U-BIOPRED adult asthma cohorts

Author

Simpson, Andrew J., Hekking, Pieter-Paul, Shaw, Dominick E., Fleming, L. J., Roberts, Graham, Riley, John H., Bates, Stewart, Sousa, A. R., Bansal, A. T., Pandis, Ioannis, Sun, K., Bakke, Per S., Caruso, Massimo, Dahlen, Barbro, Dahlen, Sven-Erik, Horvath, Ildiko, Krug, Norbert, Montuschi, Paolo, Sandstrom, Thomas, Singer, Florian, Adcock, I. M., Wagers, Scott S., Djukanovic, R., Chung, Kian Fan, Sterk, P. J., Fowler, S. J., Ahmed, H., Auffray, C., Bakke, P., Baribaud, F., Bates, S., Bel, E. H., Bigler, J., Bisgaard, H., Boedigheimer, M. J., Bonnelykke, K., Brandsma, J., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Caruso, M., Chaiboonchoe, A., Chanez, P., Chung, F. K., Compton, C. H., Corfield, J., D'Amico, A., Dahlen, B., Dahlen, S. E., De Meulder, B., Erpenbeck, V. J., Erzen, D., Fichtner, K., Fitch, N., Formaggio, E., Frey, U., Gahlemann, M., Geiser, T., Goss, V., Guo, Y., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P. W., Higenbottam, T., Hohlfeld, J. M., Holweg, C., Horvath, I., Howarth, P., James, A. J., Knowles, R., Knox, A. J., Krug, N., Lefaudeux, D., Loza, M. J., Lutter, R., Manta, A., Masefield, S., Matthews, J. G., Mazein, A., Meiser, A., Middelveld, R. J. M., Miralpeix, M., Montuschi, P., Mores, N., Murray, C. S., Musial, J., Myles, D., Pahus, L., Pandis, I., Pavlidis, S., Postle, A., Powel, P., Pratico, G., Puig Valls, M., Rao, N., Riley, J., Roberts, A., Roberts, G., Rowe, A., Sandstrom, T., Schofield, J. P. R., Seibold, W., Selby, A., Shaw, D. E., Sigmund, R., Singer, F., Skipp, P. J., van Aalderen, W. M., van Geest, M., Vestbo, J., Vissing, N. H., Wagener, A. H., Wagers, S. S., Weiszhart, Z., Wheelock, C. E., and Wilson, S. J.

Abstract

mprovements in asthma outcomes have stalled over the past decade, which may be attributed to treating patients on the basis of a generic diagnostic label. The taxonomy “Treatable Traits” was proposed by Agusti et al (2016) as a precision medicine approach for the diagnosis and management of chronic airway diseases that is based on the identification of genetic, phenotypic and psychosocial characteristics for which therapeutic interventions are known to improve respiratory health ...

Published
2019

10. Epithelial dysregulation in obese severe asthmatics with gastro-oesophageal reflux

Author

Perotin, Jeanne-Marie, Schofield, James P. R., Wilson, Susan J., Ward, Jonathan, Brandsma, Joost, Strazzeri, Fabio, Bansal, Aruna, Yang, Xian, Rowe, Anthony, Corfield, Julie, Lutter, Rene, Shaw, Dominick E., Bakke, Per S., Caruso, Massimo, Dahlen, Barbro, Fowler, Stephen J., Horvath, Ildiko, Howarth, Peter, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandstrom, Thomas, Sun, Kai, Pandis, Ioannis, Auffray, Charles, De Meulder, Bertrand, Lefaudeux, Diane, Riley, John H., Sousa, Ana R., Dahlen, Sven-Erik, Adcock, Ian M., Chung, Kian Fan, Sterk, Peter J., Skipp, Paul J., Collins, Jane E., Davies, Donna E., Djukanovic, Ratko, Adcock, I. M., Ahmed, H., Auffray, C., Bakke, P., Banssal, A. T., Baribaud, F., Bates, S., Bel, E. H., Bigler, J., Bisgaard, H., Boedigheimer, M. J., Bonnelykke, K., Brandsma, J., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Caruso, M., Chaiboonchoe, A., Chanez, P., Chung, K. F., Compton, C. H., Corfield, J., D'Amico, A., Dahlen, S. E., De Meulder, B., Djukanovic, R., Erpenbeck, V. J., Erzen, D., Fichtner, K., Fitch, N., Fleming, L. J., Formaggio, E., Fowler, S. J., Frey, U., Gahlemann, M., Geiser, T., Guo, Y., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P. W., Higenbottam, T., Hohlfeld, J. M., Holweg, C., Horvath, I., Howarth, P., James, A. J., Knowles, R., Knox, A. J., Krug, N., Lefaudeux, D., Loza, M. J., Lutter, R., Manta, A., Masefield, S., Matthews, J. G., Mazein, A., Meiser, A., Middelveld, R. J. M., Miralpeix, M., Montuschi, P., Mores, N., Murray, C. S., Musial, J., Myles, D., Pahus, L., Pandis, I., Pavlidis, S., Powell, P., Pratico, G., Puig Valls, M., Rao, N., Riley, J., Roberts, A., Roberts, G., Rowe, A., Sandstrom, T., Seibold, W., Selby, A., Shaw, D. E., Sigmund, R., Singer, F., Skipp, P. J., Sousa, A. R., Sterk, P. J., Sun, K., Thornton, B., van Aalderen, W. M., van Geest, M., Vestbo, J., Vissing, N. H., Wagener, A. H., Wagers, S. S., Weiszhart, Z., Wheelock, C. E., Wilson, S. J., Aliprantis, Antonios, Allen, David, Alving, Kjell, Badorrek, P., Balgoma, David, Ballereau, S., Barber, Clair, Batuwitage, Manohara Kanangana, Bautmans, An, Bedding, A., Behndig, A. F., Beleta, Jorge, Berglind, A., Berton, A., Bochenek, G., Braun, A., Campagna, D., Carayannopoulos, L., Casaulta, C., Chaleckis, Romanas, Dahlen, B., Davison, T., De Alba, J., De Lepeleire, I., Dekker, T., Delin, I., Dennison, P., Dijkhuis, A., Dodson, P., Dyson, K., Edwards, J., El Hadjam, L., Emma, R., Ericsson, M., Faulenbach, C., Flood, Breda, Galffy, G., Gallart, H., Garissi, D., Gent, J., de Verdier, M. Gerhardsson, Gibeon, D., Gomez, Cristina, Gove, K., Guillmant-Farry, E., Henriksson, E., Hewitt, L., Hoda, U., Hu, Richard, Hu, S., Hu, X., Jeyasingham, E., Johnson, K., Jullian, N., Kamphuis, J., Kennington, E. J., Kerry, D., Kerry, G., Klueglich, M., Knobel, H., Kolmert, Johan, Konradsen, J. R., Kots, M., Kretsos, Kosmas, Krueger, L., Kuo, S., Kupczyk, M., Lambrecht, B., Lantz, A-S, Larminie, Christopher, Larsson, L. X., Latzin, P., Lazarinis, N., Lemonnier, N., Lone-Latif, S., Lowe, L. A., Marouzet, L., Martin, J., Mathon, C., McEvoy, L., Meah, S., Menzies-Gow, A., Metcalf, L., Mikus, M., Monk, P., Naz, S., Nething, K., Nicholas, B., Nihlen, U., Nilsson, Peter, Niven, R., Nordlund, B., Nsubuga, S., Ostling, J., Pacino, A., Palkonen, S., Pellet, J., Pennazza, G., Petren, A., Pink, S., Pison, C., Postle, A., Rahman-Amin, M., Ravanetti, L., Ray, E., Reinke, S., Reynolds, L., Riemann, K., Robberechts, Martine, Rocha, J. P., Rossios, C., Russell, K., Rutgers, M., Santini, G., Santoninco, M., Saqi, M., Schoelch, C., Schofield, J. P. R., Scott, S., Sehgal, N., Sjodin, M., Smids, B., Smith, Caroline, Smith, J., Smith, K. M., Soderman, P., Sogbessan, A., Spycher, F., Staykova, D., Stephan, S., Stokholm, J., Strandberg, K., Sunther, M., Szentkereszty, M., Tamasi, L., Tariq, K., Thorngren, J-O, Thorsen, Jonathan, Valente, S., van de Pol, Marianne, van Drunen, C. M., Van Eyll, J., Versnel, J., Vink, A., von Garnier, C., Vyas, A., Wald, F., Walker, S., Ward, J., Wetzel, K., Wiegman, C., Williams, S., Yang, X., Yeyasingham, E., Yu, W., Zetterquist, W., Zolkipli, Z., Zwinderman, A. H., Prins, J-B, Visintin, L., Evans, H., Puhl, M., Buzermaniene, L., Hudson, V., Bond, L., de Boer, P., Widdershoven, G., Supple, D., Hamerlijnck, D., Negus, J., Sergison, L., Onstein, S., MacNee, W., Bernardini, R., Bont, Louis, Wecksell, P-A, Draper, Aleksandra, Gozzard, Neil, Perotin, Jeanne-Marie, Schofield, James P. R., Wilson, Susan J., Ward, Jonathan, Brandsma, Joost, Strazzeri, Fabio, Bansal, Aruna, Yang, Xian, Rowe, Anthony, Corfield, Julie, Lutter, Rene, Shaw, Dominick E., Bakke, Per S., Caruso, Massimo, Dahlen, Barbro, Fowler, Stephen J., Horvath, Ildiko, Howarth, Peter, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandstrom, Thomas, Sun, Kai, Pandis, Ioannis, Auffray, Charles, De Meulder, Bertrand, Lefaudeux, Diane, Riley, John H., Sousa, Ana R., Dahlen, Sven-Erik, Adcock, Ian M., Chung, Kian Fan, Sterk, Peter J., Skipp, Paul J., Collins, Jane E., Davies, Donna E., Djukanovic, Ratko, Adcock, I. M., Ahmed, H., Auffray, C., Bakke, P., Banssal, A. T., Baribaud, F., Bates, S., Bel, E. H., Bigler, J., Bisgaard, H., Boedigheimer, M. J., Bonnelykke, K., Brandsma, J., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Caruso, M., Chaiboonchoe, A., Chanez, P., Chung, K. F., Compton, C. H., Corfield, J., D'Amico, A., Dahlen, S. E., De Meulder, B., Djukanovic, R., Erpenbeck, V. J., Erzen, D., Fichtner, K., Fitch, N., Fleming, L. J., Formaggio, E., Fowler, S. J., Frey, U., Gahlemann, M., Geiser, T., Guo, Y., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P. W., Higenbottam, T., Hohlfeld, J. M., Holweg, C., Horvath, I., Howarth, P., James, A. J., Knowles, R., Knox, A. J., Krug, N., Lefaudeux, D., Loza, M. J., Lutter, R., Manta, A., Masefield, S., Matthews, J. G., Mazein, A., Meiser, A., Middelveld, R. J. M., Miralpeix, M., Montuschi, P., Mores, N., Murray, C. S., Musial, J., Myles, D., Pahus, L., Pandis, I., Pavlidis, S., Powell, P., Pratico, G., Puig Valls, M., Rao, N., Riley, J., Roberts, A., Roberts, G., Rowe, A., Sandstrom, T., Seibold, W., Selby, A., Shaw, D. E., Sigmund, R., Singer, F., Skipp, P. J., Sousa, A. R., Sterk, P. J., Sun, K., Thornton, B., van Aalderen, W. M., van Geest, M., Vestbo, J., Vissing, N. H., Wagener, A. H., Wagers, S. S., Weiszhart, Z., Wheelock, C. E., Wilson, S. J., Aliprantis, Antonios, Allen, David, Alving, Kjell, Badorrek, P., Balgoma, David, Ballereau, S., Barber, Clair, Batuwitage, Manohara Kanangana, Bautmans, An, Bedding, A., Behndig, A. F., Beleta, Jorge, Berglind, A., Berton, A., Bochenek, G., Braun, A., Campagna, D., Carayannopoulos, L., Casaulta, C., Chaleckis, Romanas, Dahlen, B., Davison, T., De Alba, J., De Lepeleire, I., Dekker, T., Delin, I., Dennison, P., Dijkhuis, A., Dodson, P., Dyson, K., Edwards, J., El Hadjam, L., Emma, R., Ericsson, M., Faulenbach, C., Flood, Breda, Galffy, G., Gallart, H., Garissi, D., Gent, J., de Verdier, M. Gerhardsson, Gibeon, D., Gomez, Cristina, Gove, K., Guillmant-Farry, E., Henriksson, E., Hewitt, L., Hoda, U., Hu, Richard, Hu, S., Hu, X., Jeyasingham, E., Johnson, K., Jullian, N., Kamphuis, J., Kennington, E. J., Kerry, D., Kerry, G., Klueglich, M., Knobel, H., Kolmert, Johan, Konradsen, J. R., Kots, M., Kretsos, Kosmas, Krueger, L., Kuo, S., Kupczyk, M., Lambrecht, B., Lantz, A-S, Larminie, Christopher, Larsson, L. X., Latzin, P., Lazarinis, N., Lemonnier, N., Lone-Latif, S., Lowe, L. A., Marouzet, L., Martin, J., Mathon, C., McEvoy, L., Meah, S., Menzies-Gow, A., Metcalf, L., Mikus, M., Monk, P., Naz, S., Nething, K., Nicholas, B., Nihlen, U., Nilsson, Peter, Niven, R., Nordlund, B., Nsubuga, S., Ostling, J., Pacino, A., Palkonen, S., Pellet, J., Pennazza, G., Petren, A., Pink, S., Pison, C., Postle, A., Rahman-Amin, M., Ravanetti, L., Ray, E., Reinke, S., Reynolds, L., Riemann, K., Robberechts, Martine, Rocha, J. P., Rossios, C., Russell, K., Rutgers, M., Santini, G., Santoninco, M., Saqi, M., Schoelch, C., Schofield, J. P. R., Scott, S., Sehgal, N., Sjodin, M., Smids, B., Smith, Caroline, Smith, J., Smith, K. M., Soderman, P., Sogbessan, A., Spycher, F., Staykova, D., Stephan, S., Stokholm, J., Strandberg, K., Sunther, M., Szentkereszty, M., Tamasi, L., Tariq, K., Thorngren, J-O, Thorsen, Jonathan, Valente, S., van de Pol, Marianne, van Drunen, C. M., Van Eyll, J., Versnel, J., Vink, A., von Garnier, C., Vyas, A., Wald, F., Walker, S., Ward, J., Wetzel, K., Wiegman, C., Williams, S., Yang, X., Yeyasingham, E., Yu, W., Zetterquist, W., Zolkipli, Z., Zwinderman, A. H., Prins, J-B, Visintin, L., Evans, H., Puhl, M., Buzermaniene, L., Hudson, V., Bond, L., de Boer, P., Widdershoven, G., Supple, D., Hamerlijnck, D., Negus, J., Sergison, L., Onstein, S., MacNee, W., Bernardini, R., Bont, Louis, Wecksell, P-A, Draper, Aleksandra, and Gozzard, Neil

Published
2019
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11. IL-17-high asthma with features of a psoriasis immunophenotype

Author

Östling, Jörgen, van Geest, Marleen, Schofield, James P. R., Jevnikar, Zala, Wilson, Susan, Ward, Jonathan, Lutter, Rene, Shaw, Dominick E., Bakke, Per S., Caruso, Massimo, Dahlen, Sven-Erik, Fowler, Stephen J., Horvath, Ildiko, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandström, Thomas, Sun, Kai, Pandis, Ioannis, Auffray, Charles, Sousa, Ana R., Guo, Yike, Adcock, Ian M., Howarth, Peter, Chung, Kian Fan, Bigler, Jeanette, Sterk, Peter J., Skipp, Paul J., Djukanovic, Ratko, Vaarala, Outi, Ahmed, H., Auffray, C., Bakke, P., Bansal, A. T., Baribaud, F., Bates, S., Bel, E. H., Bigler, J., Bisgaard, H., Boedigheimer, M. J., Bonnelykke, K., Brandsma, J., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Caruso, M., Chaiboonchoe, A., Chanez, P., Chung, K. F., Compton, C. H., Corfield, J., D'Amico, A., Dahlen, S. E., De Meulder, B., Djukanovic, R., Erpenbeck, V. J., Erzen, D., Fichtner, K., Fitch, N., Fleming, L. J., Formaggio, E., Fowler, S. J., Frey, U., Gahlemann, M., Geiser, T., Guo, Y., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P. W., Higenbottam, T., Hohlfeld, J. M., Holweg, C., Horvath, I., Howarth, P., James, A. J., Knowles, R., Knox, A. J., Krug, N., Lefaudeux, D., Loza, M. J., Lutter, R., Manta, A., Masefield, S., Matthews, J. G., Mazein, A., Meiser, A., Middelveld, R. J. M., Miralpeix, M., Montuschi, P., Mores, N., Murray, C. S., Musial, J., Myles, D., Pahus, L., Pandis, I., Pavlidis, S., Powell, P., Pratico, G., Valls, M. Puig, Rao, N., Riley, J., Roberts, A., Roberts, G., Rowe, A., Sandström, T., Seibold, W., Selby, A., Shaw, D. E., Sigmund, R., Singer, F., Skipp, P. J., Sousa, A. R., Sterk, P. J., Sun, K., Thornton, B., van Aalderen, W. M., van Geest, M., Vestbo, J., Vissing, N. H., Wagener, A. H., Wagers, S. S., Weiszhart, Z., Wheelock, C. E., Wilson, S. J., Östling, Jörgen, van Geest, Marleen, Schofield, James P. R., Jevnikar, Zala, Wilson, Susan, Ward, Jonathan, Lutter, Rene, Shaw, Dominick E., Bakke, Per S., Caruso, Massimo, Dahlen, Sven-Erik, Fowler, Stephen J., Horvath, Ildiko, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandström, Thomas, Sun, Kai, Pandis, Ioannis, Auffray, Charles, Sousa, Ana R., Guo, Yike, Adcock, Ian M., Howarth, Peter, Chung, Kian Fan, Bigler, Jeanette, Sterk, Peter J., Skipp, Paul J., Djukanovic, Ratko, Vaarala, Outi, Ahmed, H., Auffray, C., Bakke, P., Bansal, A. T., Baribaud, F., Bates, S., Bel, E. H., Bigler, J., Bisgaard, H., Boedigheimer, M. J., Bonnelykke, K., Brandsma, J., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Caruso, M., Chaiboonchoe, A., Chanez, P., Chung, K. F., Compton, C. H., Corfield, J., D'Amico, A., Dahlen, S. E., De Meulder, B., Djukanovic, R., Erpenbeck, V. J., Erzen, D., Fichtner, K., Fitch, N., Fleming, L. J., Formaggio, E., Fowler, S. J., Frey, U., Gahlemann, M., Geiser, T., Guo, Y., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P. W., Higenbottam, T., Hohlfeld, J. M., Holweg, C., Horvath, I., Howarth, P., James, A. J., Knowles, R., Knox, A. J., Krug, N., Lefaudeux, D., Loza, M. J., Lutter, R., Manta, A., Masefield, S., Matthews, J. G., Mazein, A., Meiser, A., Middelveld, R. J. M., Miralpeix, M., Montuschi, P., Mores, N., Murray, C. S., Musial, J., Myles, D., Pahus, L., Pandis, I., Pavlidis, S., Powell, P., Pratico, G., Valls, M. Puig, Rao, N., Riley, J., Roberts, A., Roberts, G., Rowe, A., Sandström, T., Seibold, W., Selby, A., Shaw, D. E., Sigmund, R., Singer, F., Skipp, P. J., Sousa, A. R., Sterk, P. J., Sun, K., Thornton, B., van Aalderen, W. M., van Geest, M., Vestbo, J., Vissing, N. H., Wagener, A. H., Wagers, S. S., Weiszhart, Z., Wheelock, C. E., and Wilson, S. J.

Abstract

Background: The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required. Objective: We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity. Methods: Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17–high and IL-13–high asthma phenotypes. Results: Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17–high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and β-defensin. Conclusion: The IL-17–high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.

Published
2019
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12. Sputum proteomic signature of gastro-oesophageal reflux in patients with severe asthma

Author

Tariq, K., Schofield, J. P. R., Nicholas, B. L., Burg, D., Brandsma, J., Bansal, A. T., Wilson, S. J., Lutter, R., Fowler, S. J., Bakke, ., Caruso, M., Dahlen, B., Horvath, I., Krug, N., Montuschi, P., Sanak, M., Sandström, Thomas, Geiser, T., Pandis, I., Sousa, A. R., Adcock, I. M., Shaw, D. E., Auffray, C., Howarth, P. H., Sterk, P. J., Chung, K. F., Skipp, P. J., Dimitrov, B., Djukanovic, R., Tariq, K., Schofield, J. P. R., Nicholas, B. L., Burg, D., Brandsma, J., Bansal, A. T., Wilson, S. J., Lutter, R., Fowler, S. J., Bakke, ., Caruso, M., Dahlen, B., Horvath, I., Krug, N., Montuschi, P., Sanak, M., Sandström, Thomas, Geiser, T., Pandis, I., Sousa, A. R., Adcock, I. M., Shaw, D. E., Auffray, C., Howarth, P. H., Sterk, P. J., Chung, K. F., Skipp, P. J., Dimitrov, B., and Djukanovic, R.

Abstract

Gastro-oesophageal reflux disease (GORD) has long been associated with poor asthma control without an established cause-effect relationship. 610 asthmatics (421 severe/88 mild-moderate) and 101 healthy controls were assessed clinically and a subset of 154 severe asthmatics underwent proteomic analysis of induced sputum using untargeted mass spectrometry, LC-IMS-MSE. Univariate and multiple logistic regression analyses (MLR) were conducted to identify proteins associated with GORD in this cohort. When compared to mild/moderate asthmatics and healthy individuals, respectively, GORD was three-and ten-fold more prevalent in severe asthmatics and was associated with increased asthma symptoms and oral corticosteroid use, poorer quality of life, depression/anxiety, obesity and symptoms of sino-nasal disease. Comparison of sputum proteomes in severe asthmatics with and without active GORD showed five differentially abundant proteins with described roles in antimicrobial defences, systemic inflammation and epithelial integrity. Three of these were associated with active GORD by multiple linear regression analysis: Ig lambda variable 1-47 (p = 0.017) and plasma protease C1 inhibitor (p = 0.043), both in lower concentrations, and lipocalin-1 (p = 0.034) in higher concentrations in active GORD. This study provides evidence which suggests that reflux can cause subtle perturbation of proteins detectable in the airways lining fluid and that severe asthmatics with GORD may represent a distinct phenotype of asthma.

Published
2019
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13. A computational framework for complex disease stratification from multiple large-scale datasets

Author

De Meulder, B., Lefaudeux, D., Bansal, A. T., Mazein, A., Chaiboonchoe, A., Ahmed, H., Balaur, I., Saqi, M., Pellet, J., Ballereau, S., Lemonnier, N., Sun, K., Pandis, I., Yang, X., Batuwitage, M., Kretsos, K., van Eyll, J., Bedding, A., Davison, T., Dodson, P., Larminie, C., Postle, A., Corfield, J., Djukanovic, R., Chung, K. F., Adcock, I. M., Guo, Y. -K., Sterk, P. J., Manta, A., Rowe, A., Baribaud, F., Auffray, C., Gibeon, D., Hoda, U., Kuo, S., Meah, S., Meiser, A., Fleming, L. J., Hu, S., Pavlidis, S., Rossios, C., Russel, K., Wiegman, C., Nezhad, A. T., Oehmichen, A., O'Malley, D., Guitton, F., Emam, I., Agapow, P., Rice, P., Miles, S., Elyasigomari, V., Bel, E., Brinkman, P., Dekker, T., Dijkhuis, A., Hashimoto, S., Hekking, P. -P., Lone-Latif, S., Lutter, R., Ravanetti, L., Smids, B., van Aalderen, W., van de Pol, M., van Drunen, K., van Drunen, M., Wagener, A., Zwinderman, K., Adriaens, N., Carusi, A. M., Richard, F., Nogueira, M. M., Taibi, N., Brasier, O., Aliprantis, A., Alving, K., Faulenbach, C., Braun, A., Hohlfeld, J., Krug, N., Badorrek, P., Bakke, P., Berglind, A., Chaleckis, R., Dahlen, B., Delin, I., Gallart, H., Gomez, C., Hedlin, G., Henriksson, E., James, A. J., Kolmert, J., Konradsen, J., Kupczyk, M., Lantz, A. -S., Lazarinis, L., Mathon, C., Middelveld, R., Naz, S., Nordlund, B., Petren, A., Reinke, S., Sjodin, M., Soderman, P., Strandberg, K., Wheelock, C. E., Zetterquist, W., Balgoma, D., Brandsma, J., Burg, D., Dennison, P., Nicholas, B., Schofield, J. P. R., Skipp, P. J., Staykova, D., Tariq, K., Ward, J., Wilson, S. J., Barber, C., Loza, M. J., Bautmans, A., Sandstrom, T., Behndig, A. F., De Alba, J., Beleta, J., Berton, A., de Verdier, M. G., Nihlen, U., Ostling, J., Dalentoft, T., Lindgren, E., Boedigheimer, M. J., Hu, R., Hu, X., Yu, W., Bigler, J., Bonnelykke, K., Thorsen, J., Vising, N., Bisgaard, H., Bochenek, G., Caruso, M., Emma, R., Campagna, D., Thornton, B., Carayannopoulos, L., Gent, J., Manzies-Gow, A., Sogbesan, A., da Purificacao Rocha, P. C., Pedro, J., Chanez, P., Edwards, J., Flood, B., Hudson, V., Kennington, E. J., Metcalf, L., Rahman-Amin, M., Reynolds, L., Roberts, A., Smith, J., Supple, D., Versnel, J., Walker, S., Coleman, C., Hasan, S., Compton, C., Myles, D., Riley, J., Sousa, A. R., Yeyasingham, E., Pennazza, G., Santoninco, M., D'Amico, A., Dahlen, S. -E., de Boer, P., Robberechts, M., De Lepeleire, I., Fitch, N., Garret, T., Wagers, S., Draper, A., Thorngren, J. -O., Ericsson, M., Erpenbeck, V., Kluglich, M., Nething, K., Riemann, K., Schoelch, C., Seibold, W., Sigmund, R., Wald, F., Wetzel, K., Fichtner, K., Erzen, D., Galffy, G., Horvath, I., Szentkereszty, M., Tamasi, L., Fowler, S. J., Krueger, L., Singer, F., Frey, U., Gahlemann, M., Geiser, T., Hewitt, L., Howarth, P., Marouzet, L., Martin, J., Pink, S., Ray, E., Roberts, G., Smith, C., Gove, K., Gozzard, N., Williams, S., Haughney, J., Higgenbottam, T., Matthews, J. G., Holweg, C., Rutgers, M., Kamphuis, J., Kerry, D., Vink, A., Knobel, H., Knowles, R., Shaw, D. E., Smith, K. M., Know, A., Kots, M., Lambrecht, B., Masefield, S., Nilsson, P., Mikus, M., Miralpeix, M., Monk, P., Mores, N., Valente, S., Montuschi, P., Murray, C. S., Musial, J., Pacino, A., Pahus, L., Palkonen, S., Powel, P., Rao, N., Santini, G., Vestbo, J., von Garnier, C., Weiszhart, Z., Woodcock, A., Biryukov, M., Schneider, R., Herzinger, S., Satagopam, V., Gu, W., da Silva, A. B., Tielmann, A., Bergeron, J., Gaudette, A., Silberberg, A., Henderson, D., Hayat, S., Elefsinioti, A., Moltzen, E. K., Harbo, I. S., Birgitte, J., Bratfalean, D., Houston, P., Kisler, B., Capdevila, F. B., Verbeeck, D., Marchetti, G., Rahal, G., Schuermann, H. D., Mazuranok, L., Hendlich, M., Painell'S, L., Marren, D., Martasek, J., Rimell, J., Romacker, M., Braxenthaler, M., Sansone, S. -A., Rocca-Serra, P., Commission of the European Communities, Pulmonology, Graduate School, Experimental Immunology, Paediatric Pulmonology, Ear, Nose and Throat, Epidemiology and Data Science, APH - Methodology, ARD - Amsterdam Reproduction and Development, Consortium, U-Biopred Study Group And The Etriks, Rocca-Serra, P, Sansone, S, De Meulder, Bertrand [0000-0002-2108-7657], and Apollo - University of Cambridge Repository

Subjects
Quality Control, 0301 basic medicine, Computer science, Bioinformatics, Systems biology, Big data, Environmental data, Machine Learning, Set (abstract data type), 03 medical and health sciences, Structural Biology, Modelling and Simulation, Cluster Analysis, U-BIOPRED Study Group and the eTRIKS Consortium, Disease, False Positive Reactions, Cluster analysis, Molecular signatures, Molecular Biology, lcsh:QH301-705.5, ‘Omics data, 'Omics data, business.industry, Systems Biology, Applied Mathematics, 1199 Other Medical And Health Sciences, Data science, 3. Good health, Computer Science Applications, Systems medicine, 030104 developmental biology, lcsh:Biology (General), Feature (computer vision), Modeling and Simulation, Stratification, Scale (map), business, Biomarkers, Research Article
Abstract

Background Multilevel data integration is becoming a major area of research in systems biology. Within this area, multi-‘omics datasets on complex diseases are becoming more readily available and there is a need to set standards and good practices for integrated analysis of biological, clinical and environmental data. We present a framework to plan and generate single and multi-‘omics signatures of disease states. Methods The framework is divided into four major steps: dataset subsetting, feature filtering, ‘omics-based clustering and biomarker identification. Results We illustrate the usefulness of this framework by identifying potential patient clusters based on integrated multi-‘omics signatures in a publicly available ovarian cystadenocarcinoma dataset. The analysis generated a higher number of stable and clinically relevant clusters than previously reported, and enabled the generation of predictive models of patient outcomes. Conclusions This framework will help health researchers plan and perform multi-‘omics big data analyses to generate hypotheses and make sense of their rich, diverse and ever growing datasets, to enable implementation of translational P4 medicine. Electronic supplementary material The online version of this article (10.1186/s12918-018-0556-z) contains supplementary material, which is available to authorized users.

Published
2018
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14. Lipid phenotyping of lung epithelial lining fluid in healthy human volunteers

Author

Brandsma, J., Goss, V., Yang, X., Bakke, P. S., Caruso, M., Chanez, P., Dahlen, S. -E., Fowler, S. J., Horvath, I., Krug, N., Montuschi, P., Sanak, M., Sandstrom, T., Shaw, D. E., Chung, K. F., Singer, F., Fleming, L. J., Sousa, A. R., Pandis, I., Bansal, A. T., Sterk, P. J., Djukanovic, R., Postle, A. D., Adcock, I. M., Ahmed, H., Auffray, C., Baribaud, F., Bates, S., Bel, E. H., Bigler, J., Bisgaard, H., Boedigheimer, M. J., Bonnelykke, K., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Chaiboonchoe, A., Chung, F. K., Compton, C. H., Corfield, J., D'Amico, A., Dahlen, B., De Meulder, B., Erpenbeck, V. J., Erzen, D., Fichtner, K., Fitch, N., Formaggio, E., Frey, U., Gahlemann, M., Geiser, T., Guo, Y., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P. W., Higenbottam, T., Hohlfeld, J. M., Holweg, C., Howarth, P., James, A. J., Knowles, R. G., Knox, A. J., Lefaudeux, D., Loza, M. J., Lutter, R., Manta, A., Masefield, S., Matthews, J. G., Mazein, A., Meiser, A., Middelveld, R. J. M., Miralpeix, M., Mores, N., Murray, C. S., Musial, J., Myles, D., Pahus, L., Pavlidis, S., Powel, P., Pratico, G., Puig Valls, M., Rao, N., Riley, J., Roberts, A., Roberts, G., Rowe, A., Schofield, J. P. R., Seibold, W., Selby, A., Sigmund, R., Skipp, P. J., Sun, K., Thornton, B., van Aalderen, W. M., van Geest, M., Vestbo, J., Vissing, N. H., Wagener, A. H., Wagers, S. S., Weiszhart, Z., Wheelock, C. E., Wilson, S. J., Pulmonology, AII - Inflammatory diseases, Commission of the European Communities, and Publica

Subjects
0301 basic medicine, Male, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Epithelial lining fluid, Biochemistry, DISEASE, Analytical Chemistry, Cohort Studies, 0302 clinical medicine, Fibrosis, FIBROSIS, Induced sputum, Lung, COPD, Biochemistry and Molecular Biology, respiratory system, Middle Aged, Lipids, Healthy Volunteers, Cell biology, medicine.anatomical_structure, Phenotype, OBESITY, Original Article, lipids (amino acids, peptides, and proteins), Female, medicine.symptom, Life Sciences & Biomedicine, 0301 Analytical Chemistry, Bronchoalveolar Lavage Fluid, Sputum/chemistry, EXPRESSION, Adult, Settore BIO/14 - FARMACOLOGIA, DYNAMIC LIPIDOMICS, Adolescent, SPUTUM CELL COUNTS, BIOMARKERS, Biology, chronic obstructive pulmonary disease, Bronchoalveolar Lavage Fluid/chemistry, Endocrinology & Metabolism, 03 medical and health sciences, Young Adult, Lipids/analysis, Lung/cytology, Lipidomics, medicine, Humans, SURFACTANT LIPIDS, Aged, Science & Technology, pulmonary fibrosis, Mass spectrometry, Sputum, 0601 Biochemistry And Cell Biology, 1103 Clinical Sciences, Lipid metabolism, Pulmonary surfactant, medicine.disease, Molecular medicine, respiratory tract diseases, Weight status, 030104 developmental biology, 030228 respiratory system, ASTHMA, Biokemi och molekylärbiologi, Homeostasis
Abstract

Background Lung epithelial lining fluid (ELF)—sampled through sputum induction—is a medium rich in cells, proteins and lipids. However, despite its key role in maintaining lung function, homeostasis and defences, the composition and biology of ELF, especially in respect of lipids, remain incompletely understood. Objectives To characterise the induced sputum lipidome of healthy adult individuals, and to examine associations between different ELF lipid phenotypes and the demographic characteristics within the study cohort. Methods Induced sputum samples were obtained from 41 healthy non-smoking adults, and their lipid compositions analysed using a combination of untargeted shotgun and liquid chromatography mass spectrometry methods. Topological data analysis (TDA) was used to group subjects with comparable sputum lipidomes in order to identify distinct ELF phenotypes. Results The induced sputum lipidome was diverse, comprising a range of different molecular classes, including at least 75 glycerophospholipids, 13 sphingolipids, 5 sterol lipids and 12 neutral glycerolipids. TDA identified two distinct phenotypes differentiated by a higher total lipid content and specific enrichments of diacyl-glycerophosphocholines, -inositols and -glycerols in one group, with enrichments of sterols, glycolipids and sphingolipids in the other. Subjects presenting the lipid-rich ELF phenotype also had significantly higher BMI, but did not differ in respect of other demographic characteristics such as age or gender. Conclusions We provide the first evidence that the ELF lipidome varies significantly between healthy individuals and propose that such differences are related to weight status, highlighting the potential impact of (over)nutrition on lung lipid metabolism. Electronic supplementary material The online version of this article (10.1007/s11306-018-1412-2) contains supplementary material, which is available to authorized users.

Published
2018
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15. A novel ACE2isoform is expressed in human respiratory epithelia and is upregulated in response to interferons and RNA respiratory virus infection

Author

Blume, Cornelia, Jackson, Claire L., Spalluto, Cosma Mirella, Legebeke, Jelmer, Nazlamova, Liliya, Conforti, Franco, Perotin, Jeanne-Marie, Frank, Martin, Butler, John, Crispin, Max, Coles, Janice, Thompson, James, Ridley, Robert A., Dean, Lareb S. N., Loxham, Matthew, Reikine, Stephanie, Azim, Adnan, Tariq, Kamran, Johnston, David A., Skipp, Paul J., Djukanovic, Ratko, Baralle, Diana, McCormick, Christopher J., Davies, Donna E., Lucas, Jane S., Wheway, Gabrielle, and Mennella, Vito

Abstract

Angiotensin-converting enzyme 2 (ACE2) is the main entry point in airway epithelial cells for SARS-CoV-2. ACE2 binding to the SARS-CoV-2 protein spike triggers viral fusion with the cell plasma membrane, resulting in viral RNA genome delivery into the host. Despite ACE2’s critical role in SARS-CoV-2 infection, full understanding of ACE2 expression, including in response to viral infection, remains unclear. ACE2was thought to encode five transcripts and one protein of 805 amino acids. In the present study, we identify a novel short isoform of ACE2expressed in the airway epithelium, the main site of SARS-CoV-2 infection. Short ACE2is substantially upregulated in response to interferon stimulation and rhinovirus infection, but not SARS-CoV-2 infection. This short isoform lacks SARS-CoV-2 spike high-affinity binding sites and, altogether, our data are consistent with a model where short ACE2is unlikely to directly contribute to host susceptibility to SARS-CoV-2 infection.

Published
2021
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16. Deep proteomic analysis of Dnmt1 mutant/hypomorphic colorectal cancer cells reveals dysregulation of epithelial–mesenchymal transition and subcellular re-localization of Beta-Catenin

Author

Bowler, Emily H, Smith-Vidal, Alex, Lester, Alex, Bell, Joseph, Wang, Zhenghe, Bell, Christopher G., Wang, Yihua, Divecha, Nullin, Skipp, Paul J., and Ewing, Rob M.

Abstract

ABSTRACTDNA methyltransferase I plays the central role in maintenance of CpG DNA methylation patterns across the genome and alteration of CpG methylation patterns is a frequent and significant occurrence across many cancers. Cancer cells carrying hypomorphic alleles of Dnmt1 have become important tools for understanding Dnmt1 function and CpG methylation. In this study, we analyse colorectal cancer cells with a homozygous deletion of exons 3 to 5 of Dnmt1, resulting in reduced Dnmt1 activity. Although this cell model has been widely used to study the epigenome, the effects of the Dnmt1 hypomorph on cell signalling pathways and the wider proteome are largely unknown. In this study, we perform the first quantitative proteomic analysis of this important cell model and identify multiple signalling pathways and processes that are significantly dysregulated in the hypomorph cells. In Dnmt1 hypomorph cells, we observed a clear and unexpected signature of increased Epithelial-to-Mesenchymal transition (EMT) markers as well as reduced expression and sub-cellular re-localization of Beta-Catenin. Expression of wild-type Dnmt1 in hypomorph cells or knock-down of wild-type Dnmt1 did not recapitulate or rescue the observed protein profiles in Dnmt1 hypomorph cells suggesting that hypomorphic Dnmt1 causes changes not solely attributable to Dnmt1 protein levels. In summary, we present the first comprehensive proteomic analysis of the widely studied Dnmt1 hypomorph colorectal cancer cells and identify redistribution of Dnmt1 and its interaction partner Beta-Catenin.

Published
2020
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17. Large-Scale Label-Free Quantitative Mapping of the Sputum Proteome

Author

Burg, Dominic, Schofield, James P. R., Brandsma, Joost, Staykova, Doroteya, Folisi, Caterina, Bansal, Aruna, Nicholas, Ben, Xian, Yang, Rowe, Anthony, Corfield, Julie, Wilson, Susan, Ward, Jonathan, Lutter, Rene, Fleming, Louise, Shaw, Dominick E., Bakke, Per S., Caruso, Massimo, Dahlen, Sven-Erik, Fowler, Stephen J., Hashimoto, Simone, Horváth, Ildikó, Howarth, Peter, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandström, Thomas, Singer, Florian, Sun, Kai, Pandis, Ioannis, Auffray, Charles, Sousa, Ana R., Adcock, Ian M., Chung, Kian Fan, Sterk, Peter J., Djukanović, Ratko, Skipp, Paul J., and Group, the U-BIOPRED Study

Abstract

Analysis of induced sputum supernatant is a minimally invasive approach to study the epithelial lining fluid and, thereby, provide insight into normal lung biology and the pathobiology of lung diseases. We present here a novel proteomics approach to sputum analysis developed within the U-BIOPRED (unbiased biomarkers predictive of respiratory disease outcomes) international project. We present practical and analytical techniques to optimize the detection of robust biomarkers in proteomic studies. The normal sputum proteome was derived using data-independent HDMSEapplied to 40 healthy nonsmoking participants, which provides an essential baseline from which to compare modulation of protein expression in respiratory diseases. The “core” sputum proteome (proteins detected in ≥40% of participants) was composed of 284 proteins, and the extended proteome (proteins detected in ≥3 participants) contained 1666 proteins. Quality control procedures were developed to optimize the accuracy and consistency of measurement of sputum proteins and analyze the distribution of sputum proteins in the healthy population. The analysis showed that quantitation of proteins by HDMSEis influenced by several factors, with some proteins being measured in all participants’ samples and with low measurement variance between samples from the same patient. The measurement of some proteins is highly variable between repeat analyses, susceptible to sample processing effects, or difficult to accurately quantify by mass spectrometry. Other proteins show high interindividual variance. We also highlight that the sputum proteome of healthy individuals is related to sputum neutrophil levels, but not gender or allergic sensitization. We illustrate the importance of design and interpretation of disease biomarker studies considering such protein population and technical measurement variance.

Published
2018
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18. Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation

Author

Jevnikar, Z., Ostling, J., Ax, E., Calven, J., Thorn, K., Israelsson, E., Oberg, L., Singhania, A., Lau, L. C. K., Wilson, S. J., Ward, J. A., Chauhan, A., Sousa, A. R., De Meulder, B., Loza, M. J., Baribaud, F., Sterk, P. J., Chung, K. F., Sun, K., Guo, Y., Adcock, I. M., Payne, D., Dahlen, B., Chanez, P., Shaw, D. E., Krug, N., Hohlfeld, J. M., Sandstrom, T., Djukanovic, R., James, A., Hinks, T. S. C., Howarth, P. H., Vaarala, O., van Geest, M., Olsson, H., Ahmed, H., Auffray, C., Bakke, P., Bansal, A. T., Bates, S., Bel, E. H., Bigler, J., Bisgaard, H., Boedigheimer, M. J., Bonnelykke, K., Brandsma, J., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Caruso, M., Chaiboonchoe, A., Chung, F. K., Compton, C. H., Corfield, J., D'Amico, Adele, Dahlen, S. E., Erpenbeck, V. J., Erzen, D., Fichtner, K., Fitch, N., Fleming, L. J., Formaggio, E., Fowler, S. J., Frey, U., Gahlemann, M., Geiser, T., Goss, V., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P. W., Higenbottam, T., Holweg, C., Horvath, I., James, A. J., Knowles, R., Knox, A. J., Lefaudeux, D., Manta, A., Matthews, J. G., Mazein, A., Meiser, A., Middelveld, R. J. M., Miralpeix, M., Montuschi, Paolo, Mores, Nadia, Murray, C. S., Musial, J., Myles, D., Pahus, L., Pandis, I., Pavlidis, S., Postle, A., Powel, P., Pratico, G., Rao, N., Riley, J., Roberts, A., Roberts, G., Rowe, A., Schofield, J. P. R., Seibold, W., Selby, A., Sigmund, R., Singer, F., Skipp, P. J., Thornton, B., van Aalderen, W. M., Vestbo, J., Vissing, N. H., Wagener, A. H., Wagers, S. S., Weiszhart, Z., Wheelock, C. E., D'Amico A., Montuschi P. (ORCID:0000-0001-5589-1750), Mores N. (ORCID:0000-0002-4197-0914), Jevnikar, Z., Ostling, J., Ax, E., Calven, J., Thorn, K., Israelsson, E., Oberg, L., Singhania, A., Lau, L. C. K., Wilson, S. J., Ward, J. A., Chauhan, A., Sousa, A. R., De Meulder, B., Loza, M. J., Baribaud, F., Sterk, P. J., Chung, K. F., Sun, K., Guo, Y., Adcock, I. M., Payne, D., Dahlen, B., Chanez, P., Shaw, D. E., Krug, N., Hohlfeld, J. M., Sandstrom, T., Djukanovic, R., James, A., Hinks, T. S. C., Howarth, P. H., Vaarala, O., van Geest, M., Olsson, H., Ahmed, H., Auffray, C., Bakke, P., Bansal, A. T., Bates, S., Bel, E. H., Bigler, J., Bisgaard, H., Boedigheimer, M. J., Bonnelykke, K., Brandsma, J., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Caruso, M., Chaiboonchoe, A., Chung, F. K., Compton, C. H., Corfield, J., D'Amico, Adele, Dahlen, S. E., Erpenbeck, V. J., Erzen, D., Fichtner, K., Fitch, N., Fleming, L. J., Formaggio, E., Fowler, S. J., Frey, U., Gahlemann, M., Geiser, T., Goss, V., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P. W., Higenbottam, T., Holweg, C., Horvath, I., James, A. J., Knowles, R., Knox, A. J., Lefaudeux, D., Manta, A., Matthews, J. G., Mazein, A., Meiser, A., Middelveld, R. J. M., Miralpeix, M., Montuschi, Paolo, Mores, Nadia, Murray, C. S., Musial, J., Myles, D., Pahus, L., Pandis, I., Pavlidis, S., Postle, A., Powel, P., Pratico, G., Rao, N., Riley, J., Roberts, A., Roberts, G., Rowe, A., Schofield, J. P. R., Seibold, W., Selby, A., Sigmund, R., Singer, F., Skipp, P. J., Thornton, B., van Aalderen, W. M., Vestbo, J., Vissing, N. H., Wagener, A. H., Wagers, S. S., Weiszhart, Z., Wheelock, C. E., D'Amico A., Montuschi P. (ORCID:0000-0001-5589-1750), and Mores N. (ORCID:0000-0002-4197-0914)

Published
2010

19. Immunoproteomic Analysis of the Development of Natural Immunity in Subjects Colonized by Neisseria meningitidisReveals Potential Vaccine Candidates

Author

Williams, Jeannette N., Skipp, Paul J., O'Connor, C. David, Christodoulides, Myron, and Heckels, John E.

Abstract

ABSTRACTThe potential protective effect of existing vaccines against serogroup B meningococci, based on outer membrane proteins, is limited by strain restriction and apparent short duration of immune responses. In contrast, meningococcal colonization is known to stimulate the production of cross-protective antibodies as defined by the development of serum bactericidal activity (SBA) against heterologous serogroup B strains. In the current study, a resource of human serum samples and meningococcal carriage strains from studies of longitudinal carriage has been subjected to immunoproteomic analysis to investigate the outer membrane protein antigens associated with the development of SBA to both homologous and heterologous meningococcal serogroup B strains. Proteins from outer membranes of homologous and heterologous strains were separated by two-dimensional electrophoresis and reacted with paired sera which showed an increase in SBA following colonization. Individuals showed differing patterns of reactivity upon colonization, with an increase in SBA being associated with increases in the number of spots detected before and after colonization and/or with increases in the intensity of individual spots. Analysis of immunoreactive spots by mass spectrometry resulted in the identification of 43 proteins potentially associated with the development of SBA against both homologous and heterologous strains. The list of protein immunogens generated included not only well-established antigens but also novel proteins that represent potentially new candidates for inclusion in defined, multicomponent serogroup B vaccines.

Published
2009
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20. Immunoproteomic Analysis of the Development of Natural Immunity in Subjects Colonized by Neisseria meningitidis Reveals Potential Vaccine Candidates

Author

Williams, Jeannette N., Skipp, Paul J., O'Connor, C. David, Christodoulides, Myron, and Heckels, John E.

Abstract

The potential protective effect of existing vaccines against serogroup B meningococci, based on outer membrane proteins, is limited by strain restriction and apparent short duration of immune responses. In contrast, meningococcal colonization is known to stimulate the production of cross-protective antibodies as defined by the development of serum bactericidal activity (SBA) against heterologous serogroup B strains. In the current study, a resource of human serum samples and meningococcal carriage strains from studies of longitudinal carriage has been subjected to immunoproteomic analysis to investigate the outer membrane protein antigens associated with the development of SBA to both homologous and heterologous meningococcal serogroup B strains. Proteins from outer membranes of homologous and heterologous strains were separated by two-dimensional electrophoresis and reacted with paired sera which showed an increase in SBA following colonization. Individuals showed differing patterns of reactivity upon colonization, with an increase in SBA being associated with increases in the number of spots detected before and after colonization and/or with increases in the intensity of individual spots. Analysis of immunoreactive spots by mass spectrometry resulted in the identification of 43 proteins potentially associated with the development of SBA against both homologous and heterologous strains. The list of protein immunogens generated included not only well-established antigens but also novel proteins that represent potentially new candidates for inclusion in defined, multicomponent serogroup B vaccines.

Published
2009

21. Proteomic Analysis of Outer Membranes and Vesicles from Wild-Type Serogroup B Neisseria meningitidis and a Lipopolysaccharide-Deficient Mutant

Author

Williams, Jeannette N., Skipp, Paul J., Humphries, Holly E., Christodoulides, Myron, O'Connor, C. David, and Heckels, John E.

Abstract

Current experimental vaccines against serogroup B Neisseria meningitidis are based on meningococcal outer membrane (OM) proteins present in outer membrane vesicles (OMV) in which toxic lipopolysaccharide is depleted by detergent extraction. Knowledge of the composition of OM and OMV is essential for developing new meningococcal vaccines based on defined antigens. In the current study, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and nanocapillary liquid chromatography-tandem mass spectrometry were used to investigate the proteomes of OM and OMV from meningococcal strain MC58 and OM from a lipopolysaccharide-deficient mutant. The analysis of OM revealed a composition that was much more complex than the composition that has been reported previously; a total of 236 proteins were identified, only 6.4% of which were predicted to be located in the outer membrane. The most abundant proteins included not only the well-established major OM proteins (PorA, PorB, Opc, Rmp, and Opa) but also other proteins, such as pilus-associated protein Q (PilQ) and a putative macrophage infectivity protein. All of these proteins were also present in OMV obtained by extraction of the OM with deoxycholate. There were markedly increased levels of some additional proteins in OM from the lipopolysaccharide-deficient mutant, including enzymes that contribute to the tricarboxylic acid cycle. In all the preparations, the proteins not predicted to have an OM location were predominantly periplasmic or cytoplasmic or had an unknown location, and relatively few cytoplasmic membrane proteins were detected. However, several proteins that have previously been identified as potential vaccine candidates were not detected in either OM preparations or in OMV. These results have important implications for the development and use of vaccines based on outer membrane proteins.

Published
2007

22. Proteomic Analysis of Outer Membranes and Vesicles from Wild-Type Serogroup B Neisseria meningitidisand a Lipopolysaccharide-Deficient Mutant

Author

Williams, Jeannette N., Skipp, Paul J., Humphries, Holly E., Christodoulides, Myron, O'Connor, C. David, and Heckels, John E.

Abstract

ABSTRACTCurrent experimental vaccines against serogroup B Neisseria meningitidisare based on meningococcal outer membrane (OM) proteins present in outer membrane vesicles (OMV) in which toxic lipopolysaccharide is depleted by detergent extraction. Knowledge of the composition of OM and OMV is essential for developing new meningococcal vaccines based on defined antigens. In the current study, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and nanocapillary liquid chromatography-tandem mass spectrometry were used to investigate the proteomes of OM and OMV from meningococcal strain MC58 and OM from a lipopolysaccharide-deficient mutant. The analysis of OM revealed a composition that was much more complex than the composition that has been reported previously; a total of 236 proteins were identified, only 6.4% of which were predicted to be located in the outer membrane. The most abundant proteins included not only the well-established major OM proteins (PorA, PorB, Opc, Rmp, and Opa) but also other proteins, such as pilus-associated protein Q (PilQ) and a putative macrophage infectivity protein. All of these proteins were also present in OMV obtained by extraction of the OM with deoxycholate. There were markedly increased levels of some additional proteins in OM from the lipopolysaccharide-deficient mutant, including enzymes that contribute to the tricarboxylic acid cycle. In all the preparations, the proteins not predicted to have an OM location were predominantly periplasmic or cytoplasmic or had an unknown location, and relatively few cytoplasmic membrane proteins were detected. However, several proteins that have previously been identified as potential vaccine candidates were not detected in either OM preparations or in OMV. These results have important implications for the development and use of vaccines based on outer membrane proteins.

Published
2007
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23. Sputum proteomic signature of gastro-oesophageal reflux in patients with severe asthma.

Author

Tariq K, Schofield JPR, Nicholas BL, Burg D, Brandsma J, Bansal AT, Wilson SJ, Lutter R, Fowler SJ, Bakke, Caruso M, Dahlen B, Horváth I, Krug N, Montuschi P, Sanak M, Sandström T, Geiser T, Pandis I, Sousa AR, Adcock IM, Shaw DE, Auffray C, Howarth PH, Sterk PJ, Chung KF, Skipp PJ, Dimitrov B, and Djukanović R

Subjects
Adult, Asthma epidemiology, Asthma psychology, Endopeptidases metabolism, European Union organization & administration, Female, Gastroesophageal Reflux diagnosis, Gastroesophageal Reflux epidemiology, Humans, Immunoglobulin lambda-Chains metabolism, Lipocalin 1 metabolism, Male, Middle Aged, Prevalence, Prospective Studies, Protease Inhibitors metabolism, Quality of Life, Severity of Illness Index, Asthma complications, Asthma metabolism, Gastroesophageal Reflux complications, Proteomics methods, Sputum metabolism
Abstract

Gastro-oesophageal reflux disease (GORD) has long been associated with poor asthma control without an established cause-effect relationship. 610 asthmatics (421 severe/88 mild-moderate) and 101 healthy controls were assessed clinically and a subset of 154 severe asthmatics underwent proteomic analysis of induced sputum using untargeted mass spectrometry, LC-IMS-MS E . Univariate and multiple logistic regression analyses (MLR) were conducted to identify proteins associated with GORD in this cohort. When compared to mild/moderate asthmatics and healthy individuals, respectively, GORD was three- and ten-fold more prevalent in severe asthmatics and was associated with increased asthma symptoms and oral corticosteroid use, poorer quality of life, depression/anxiety, obesity and symptoms of sino-nasal disease. Comparison of sputum proteomes in severe asthmatics with and without active GORD showed five differentially abundant proteins with described roles in anti-microbial defences, systemic inflammation and epithelial integrity. Three of these were associated with active GORD by multiple linear regression analysis: Ig lambda variable 1-47 (p = 0·017) and plasma protease C1 inhibitor (p = 0·043), both in lower concentrations, and lipocalin-1 (p = 0·034) in higher concentrations in active GORD. This study provides evidence which suggests that reflux can cause subtle perturbation of proteins detectable in the airways lining fluid and that severe asthmatics with GORD may represent a distinct phenotype of asthma., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Published
2019
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