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1. IL-17–high asthma with features of a psoriasis immunophenotype

Author

Adcock, I.M., Ahmed, H., Auffray, C., Bakke, P., Bansal, A.T., Baribaud, F., Bates, S., Bel, E.H., Bigler, J., Bisgaard, H., Boedigheimer, M.J., Bønnelykke, 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., Horváth, I., Howarth, P., James, A.J., Knowles, R., Knox, A.J., Krug, N., Lefaudeux, D., Loza, M.J., Lutter, R., Manta, A., Masefield, S., 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., Praticò, G., Rao, M. Puig 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., Aliprantis, Antonios, Allen, David, Alving, Kjell, Badorrek, P., Balgoma, David, Ballereau, S., Barber, Clair, Batuwitage, Manohara Kanangana, Bautmans, A., Bedding, A., Behndig, A.F., Beleta, Jorge, Berglind, A., Berton, A., Bochenek, Grazyna, Braun, Armin, Campagna, D., Carayannopoulos, Leon, Casaulta, C., Chaleckis, Romanas, Dahlén, B., Davison, imothy, De Alba, Jorge, De Lepeleire, Inge, Dekker, Tamara, Delin, Ingrid, Dennison, P., Dijkhuis, Annemiek, Dodson, Paul, Draper, Aleksandra, Dyson, K., Edwards, Jessica, El Hadjam, L., Emma, Rosalia, Ericsson, Magnus, Faulenbach, C., Flood, Breda, Galffy, G., Gallart, Hector, Garissi, D., Gent, J., Gerhardsson de Verdier, M., Gibeon, D., Gomez, Cristina, Gove, Kerry, Gozzard, Neil, Guillmant-Farry, E., Henriksson, E., Hewitt, Lorraine, Hoda, U., Hu, Richard, Hu, Sile, Hu, X., Jeyasingham, E., Johnson, K., Jullian, N., Kamphuis, Juliette, Kennington, Erika J., Kerry, Dyson, Kerry, G., Klüglich, M., Knobel, Hugo, Kolmert, Johan, Konradsen, J.R., Kots, Maxim, Kretsos, Kosmas, Krueger, L., Kuo, Scott, Kupczyk, Maciej, Lambrecht, Bart, Lantz, A.-S., Larminie, Christopher, Larsson, L.X., Latzin, P., Lazarinis, N., Lemonnier, N., Lone-Latif, Saeeda, Lowe, L.A., Manta, Alexander, Marouzet, Lisa, Martin, Jane, Mathon, Caroline, McEvoy, L., Meah, Sally, Menzies-Gow, A., Metcalf, Leanne, Mikus, Maria, Monk, Philip, Naz, Shama, Nething, K., Nicholas, Ben, Nihlén, U., Nilsson, Peter, Niven, R., Nordlund, B., Nsubuga, S., Pacino, Antonio, Palkonen, Susanna, Pellet, J., Pennazza, Giorgio, Petrén, Anne, Pink, Sandy, Pison, C., Postle, Anthony, Rahman-Amin, Malayka, Ravanetti, Lara, Ray, Emma, Reinke, Stacey, Reynolds, Leanne, Riemann, K., Robberechts, Martine, Rocha, J.P., Rossios, C., Russell, Kirsty, Rutgers, Michael, Santini, G., Santoninco, Marco, Saqi, M., Schoelch, Corinna, Schofield, James P.R., Scott, S., Sehgal, N., Sjödin, Marcus, Smids, Barbara, Smith, Caroline, Smith, Jessica, Smith, Katherine M., Söderman, P., Sogbessan, A., Spycher, F., Staykova, Doroteya, Stephan, S., Stokholm, J., Strandberg, K., Sunther, M., Szentkereszty, M., Tamasi, L., Tariq, K., Thörngren, John-Olof, Thorsen, Jonathan, Valente, S., van de Pol, Marianne, van Drunen, C.M., Van Eyll, Jonathan, Versnel, Jenny, Vink, Anton, von Garnier, C., Vyas, A., Wald, Frans, Walker, Samantha, Ward, Jonathan, Wetzel, Kristiane, Wiegman, Coen, Williams, Siân, Yang, Xian, Yeyasingham, Elizabeth, Amgen, W. Yu, Zetterquist, W., Zolkipli, Z., Zwinderman, A.H., Östling, Jörgen, van Geest, Marleen, Jevnikar, Zala, Wilson, Susan, Lutter, Rene, Shaw, Dominick E., Bakke, Per S., Caruso, Massimo, Dahlen, Sven-Erik, Fowler, Stephen J., Horváth, Ildikó, 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., Djukanović, Ratko, and Vaarala, Outi

Published
2019
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3. SCIENCE AND SOCIETY: The RA-MAP Consortium: a working model for academia-industry collaboration

Author

Cope, Andrew P., Barnes, Michael R., Belson, Alexandra, Binks, Michael, Brockbank, Sarah, Bonachela-Capdevila, Francisco, Carini, Claudio, Fisher, Benjamin A., Goodyear, Carl S., Emery, Paul, Ehrenstein, Michael R., Gozzard, Neil, Harris, Ray, Hollis, Sally, Keidel, Sarah, Levesque, Marc, Lindholm, Catharina, McDermott, Michael F., McInnes, Iain B., Mela, Christopher M., Parker, Gerry, Read, Simon, Pedersen, Ayako Wakatsuki, Ponchel, Frederique, Porter, Duncan, Rao, Ravi, Rowe, Anthony, Schulze-Knappe, Peter, Sleeman, Matthew A., Symmons, Deborah, Taylor, Peter C., Tom, Brian, Tsuji, Wayne, Verbeeck, Denny, and Isaacs, John D.

Published
2018
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4. RA-MAP, molecular immunological landscapes in early rheumatoid arthritis and healthy vaccine recipients

Author

Isaacs, John D., Brockbank, Sarah, Pedersen, Ayako Wakatsuki, Hilkens, Catharien, Anderson, Amy, Stocks, Philip, Lendrem, Dennis, Tarn, Jessica, Smith, Graham R., Allen, Ben, Casement, John, Diboll, Julie, Harry, Rachel, Cooles, Faye A. H., Cope, Andrew P., Simpson, Gemma, Toward, Ruth, Noble, Hayley, Parke, Angela, Wu, Wing, Clarke, Fiona, Scott, David, Scott, Ian C., Galloway, James, Lempp, Heidi, Ibrahim, Fowzia, Schwank, Samana, Molyneux, Gemma, Lazarov, Tomi, Geissmann, Frederic, Goodyear, Carl S., McInnes, Iain B., Donnelly, Iona, Gilmour, Ashley, Virlan, Aysin Tulunay, Porter, Duncan, Ponchel, Frederique, Emery, Paul, El-Jawhari, Jehan, Parmar, Rekha, McDermott, Michael F., Fisher, Benjamin A., Young, Steve P., Jones, Philip, Raza, Karim, Filer, Andrew, Pitzalis, Costantino, Barnes, Michael R., Watson, David S., Henkin, Rafael, Thorborn, Georgina, Fossati-Jimack, Liliane, Kelly, Stephen, Humby, Frances, Bombardieri, Michele, Rana, Sharmila, Jia, Zhilong, Goldmann, Katriona, Lewis, Myles, Ng, Sandra, Barbosa-Silva, Adriano, Tzanis, Evan, Gallagher-Syed, Amaya, John, Christopher R., Ehrenstein, Michael R., Altobelli, Gioia, Martins, Sandra, Nguyen, Dao, Ali, Humayara, Ciurtin, Coziana, Buch, Maya, Symmons, Deborah, Worthington, Jane, Bruce, Ian N., Sergeant, Jamie C., Verstappen, Suzanne M. M., Stirling, Fiona, Hughes-Morley, Adwoa, Tom, Brian, Farewell, Vernon, Zhong, Yujie, Taylor, Peter C., Buckley, Christopher D., Keidel, Sarah, Cuff, Carolyn, Levesque, Marc, Long, Andrew, Liu, Zheng, Lipsky, Samantha, Harvey, Bohdan, Macoritto, Michael, Hong, Feng, Kaymakcalan, Sukru, Tsuji, Wayne, Sabin, Tony, Ward, Neil, Talbot, Susan, Padhji, Desmond, Sleeman, Matthew, Finch, Donna, Herath, Athula, Lindholm, Catharina, Jenkins, Martin, Ho, Meilien, Hollis, Sally, Marshall, Chris, Parker, Gerry, Page, Matt, Edwards, Hannah, Cuza, Alexandru, Gozzard, Neil, Pandis, Ioannis, Rowe, Anthony, Capdevila, Francisco Bonachela, Loza, Matthew J., Curran, Mark, Verbeeck, Denny, Dan Baker, Mela, Christopher M., Vranic, Ivana, Mela, Catherine T., Wright, Stephen, Rowell, Lucy, Vernon, Emma, Joseph, Nina, Payne, Neil, Rao, Ravi, Binks, Michael, Belson, Alexandra, Ludbrook, Valerie, Hicks, Kirsty, Tipney, Hannah, Ellis, Joanne, Hasan, Samiul, Didierlaurent, Arnaud, Burny, Wivine, Haynes, Andrea, Larminie, Chris, Harris, Ray, Dastros-Pitei, Daniela, Carini, Claudio, Kola, Blerina, Jelinsky, Scott, Hodge, Martin, Maciejewski, Mateusz, Ziemek, Daniel, Schulz-Knappe, Peter, Zucht, Hans-Dieter, Budde, Petra, Coles, Mark, Butler, James A., Read, Simon, and Consortium, The RA-MAP

Subjects
Arthritis, Rheumatoid, Proteomics, Statistics and Probability, Vaccines, Humans, Library and Information Sciences, Statistics, Probability and Uncertainty, Monocytes, Autoantibodies, Biological Specimen Banks, Computer Science Applications, Education, Information Systems
Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of early, drug naive RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into immune-mediated disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA.

Published
2022

5. Stratification of asthma phenotypes by airway proteomic signatures

Author

Schofield, James P. R., Burg, Dominic, Nicholas, Ben, Strazzeri, Fabio, Brandsma, Joost, Staykova, Doroteya, Folisi, Caterina, Bansal, Aruna T., Xian, Yang, Guo, Yike, Rowe, Anthony, Corfield, Julie, Wilson, Susan, Ward, Jonathan, Lutter, Rene, Shaw, Dominick E., Bakke, Per S., Caruso, Massimo, Dahlen, Sven-Erik, Fowler, Stephen J., Horvath, Ildiko, Howarth, Peter, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandstrom, Thomas, Sun, Kai, Pandis, Ioannis, Riley, John, Auffray, Charles, De Meulder, Bertrand, Lefaudeux, Diane, Sousa, Ana R., Adcock, Ian M., Chung, Kian Fan, Sterk, Peter J., Skipp, Paul J., Djukanovic, Ratko, Ahmed, H., Allen, D., Badorrek, P., Ballereau, S., Baribaud, F., Batuwitage, M. K., Bedding, A., Behndig, A. F., Berglind, A., Berton, A., Bigler, J., Boedigheimer, M. J., Bonnelykke, K., Brinkman, P., Bush, A., Campagna, D., Casaulta, C., Chaiboonchoe, A., Davison, T., De Meulder, B., Delin, I., Dennison, P., Dodson, P., El Hadjam, L., Erzen, D., Faulenbach, C., Fichtner, K., Fitch, N., Formaggio, E., Gahlemann, M., Galffy, G., Garissi, D., Garret, T., Gent, J., Guillmant-Farry, E., Henriksson, E., Hoda, U., Hohlfeld, J. M., Hu, X., James, A., Johnson, K., Jullian, N., Kerry, G., Klueglich, M., Knowles, R., Konradsen, J. R., Kretsos, K., Krueger, L., Lantz, A. -S, Larminie, C., Latzin, P., Lefaudeux, D., Lemonnier, N., Lowe, L. A., Lutter, R., Manta, A., Mazein, A., McEvoy, L., Menzies-Gow, A., Mores, N., Murray, C. S., Nething, K., Nihlen, U., Niven, R., Nordlund, B., Nsubuga, S., Pellet, J., Pison, C., Pratico, G., Puig Valls, M., Riemann, K., Rocha, J. P., Rossios, C., Santini, G., Saqi, M., Scott, S., Sehgal, N., Selby, A., Soderman, P., Sogbesan, A., Spycher, F., Stephan, S., Stokholm, J., Sunther, M., Szentkereszty, M., Tamasi, L., Tariq, K., Valente, S., van Aalderen, W. M., van Drunen, C. M., Van Eyll, J., Vyas, A., Yu, W., Zetterquist, W., Zolkipli, Z., Zwinderman, A. H., Adriaens, Nora, Aliprantis, Antonios, Alving, Kjell, Bakke, Per, Balgoma, David, Barber, Clair, Baribaud, Frederic, Bates, Stewart, Bautmans, An, Beleta, Jorge, Bochenek, Grazyna, Braun, Armin, Carayannopoulos, Leon, Rocha, Joao Pedro Carvalho da Purificacao, Chaleckis, Romanas, D'Amico, Arnaldo, De Alba, Jorge, De Lepeleire, Inge, Dekker, Tamara, Dijkhuis, Annemiek, Draper, Aleksandra, Edwards, Jessica, Emma, Rosalia, Ericsson, Magnus, Flood, Breda, Gallart, Hector, Gomez, Cristina, Gove, Kerry, Gozzard, Neil, Haughney, John, Hewitt, Lorraine, Hohlfeld, Jens, Holweg, Cecile, Hu, Richard, Hu, Sile, Kamphuis, Juliette, Kennington, Erika J., Kerry, Dyson, Knobel, Hugo, Kolmert, Johan, Kots, Maxim, Kuo, Scott, Kupczyk, Maciej, Lambrecht, Bart, Lone-Latif, Saeeda, Loza, Matthew J., Marouzet, Lisa, Martin, Jane, Masefield, Sarah, Mathon, Caroline, Meah, Sally, Meiser, Andrea, Metcalf, Leanne, Mikus, Maria, Miralpeix, Montse, Monk, Philip, Naz, Shama, Nilsson, Peter, Ostling, Jorgen, Pacino, Antonio, Palkonen, Susanna, Pavlidis, Stelios, Pennazza, Giorgio, Petren, Anne, Pink, Sandy, Postle, Anthony, Powell, Pippa, Rahman-Amin, Malayka, Rao, Navin, Ravanetti, Lara, Ray, Emma, Reinke, Stacey, Reynolds, Leanne, Robberechts, Martine, Roberts, Amanda, Russell, Kirsty, Rutgers, Michael, Santoninco, Marco, Schoelch, Corinna, Sjodin, Marcus, Smids, Barbara, Smith, Caroline, Smith, Jessica, Smith, Katherine M., Thorngren, John-Olof, Thornton, Bob, Thorsen, Jonathan, van de Pol, Marianne, van Geest, Marleen, Versnel, Jenny, Vink, Anton, Wald, Frans, Walker, Samantha, Weiszhart, Zsoka, Wetzel, Kristiane, Wheelock, Craig E., Wiegman, Coen, Williams, Sian, Wilson, Susan J., Woodcock, Ashley, Yang, Xian, Yeyasingham, Elizabeth, Prins, Jan-Bas, Gahlemann, Martina, Visintin, Luigi, Evans, Hazel, Puhl, Martine, Buzermaniene, Lina, Hudson, Val, Bond, Laura, de Boer, Pim, Widdershoven, Guy, Sigmund, Ralf, Supple, David, Hamerlijnck, Dominique, Negus, Jenny, Kamphuis, Julitte, Sergison, Lehanne, Onstein, Susanne, MacNee, William, Bernardini, Renato, Bont, Louis, Wecksell, Per-Ake, Graduate School, AII - Inflammatory diseases, Pulmonology, Ear, Nose and Throat, Epidemiology and Data Science, APH - Methodology, Publica, and Commission of the European Communities

Subjects
0301 basic medicine, Male, Proteomics, Allergy, Proteome, Neutrophils, Respiratory Medicine and Allergy, Transcriptome, 0302 clinical medicine, neutrophils, Forced Expiratory Volume, Immunology and Allergy, CD44, 610 Medicine & health, Lungmedicin och allergi, phenotypes, Middle Aged, medicine.anatomical_structure, Phenotype, 1107 Immunology, Female, eosinophils, medicine.symptom, Life Sciences & Biomedicine, Adult, Settore BIO/14 - FARMACOLOGIA, Immunology, Computational biology, 03 medical and health sciences, Young Adult, proteomics, Eosinophilia, medicine, Humans, U-BIOPRED Study Group, Asthma, Aged, Science & Technology, Microarray analysis techniques, business.industry, Sputum, biomarkers, DEGRADATION, Eosinophil, medicine.disease, Eosinophils, EXACERBATIONS, 030104 developmental biology, 030228 respiratory system, business
Abstract

Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms. Objective: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification. Methods: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. Results: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. Conclusion: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies. asthma proteomics biomarkers eosinophils neutrophils

Published
2019

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

Author

Perotin, Jeanne-Marie, Schofield, James PR, 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, IM, Ahmed, H, Auffray, C, Bakke, P, Banssal, AT, Baribaud, F, Bates, S, Bel, EH, Bigler, J, Bisgaard, H, Boedigheimer, MJ, Bonnelykke, K, Brandsma, J, Brinkman, P, Bucchioni, E, Burg, D, Bush, A, Caruso, M, Chaiboonchoe, A, Chanez, P, Chung, KF, Compton, CH, Corfield, J, D'Amico, A, Dahlen, SE, De Meulder, B, Djukanovic, R, Erpenbeck, VJ, Erzen, D, Fichtner, K, Fitch, N, Fleming, LJ, Formaggio, E, Fowler, SJ, Frey, U, Gahlemann, M, Geiser, T, Guo, Y, Hashimoto, S, Haughney, J, Hedlin, G, Hekking, PW, Higenbottam, T, Hohlfeld, JM, Holweg, C, Horvath, I, Howarth, P, James, AJ, Knowles, R, Knox, AJ, Krug, N, Lefaudeux, D, Loza, MJ, Lutter, R, Manta, A, Masefield, S, Matthews, JG, Mazein, A, Meiser, A, Middelveld, RJM, Miralpeix, M, Montuschi, P, Mores, N, Murray, CS, 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, DE, Sigmund, R, Singer, F, Skipp, PJ, Sousa, AR, Sterk, PJ, Sun, K, Thornton, B, van Aalderen, WM, van Geest, M, Vestbo, J, Vissing, NH, Wagener, AH, Wagers, SS, Weiszhart, Z, Wheelock, CE, Wilson, SJ, Aliprantis, Antonios, Allen, David, Alving, Kjell, Badorrek, P, Balgoma, David, Ballereau, S, Barber, Clair, Batuwitage, Manohara Kanangana, Bautmans, An, Bedding, A, Behndig, AF, 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., Gerhardsson de Verdier, M, 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, EJ, Kerry, D, Kerry, G, Klueglich, M, Knobel, H, Kolmert, Johan, Konradsen, JR, Kots, M, Kretsos, Kosmas, Krueger, L, Kuo, S, Kupczyk, M, Lambrecht, Bart, Lantz, A-S, Larminie, Christopher, Larsson, LX, Latzin, P, Lazarinis, N, Lemonnier, N, Lone-Latif, S, Lowe, LA, 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, JP, Rossios, C, Russell, K, Rutgers, M, Santini, G, Santoninco, M, Saqi, M, Schoelch, C, Schofield, JPR, Scott, S, Sehgal, N, Sjodin, M, Smids, B, Smith, Caroline, Smith, J, Smith, KM, 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, CM, 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, AH, 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, Commission of the European Communities, Publica, Pulmonology, AII - Inflammatory diseases, Ear, Nose and Throat, Epidemiology and Data Science, APH - Methodology, and NIHR Southampton Biomedical Research Centre

Subjects
severe asthma, Pulmonary and Respiratory Medicine, endotyping, Gastrointestinal, phenotyping, Settore BIO/14 - FARMACOLOGIA, [SDV]Life Sciences [q-bio], Respiratory System, ROWE, Gene Expression, Article, Endoscopy, Gastrointestinal, Epithelium, CCN Intercellular Signaling Proteins, Patent application, 03 medical and health sciences, 0302 clinical medicine, Shareholder, gatroesophageal reflux, Nothing, Proto-Oncogene Proteins, Medicine and Health Sciences, Humans, Medicine, Obesity, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, 11 Medical and Health Sciences, U-BIOPRED Study Group, Science & Technology, business.industry, U-BIOPRED, digestive, oral, and skin physiology, Airway inflammation, Conflict of interest, Biology and Life Sciences, Endoscopy, Asthma, digestive system diseases, 3. Good health, 030228 respiratory system, Spin out, Case-Control Studies, Law, Honorarium, Gastroesophageal Reflux, business, Life Sciences & Biomedicine
Abstract

Gastro-oesophageal reflux disease (GORD) and obesity are associated with frequent exacerbations and poor quality of life in asthmatics. Multiple mechanisms have been proposed for the effect of obesity, including modification of inflammation affecting epithelial cell proliferation and wound repair, while the role of GORD is poorly understood and proton pump inhibitor (PPI) are of variable efficacy. GORD might exert a deleterious effect by inducing vagal reflex, neuroinflammation and directly ( via microaspiration) triggering airway inflammation. Studies of reflux in animal models and human bronchial epithelial cell culture show varying impact on inflammation and airway remodelling. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr PEROTIN has nothing to disclose. Conflict of interest: Dr Schofield has nothing to disclose. Conflict of interest: Dr Wilson has nothing to disclose. Conflict of interest: Dr Ward has nothing to disclose. Conflict of interest: Dr Brandsma has nothing to disclose. Conflict of interest: Dr Strazzeri has nothing to disclose. Conflict of interest: Dr Bansal has nothing to disclose. Conflict of interest: Dr Yang has nothing to disclose. Conflict of interest: Dr Rowe reports and a full time employee and shareholder of Janssen Pharmaceutical Companies of Johnson and Johnson. Conflict of interest: Miss Corfield has nothing to disclose. Conflict of interest: Dr Lutter has nothing to disclose. Conflict of interest: Prof. Shaw reports personal fees and non-financial support from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Novartis, personal fees from Teva, personal fees from Circassia, and a grant from GSK, outside the submitted work. Conflict of interest: Dr Bakke reports personal fees from GSK, AZ, Novartis andTeva, outside the submitted work. Conflict of interest: MC have no conflict of interest to disclose. Conflict of interest: Dr Dahlen has nothing to disclose. Conflict of interest: Dr Fowler reports personal fees and non-financial support from AstraZeneca, grants and personal fees from Boehringer Ingelheim, personal fees from Novartis, personal fees from Teva, outside the submitted work. Conflict of interest: Dr Horvath reports personal fees from Astra Zeneca, Boehringer Ingelheim, Novartis, CSL, Chiesi, Roche, GSK, Berlin-Chemie and Sandoz, outside the submitted work. Conflict of interest: Dr Howarth reports personal fees from GSK, outside the submitted work. Conflict of interest: Dr Krug has nothing to disclose. Conflict of interest: Dr Montuschi has nothing to disclose. Conflict of interest: Dr Sanak has nothing to disclose. Conflict of interest: Dr Sandstrom reports other monetary support from Boehringer Ingelheim, outside the submitted work. Conflict of interest: Dr Sun has nothing to disclose. Conflict of interest: Dr Pandis has nothing to disclose. Conflict of interest: Dr Auffray reports grants from Innovative Medicine Initiative, during the conduct of the study. Conflict of interest: Dr De Meulder reports grants from Innovative Medicine Initiative, during the conduct of the study. Conflict of interest: Ms. Lefaudeux reports grants from Innovative Medicine Initiative, grants from Innovative Medicine Initiative, during the conduct of the study. Conflict of interest: Dr Riley reports and I have shares in and I am employed by GSK. Conflict of interest: Dr Sousa has nothing to disclose. Conflict of interest: Dr Dahlen has nothing to disclose. Conflict of interest: Dr Adcock reports grants from EU-IMI, during the conduct of the study. Conflict of interest: KFC has received honoraria for participating in Advisory Board meetings of GSK, AZ, BI, Teva, Novartis and Merck regarding treatments for asthma and chronic obstructive pulmonary disease and has also been renumerated for speaking engagements. Conflict of interest: Dr Sterk reports grants from Innovative Medicines Initiative, during the conduct of the study. Conflict of interest: Dr Skipp has nothing to disclose. Conflict of interest: Dr Collins reports a patent application for use of a genetically modified Drosophila line carrying one or more mammalian genes associated with a chronic respiratory disease and uses to screen the impact of such genes. Conflict of interest: Dr Davies has nothing to disclose. Conflict of interest: Dr Djukanovic reports receiving fees for lectures at symposia organised by Novartis, AstraZeneca and TEVA, consultation for TEVA and Novartis as member of advisory boards, and participation in a scientific discussion about asthma organised by GlaxoSmithKline. He is a co-founder and current consultant, and has shares in Synairgen, a University of Southampton spin out company.

Published
2019

8. Novel methodology to discern predictors of remission and patterns of disease activity over time using rheumatoid arthritis clinical trials data

Author

Brockbank, Sarah, Carini, Claudio, Pope, Andrew, Ehrenstein, Michael R., Fisher, Benjamin, Goodyear, Carl S., Gozzard, Neil, Harris, Ray, Hicks, Kirsty, Hollis, Sally, Hughes Morley, Adwoa, Isaacs, John D., Kola, Blerina, McInnes, Iain B, Mela, Christopher M., Parker, Gerry, Wakatsuki Pedersen, Ayako, Ponchel, Frederique, Sabin, Tony, Scott, David L, Scott, Ian C., Sleeman, Matthew A., Symmons, Deborah, Taylor, Peter C., Tom, Brian, Tsuji, Wayne, and Zhong, Yujie

Subjects
musculoskeletal diseases, immune system diseases, skin and connective tissue diseases
Abstract

Objectives To identify predictors of remission and disease activity patterns in patients with rheumatoid arthritis (RA) using individual participant data (IPD) from clinical trials. Methods Phase II and III clinical trials completed between 2002 and 2012 were identified by systematic literature review and contact with UK market authorisation holders. Anonymised baseline and follow-up IPD from nonbiological arms were amalgamated. Multiple imputation was used to handle missing outcome and covariate information. Random effects logistic regression was used to identify predictors of remission, measured by the Disease Activity Score 28 (DAS28) at 6 months. Novel latent class mixed models characterised DAS28 over time. Results IPD of 3290 participants from 18 trials were included. Of these participants, 92% received methotrexate (MTX). Remission rates were estimated at 8.4%(95%CI 7.4%to9.5%) overall, 17%(95%CI 14.8%to19.4%) for MTX-naïve patients with early RA and 3.2% (95% CI 2.4% to 4.3%) for those with prior MTX exposure at entry. In prior MTX-exposed patients, lower baseline DAS28 and MTX reinitiation were associated with remission. In MTX-naïve patients, being young, white, male, with better functional and mental health, lower baseline DAS28 and receiving concomitant glucocorticoids were associated with remission. Three DAS28 trajectory subpopulations were identified in MTX-naïve and MTX-exposed patients. A number of variables were associated with subpopulation membership and DAS28 levels within subpopulations. Conclusions Predictors of remission differed between MTX-naïve and prior MTX-exposed patients at entry. Latent class mixed models supported differential non-biological therapy response, with three distinct trajectories observed in both MTX-naïve and MTX-exposed patients. Findings should be useful when designing future RA trials and interpreting results of biomarker studies.

Published
2018

9. IL-17–high asthma with features of a psoriasis immunophenotype

Author

Östling, Jörgen, primary, van Geest, Marleen, additional, Schofield, James P.R., additional, Jevnikar, Zala, additional, Wilson, Susan, additional, Ward, Jonathan, additional, Lutter, Rene, additional, Shaw, Dominick E., additional, Bakke, Per S., additional, Caruso, Massimo, additional, Dahlen, Sven-Erik, additional, Fowler, Stephen J., additional, Horváth, Ildikó, additional, Krug, Norbert, additional, Montuschi, Paolo, additional, Sanak, Marek, additional, Sandström, Thomas, additional, Sun, Kai, additional, Pandis, Ioannis, additional, Auffray, Charles, additional, Sousa, Ana R., additional, Guo, Yike, additional, Adcock, Ian M., additional, Howarth, Peter, additional, Chung, Kian Fan, additional, Bigler, Jeanette, additional, Sterk, Peter J., additional, Skipp, Paul J., additional, Djukanović, Ratko, additional, Vaarala, Outi, additional, Adcock, I.M., additional, Ahmed, H., additional, Auffray, C., additional, Bakke, P., additional, Bansal, A.T., additional, Baribaud, F., additional, Bates, S., additional, Bel, E.H., additional, Bigler, J., 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, Caruso, M., additional, Chaiboonchoe, A., additional, Chanez, P., additional, Chung, K.F., additional, Compton, C.H., additional, Corfield, J., additional, D'Amico, A., additional, Dahlen, S.E., additional, De Meulder, B., additional, Djukanovic, R., additional, Erpenbeck, V.J., additional, Erzen, D., additional, Fichtner, K., additional, Fitch, N., additional, Fleming, L.J., additional, Formaggio, E., additional, Fowler, S.J., additional, Frey, U., additional, Gahlemann, M., additional, Geiser, T., additional, Guo, Y., additional, Hashimoto, S., additional, Haughney, J., additional, Hedlin, G., additional, Hekking, P.W., additional, Higenbottam, T., additional, Hohlfeld, J.M., additional, Holweg, C., additional, Horváth, I., additional, Howarth, P., additional, James, A.J., additional, Knowles, R., additional, Knox, A.J., additional, Krug, N., additional, Lefaudeux, D., additional, Loza, M.J., additional, Lutter, R., additional, Manta, A., additional, Masefield, S., additional, Mazein, A., additional, Meiser, A., additional, Middelveld, R.J.M., additional, Miralpeix, M., additional, Montuschi, P., additional, Mores, N., additional, Murray, C.S., additional, Musial, J., additional, Myles, D., additional, Pahus, L., additional, Pandis, I., additional, Pavlidis, S., additional, Powell, P., additional, Praticò, G., additional, Rao, M. Puig N., additional, Riley, J., additional, Roberts, A., additional, Roberts, G., additional, Rowe, A., additional, Sandström, T., additional, Seibold, W., additional, Selby, A., additional, Shaw, D.E., additional, Sigmund, R., additional, Singer, F., additional, Skipp, P.J., additional, Sousa, A.R., additional, Sterk, P.J., additional, Sun, K., additional, Thornton, B., 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, Wheelock, C.E., additional, Wilson, S.J., additional, Aliprantis, Antonios, additional, Allen, David, additional, Alving, Kjell, additional, Badorrek, P., additional, Balgoma, David, additional, Ballereau, S., additional, Barber, Clair, additional, Batuwitage, Manohara Kanangana, additional, Bautmans, A., additional, Bedding, A., additional, Behndig, A.F., additional, Beleta, Jorge, additional, Berglind, A., additional, Berton, A., additional, Bochenek, Grazyna, additional, Braun, Armin, additional, Campagna, D., additional, Carayannopoulos, Leon, additional, Casaulta, C., additional, Chaleckis, Romanas, additional, Dahlén, B., additional, Davison, imothy, additional, De Alba, Jorge, additional, De Lepeleire, Inge, additional, Dekker, Tamara, additional, Delin, Ingrid, additional, Dennison, P., additional, Dijkhuis, Annemiek, additional, Dodson, Paul, additional, Draper, Aleksandra, additional, Dyson, K., additional, Edwards, Jessica, additional, El Hadjam, L., additional, Emma, Rosalia, additional, Ericsson, Magnus, additional, Faulenbach, C., additional, Flood, Breda, additional, Galffy, G., additional, Gallart, Hector, additional, Garissi, D., additional, Gent, J., additional, Gerhardsson de Verdier, M., additional, Gibeon, D., additional, Gomez, Cristina, additional, Gove, Kerry, additional, Gozzard, Neil, additional, Guillmant-Farry, E., additional, Henriksson, E., additional, Hewitt, Lorraine, additional, Hoda, U., additional, Hu, Richard, additional, Hu, Sile, additional, Hu, X., additional, Jeyasingham, E., additional, Johnson, K., additional, Jullian, N., additional, Kamphuis, Juliette, additional, Kennington, Erika J., additional, Kerry, Dyson, additional, Kerry, G., additional, Klüglich, M., additional, Knobel, Hugo, additional, Kolmert, Johan, additional, Konradsen, J.R., additional, Kots, Maxim, additional, Kretsos, Kosmas, additional, Krueger, L., additional, Kuo, Scott, additional, Kupczyk, Maciej, additional, Lambrecht, Bart, additional, Lantz, A.-S., additional, Larminie, Christopher, additional, Larsson, L.X., additional, Latzin, P., additional, Lazarinis, N., additional, Lemonnier, N., additional, Lone-Latif, Saeeda, additional, Lowe, L.A., additional, Manta, Alexander, additional, Marouzet, Lisa, additional, Martin, Jane, additional, Mathon, Caroline, additional, McEvoy, L., additional, Meah, Sally, additional, Menzies-Gow, A., additional, Metcalf, Leanne, additional, Mikus, Maria, additional, Monk, Philip, additional, Naz, Shama, additional, Nething, K., additional, Nicholas, Ben, additional, Nihlén, U., additional, Nilsson, Peter, additional, Niven, R., additional, Nordlund, B., additional, Nsubuga, S., additional, Pacino, Antonio, additional, Palkonen, Susanna, additional, Pellet, J., additional, Pennazza, Giorgio, additional, Petrén, Anne, additional, Pink, Sandy, additional, Pison, C., additional, Postle, Anthony, additional, Rahman-Amin, Malayka, additional, Ravanetti, Lara, additional, Ray, Emma, additional, Reinke, Stacey, additional, Reynolds, Leanne, additional, Riemann, K., additional, Robberechts, Martine, additional, Rocha, J.P., additional, Rossios, C., additional, Russell, Kirsty, additional, Rutgers, Michael, additional, Santini, G., additional, Santoninco, Marco, additional, Saqi, M., additional, Schoelch, Corinna, additional, Scott, S., additional, Sehgal, N., additional, Sjödin, Marcus, additional, Smids, Barbara, additional, Smith, Caroline, additional, Smith, Jessica, additional, Smith, Katherine M., additional, Söderman, P., additional, Sogbessan, A., additional, Spycher, F., additional, Staykova, Doroteya, additional, Stephan, S., additional, Stokholm, J., additional, Strandberg, K., additional, Sunther, M., additional, Szentkereszty, M., additional, Tamasi, L., additional, Tariq, K., additional, Thörngren, John-Olof, additional, Thorsen, Jonathan, additional, Valente, S., additional, van de Pol, Marianne, additional, van Drunen, C.M., additional, Van Eyll, Jonathan, additional, Versnel, Jenny, additional, Vink, Anton, additional, von Garnier, C., additional, Vyas, A., additional, Wald, Frans, additional, Walker, Samantha, additional, Wetzel, Kristiane, additional, Wiegman, Coen, additional, Williams, Siân, additional, Yang, Xian, additional, Yeyasingham, Elizabeth, additional, Amgen, W. Yu, additional, Zetterquist, W., additional, Zolkipli, Z., additional, and Zwinderman, A.H., additional

Published
2019
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11. Efficacy of an Inhaled IL-13 Antibody Fragment in a Model of Chronic Asthma

Author

Lightwood, Daniel, primary, Tservistas, Markus, additional, Zehentleitner, Monique, additional, Sarkar, Kaushik, additional, Turner, Alison, additional, Bracher, Marguerite, additional, Smith, Bryan, additional, Lamour, Sabrina, additional, Bourne, Tim, additional, Shaw, Stevan, additional, Gozzard, Neil, additional, and Palframan, Roger T., additional

Published
2018
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13. U-BIOPRED clinical adult asthma clusters linked to a subset of sputum omics

Author

Lefaudeux, Diane, primary, De Meulder, Bertrand, additional, Loza, Matthew J., additional, Peffer, Nancy, additional, Rowe, Anthony, additional, Baribaud, Frédéric, additional, Bansal, Aruna T., additional, Lutter, Rene, additional, Sousa, Ana R., additional, Corfield, Julie, additional, Pandis, Ioannis, additional, Bakke, Per S., additional, Caruso, Massimo, additional, Chanez, Pascal, additional, Dahlén, Sven-Erik, additional, Fleming, Louise J., additional, Fowler, Stephen J., additional, Horvath, Ildiko, additional, Krug, Norbert, additional, Montuschi, Paolo, additional, Sanak, Marek, additional, Sandstrom, Thomas, additional, Shaw, Dominic E., additional, Singer, Florian, additional, Sterk, Peter J., additional, Roberts, Graham, additional, Adcock, Ian M., additional, Djukanovic, Ratko, additional, Auffray, Charles, additional, Chung, Kian Fan, additional, Adriaens, Nora, additional, Ahmed, Hassan, additional, Aliprantis, Antonios, additional, Alving, Kjell, additional, Badorek, Philipp, additional, Balgoma, David, additional, Barber, Clair, additional, Bautmans, An, additional, Behndig, Annelie F., additional, Bel, Elisabeth, additional, Beleta, Jorge, additional, Berglind, Ann, additional, Berton, Alix, additional, Bigler, Jeanette, additional, Bisgaard, Hans, additional, Bochenek, Grazyna, additional, Boedigheimer, Michael J., additional, Bøonnelykke, Klaus, additional, Brandsma, Joost, additional, Braun, Armin, additional, Brinkman, Paul, additional, Burg, Dominic, additional, Campagna, Davide, additional, Carayannopoulos, Leon, additional, Carvalho da Purfição Rocha, João P., additional, Chaiboonchoe, Amphun, additional, Chaleckis, Romanas, additional, Coleman, Courtney, additional, Compton, Chris, additional, D'Amico, Arnaldo, additional, Dahlén, Barbro, additional, De Alba, Jorge, additional, de Boer, Pim, additional, De Lepeleire, Inge, additional, Dekker, Tamara, additional, Delin, Ingrid, additional, Dennison, Patrick, additional, Dijkhuis, Annemiek, additional, Draper, Aleksandra, additional, Edwards, Jessica, additional, Emma, Rosalia, additional, Ericsson, Magnus, additional, Erpenbeck, Veit, additional, Erzen, Damijan, additional, Faulenbach, Cornelia, additional, Fichtner, Klaus, additional, Fitch, Neil, additional, Flood, Breda, additional, Frey, Urs, additional, Gahlemann, Martina, additional, Galffy, Gabriella, additional, Gallart, Hector, additional, Garret, Trevor, additional, Geiser, Thomas, additional, Gent, Jilaiha, additional, Gerhardsson de Verdier, Maria, additional, Gibeon, David, additional, Gomez, Cristina, additional, Gove, Kerry, additional, Gozzard, Neil, additional, Guo, Yi-Ke, additional, Hashimoto, Simone, additional, Haughney, John, additional, Hedlin, Gunilla, additional, Hekking, Pieter-Paul, additional, Henriksson, Elisabeth, additional, Hewitt, Lorraine, additional, Higgenbottam, Tim, additional, Hoda, Uruj, additional, Hohlfeld, Jans, additional, Holweg, Cecile, additional, Howarth, Peter, additional, Hu, Richard, additional, Hu, Sile, additional, Hu, Xugang, additional, Hudson, Val, additional, James, Anna J., additional, Kamphuis, Juliette, additional, Kennington, Erika J., additional, Kerry, Dyson, additional, Klüglich, Matthias, additional, Knobel, Hugo, additional, Knowles, Richard, additional, Knox, Alan, additional, Kolmert, Johan, additional, Konradsen, Jon, additional, Kots, Maxim, additional, Krueger, Linn, additional, Kuo, Scott, additional, Kupczyk, Maciej, additional, Lambrecht, Bart, additional, Lantz, Ann-Sofie, additional, Larsson, Lars, additional, Lazarinis, Nikos, additional, Lone-Satif, Saeeda, additional, Marouzet, Lisa, additional, Martin, Jane, additional, Masefield, Sarah, additional, Mathon, Caroline, additional, Matthews, John G., additional, Mazein, Alexander, additional, Meah, Sally, additional, Maiser, Andrea, additional, Menzies-Gow, Andrew, additional, Metcalf, Leanne, additional, Middelveld, Roelinde, additional, Mikus, Maria, additional, Miralpeix, Montse, additional, Monk, Philips, additional, Mores, Nadia, additional, Murray, Clare S., additional, Musial, Jacek, additional, Myles, David, additional, Naz, Shama, additional, Nething, Katja, additional, Nicholas, Ben, additional, Nihlen, Ulf, additional, Nilsson, Peter, additional, Nordlund, Björn, additional, Östling, Jörgen, additional, Pacino, Antonio, additional, Pahus, Laurie, additional, Palkonnen, Susanna, additional, Pavlidis, Stelios, additional, Pennazza, Giorgio, additional, Petrén, Anne, additional, Pink, Sandy, additional, Postle, Anthony, additional, Powel, Pippa, additional, Rahman-Amin, Malayka, additional, Rao, Navin, additional, Ravanetti, Lara, additional, Ray, Emma, additional, Reinke, Stacey, additional, Reynolds, Leanne, additional, Riemann, Kathrin, additional, Riley, John, additional, Robberechts, Martine, additional, Roberts, Amanda, additional, Rossios, Christos, additional, Russell, Kirsty, additional, Rutgers, Michael, additional, Santini, Giuseppe, additional, Sentoninco, Marco, additional, Schoelch, Corinna, additional, Schofield, James P.R., additional, Seibold, Wolfgang, additional, Sigmund, Ralf, additional, Sjödin, Marcus, additional, Skipp, Paul J., additional, Smids, Barbara, additional, Smith, Caroline, additional, Smith, Jessica, additional, Smith, Katherine M., additional, Söderman, Päivi, additional, Sogbesan, Adesimbo, additional, Staykova, Doroteya, additional, Strandberg, Karin, additional, Sun, Kai, additional, Supple, David, additional, Szentkereszty, Marton, additional, Tamasi, Lilla, additional, Tariq, Kamran, additional, Thörngren, John-Olof, additional, Thornton, Bob, additional, Thorsen, Jonathan, additional, Valente, Salvatore, additional, van Aalderenm, Wim, additional, van de Pol, Marianne, additional, van Drunen, Kees, additional, van Geest, Marleen, additional, Versnel, Jenny, additional, Vestbo, Jorgen, additional, Vink, Anton, additional, Vissing, Nadja, additional, von Garnier, Christophe, additional, Wagerner, Arianne, additional, Wagers, Scott, additional, Wald, Frans, additional, Walker, Samantha, additional, Ward, Jonathan, additional, Weiszhart, Zsoka, additional, Wetzel, Kristiane, additional, Wheelock, Craig E., additional, Wiegman, Coen, additional, Williams, Siân, additional, Wilson, Susan J., additional, Woosdcock, Ashley, additional, Yang, Xian, additional, Yeyashingham, Elizabeth, additional, Yu, Wen, additional, Zetterquist, Wilhelm, additional, and Zwinderman, Koos, additional

Published
2017
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15. Letters.

Author

Mardon, Chris, Harding, David, Rogers, Nick, Taylor, John, Kew, Geoff, Gozzard, Neil, Schmitt, Kass, Westmacott, Simon, Macleod, Angus M., Shiner, Mark, and Tappenden, Les

Published
2021

17. The RA-MAP Consortium: a working model for academia–industry collaboration

Author

Cope, Andrew P., Barnes, Michael R., Belson, Alexandra, Binks, Michael, Brockbank, Sarah, Bonachela-Capdevila, Francisco, Carini, Claudio, Fisher, Benjamin A., Goodyear, Carl S., Emery, Paul, Ehrenstein, Michael R., Gozzard, Neil, Harris, Ray, Hollis, Sally, Keidel, Sarah, Levesque, Marc, Lindholm, Catharina, McDermott, Michael F., McInnes, Iain B., Mela, Christopher M., Parker, Gerry, Read, Simon, Pedersen, Ayako Wakatsuki, Ponchel, Frederique, Porter, Duncan, Rao, Ravi, Rowe, Anthony, Schulze-Knappe, Peter, Sleeman, Matthew A., Symmons, Deborah, Taylor, Peter C., Tom, Brian, Tsuji, Wayne, Verbeeck, Denny, and Isaacs, John D.

Abstract

Collaboration can be challenging; nevertheless, the emerging successes of large, multi-partner, multi-national cooperatives and research networks in the biomedical sector have sustained the appetite of academics and industry partners for developing and fostering new research consortia. This model has percolated down to national funding agencies across the globe, leading to funding for projects that aim to realise the true potential of genomic medicine in the 21st century and to reap the rewards of 'big data'. In this Perspectives article, the experiences of the RA-MAP consortium, a group of more than 140 individuals affiliated with 21 academic and industry organizations that are focused on making genomic medicine in rheumatoid arthritis a reality are described. The challenges of multi-partner collaboration in the UK are highlighted and wide-ranging solutions are offered that might benefit large research consortia around the world.

Published
2018
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18. Corrigendum to “The Discovery, Engineering and Characterisation of a Highly Potent Anti-Human IL-13 Fab Fragment Designed for Administration by Inhalation” [J. Mol. Biol. 425 (2013), 577–593]

Author

Lightwood, Daniel, primary, O'Dowd, Victoria, additional, Carrington, Bruce, additional, Veverka, Vaclav, additional, Carr, Mark D., additional, Tservistas, Markus, additional, Henry, Alistair J., additional, Smith, Bryan, additional, Tyson, Kerry, additional, Lamour, Sabrina, additional, Bracher, Marguerite, additional, Sarkar, Kaushik, additional, Turner, Alison, additional, Lawson, Alastair D., additional, Bourne, Tim, additional, Gozzard, Neil, additional, and Palframan, Roger, additional

Published
2013
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19. The Discovery, Engineering and Characterisation of a Highly Potent Anti-Human IL-13 Fab Fragment Designed for Administration by Inhalation

Author

Lightwood, Daniel, primary, O'Dowd, Victoria, additional, Carrington, Bruce, additional, Veverka, Vaclav, additional, Carr, Mark D., additional, Tservistas, Markus, additional, Henry, Alistair J., additional, Smith, Bryan, additional, Tyson, Kerry, additional, Lamour, Sabrina, additional, Sarkar, Kaushik, additional, Turner, Alison, additional, Lawson, Alastair D., additional, Bourne, Tim, additional, Gozzard, Neil, additional, and Palframan, Roger, additional

Published
2013
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22. Double-stranded RNA evokes exacerbation in a mouse model of corticosteroid refractory asthma.

Author

Alba, Jorge De, Otal, Raquel, Calama, Elena, Domenech, Anna, Prats, Neus, Gozzard, Neil, and Miralpeix, Montserrat

Subjects
ANIMAL models of asthma, DOUBLE-stranded RNA, STEROID receptors, NEUTROPHILS, CHEMOKINES, ASTHMA treatment, THERAPEUTICS
Abstract

RNA viruses are a major cause of respiratory infections and are known to exacerbate asthma and other respiratory diseases. Our aim was to test the ability of poly(I:C) (polyinosinic:polycytidylic acid), a viral surrogate, to elicit exacerbation in a model of severe asthma driven by HDM (house dust mite) in FCA (Freund's complete adjuvant). Poly(I:C) was administered intranasally around the HDM challenge in FCA-HDM-sensitized animals. Changes in AHR (airway hyperresponsiveness), BALF (bronchoalveolar lavage fluid) inflammatory infiltrate, HDM-specific immunoglobulins and cytokine/chemokine release were evaluated at different points after the challenge. The effect of oral dexamethasone was also assessed. Exacerbation was achieved when poly(I:C) was administered 24 h before the HDM challenge and was characterized by enhanced AHR and an increase in the numbers of neutrophils, macrophages and lymphocytes in the BALF. Th1, Th2 and Th17 cytokines were also elevated at different time points after the challenge. Peribronchial and alveolar inflammation in lung tissue were also augmented. AHR and inflammatory infiltration showed reduced sensitivity to dexamethasone treatment. We have set up a model that mimics key aspects of viral exacerbation in a corticosteroid-refractory asthmatic phenotype which could be used to evaluate new therapies for this condition. [ABSTRACT FROM AUTHOR]

Published
2015
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23. P1-039 セルトリズマブペゴルの従来型TNF阻害薬と異なるプロファイルDifferent Profiles of Certolizumab Pegol from other TNF inhibitors

Author

Okamoto, Tadao, primary, Wada, Yumiko, additional, Bourne, Tim, additional, Fossati, Gianluca, additional, Henry, Alistair, additional, Palframan, Roger, additional, Stephens, Sue, additional, Vugler, Alexander, additional, Foulkes, Roly, additional, Gozzard, Neil, additional, Kennedy, Jeff, additional, and Nesbitt, Andrew, additional

Published
2012
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35. Corrigendum: The RA-MAP Consortium: a working model for academia–industry collaboration

Author

Cope, Andrew P., Barnes, Michael R., Belson, Alexandra, Binks, Michael, Brockbank, Sarah, Bonachela-Capdevila, Francisco, Carini, Claudio, Fisher, Benjamin A., Goodyear, Carl S., Emery, Paul, Ehrenstein, Michael R., Gozzard, Neil, Harris, Ray, Hollis, Sally, Keidel, Sarah, Levesque, Marc, Lindholm, Catharina, McDermott, Michael F., McInnes, Iain B., Mela, Christopher M., Parker, Gerry, Read, Simon, Pedersen, Ayako Wakatsuki, Ponchel, Frederique, Porter, Duncan, Rao, Ravi, Rowe, Anthony, Schulze-Knappe, Peter, Sleeman, Matthew A., Symmons, Deborah, Taylor, Peter C., Tom, Brian, Tsuji, Wayne, Verbeeck, Denny, and Isaacs, John D.

Abstract

This corrects the article DOI: 10.1038/nrrheum.2017.200

Published
2018
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37. Interferon-α-mediated therapeutic resistance in early rheumatoid arthritis implicates epigenetic reprogramming

Author

Cooles, Faye, Tarn, Jessica, Lendrem, Dennis, Naamane, Najib, Lin, Chung Ma, Millar, Ben, Maney, Nicola, Anderson, Amy, Thalayasingam, Nishanthi, Diboll, Julie, Bondet, Vincent, Duffy, Darragh, Barnes, Michael, Smith, Graham, Ng, Sandra, Watson, David, Henkin, Rafael, Cope, Andrew, Reynard, Louise, Pratt, Arthur, Isaacs, John, Newcastle University [Newcastle], Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), William Harvey Research Institute, Barts and the London Medical School, University College of London [London] (UCL), King‘s College London, RA-MAP Consortium: Adwoa Hughes-Morley, Alexandra Walker, Alexandru Cuza, Amaya Gallagher-Syed, Amy Anderson, Andrea Haynes, Andrew Filer, Andrew Long, Andrew P Cope, Angela Parke, Anthony Rowe, Arnaud Didierlaurent, Ashley Gilmour, Athula Herath, Ayako Wakatsuki, Pedersen Aysin, Tulunay Virlan, Ben Allen, Benjamin A Fisher, Blerina Kola, Bohdan Harvey, Brian Tom, Carl S Goodyear, Carolyn Cuff, Catharien Hilkens, Catharina Lindholm, Catherine T Mela, Christopher D Buckley, Chris Larminie, Chris Marshall, Christopher John, Christopher M Mela, Claudio Carini, Costantino Pitzalis, Coziana Ciurtin, Dan Baker, Daniel Ziemek, Daniela Dastros-Pitei, Dao Nguyen, David L Scott, David S Watson, Deborah Symmons, Dennis Lendrem, Denny Verbeeck, Desmond Padhji, Donna Finch, Duncan Porter, Emma Vernon, Faye Cooles, Feng Hong, Fiona Clarke, Fiona Stirling, Fowzia Ibrahim, Frances Humby, Francisco Bonachela Capdevila, Frederic Geissmann, Frederique Ponchel, Gemma Molyneux, Gemma Simpson, Georgina Thorborn, Gerry Parker, Gioia Altobelli, Graham R Smith, Hannah Edwards, Hannah Tipney, Hans-Dieter Zucht, Hayley Noble, Heidi Lempp, Humayara AliIain B McInnes, Ian C Scott, Ian N BruceIona Donnelly, Ivana Vranic, James A Butler, James Galloway, Jamie C Sergeant, Jane Worthington, Jehan El-Jawhari, Jessica Tarn, Joanne Ellis, John Casement, John Isaacs, Julie Diboll, Karim Raza, Katriona Goldmann, Kirsty Hicks, Liliane Fossati-Jimack, Lucy Rowell, Marc Levesque, Mark C Coles, Mark Coles, Mark Curran, Martin Hodge, Martin Jenkins, Mateusz Maciejewski, Matt Page, Matthew A Sleeman, Matthew J Loza, Maya Buch, Meilien Ho, Michael Binks, Michael F McDermott, Michael Macoritto, Michael R Barnes, Michael R Ehrenstein, Michele Bombardieri, Myles Lewis, Neil Gozzard, Neil Payne, Neil Ward, Nina Joseph, Paul Emery, Peter C Taylor, Peter Schulz-Knappe, Petra Budde, Philip Jones, Philip Stocks, Rachel Harry, Rafael Henkin, Ravi Rao, Ray Harris, Rekha Parmar, Ruth Toward, Sally Hollis, Samana Schwank, Samantha Lipsky, Samiul Hasan, Sandra Martins, Sandra Ng, Sarah Brockbank, Sarah Keidel, Scott Jelinsky, Sharmila Rana, Simon Read, Stephen Kelly, Stephen Wright, Steve P Young, Sukru Kaymakcalan, Susan Talbot, Suzanne Mm Verstappen, Tomi Lazarov, Tony Sabin, Valerie Ludbrook, Vernon Farewell, Wayne Tsuji, Wing Wu, Wivine Burny, Yujie Zhong, Zheng Liu, Zhilong Jia, and Vougny, Marie-Christine

Subjects
[SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, antirheumatic agents, Rheumatology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, inflammation, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, immune system diseases, Immunology, arthritis, rheumatoid, Immunology and Allergy, General Biochemistry, Genetics and Molecular Biology
Abstract

ObjectivesAn interferon (IFN) gene signature (IGS) is present in approximately 50% of early, treatment naive rheumatoid arthritis (eRA) patients where it has been shown to negatively impact initial response to treatment. We wished to validate this effect and explore potential mechanisms of action.MethodsIn a multicentre inception cohort of eRA patients (n=191), we examined the whole blood IGS (MxA, IFI44L, OAS1, IFI6, ISG15) with reference to circulating IFN proteins, clinical outcomes and epigenetic influences on circulating CD19+ B and CD4+ T lymphocytes.ResultsWe reproduced our previous findings demonstrating a raised baseline IGS. We additionally showed, for the first time, that the IGS in eRA reflects circulating IFN-α protein. Paired longitudinal analysis demonstrated a significant reduction between baseline and 6-month IGS and IFN-α levels (pPARP9, STAT1,andEPSTI1, associated with baseline IGS/IFNα levels. Differentially methylated CPG sites implicated altered transcription factor binding in B cells (GATA3, ETSI, NFATC2, EZH2) and T cells (p300, HIF1α).ConclusionsOur data suggest that, in eRA, IFN-α can cause a sustained, epigenetically mediated, pathogenic increase in lymphocyte activation and proliferation, and that the IGS is, therefore, a robust prognostic biomarker. Its persistent harmful effects provide a rationale for the initial therapeutic targeting of IFN-α in selected patients with eRA.

Published
2022

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