536 results on '"Smith, Kenneth G C"'
Search Results
2. Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19
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Hanson, Aimee L., Mulè, Matthew P., Ruffieux, Hélène, Mescia, Federica, Bergamaschi, Laura, Pelly, Victoria S., Turner, Lorinda, Kotagiri, Prasanti, Göttgens, Berthold, Hess, Christoph, Gleadall, Nicholas, Bradley, John R., Nathan, James A., Lyons, Paul A., Drakesmith, Hal, and Smith, Kenneth G. C.
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- 2024
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3. A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn's disease (PROFILE): a multicentre, open-label randomised controlled trial
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Noor, Nurulamin, Lee, James, Bond, Simon, Dowling, Francis, Brezina, Biljana, Patel, Kamal, Ahmad, Tariq, Banim, Paul, Berrill, James, Cooney, Rachel, De La Revilla Negro, Juan, de Silva, Shanika, Din, Shahida, Durai, Dharmaraj, Gordon, John, Irving, Peter, Johnson, Matthew, Kent, Alexandra, Kok, Klaartje Bel, Moran, Gordon, Mowat, Craig, Patel, Pritash, Probert, Chris, Raine, Tim, Saich, Rebecca, Seward, Abigail, Sharpstone, Dan, Smith, Melissa, Subramanian, Sreedhar, Upponi, Sara, Wiles, Alan, Williams, Horace, van Den Brink, Gijs, Vermeire, Severine, Jairath, Vipul, D'Haens, Geert, McKinney, Eoin, Lyons, Paul, Lindsay, James, Kennedy, Nicholas, Smith, Kenneth, Parkes, Miles, Allcock, Clare, Bhatti, Suhaylah, Blackwell, Jonathan, Boulton-Jones, Robert, Brookes, Matthew, Butcher, Rhys, Butterworth, Jeffrey, Champion, Karlena, Chaudhary, Rakesh, Cole, Andy, Derikx, Lauranne, Dhar, Anjan, Flowerdew, Mary, Goel, Rishi, Hart, Ailsa, Hughes, Rory, Javaid, Babur, Knight, Paul, Lee, Jacinta, Lees, Charlie, Levell, Emma, Li, Andy, Murray, Charles, O'Brien, Leisha, Parkes, Gareth, Pollok, Richard, Powles, Sam, Ramdas, Arvind, Smith, Philip, Speight, Richard Ally, Travis, Simon, Weaver, Sean, Wesley, Emma, Noor, Nurulamin M, Lee, James C, Patel, Kamal V, Banim, Paul J, Berrill, James W, Gordon, John N, Irving, Peter M, Kent, Alexandra J, Kok, Klaartje B, Moran, Gordon W, Probert, Chris S, Smith, Melissa A, Upponi, Sara S, Williams, Horace R T, van den Brink, Gijs R, Vermeire, Séverine, D'Haens, Geert R, McKinney, Eoin F, Lyons, Paul A, Lindsay, James O, Kennedy, Nicholas A, and Smith, Kenneth G C
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- 2024
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4. Employment of a high throughput functional assay to define the critical factors that influence vaccine induced cross-variant neutralizing antibodies for SARS-CoV-2
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Gu, Yue, Shunmuganathan, Bhuvaneshwari, Qian, Xinlei, Gupta, Rashi, Tan, Rebecca S. W., Kozma, Mary, Purushotorman, Kiren, Murali, Tanusya M., Tan, Nikki Y. J., Preiser, Peter R., Lescar, Julien, Nasir, Haziq, Somani, Jyoti, Tambyah, Paul A., Smith, Kenneth G. C., Renia, Laurent, Ng, Lisa F. P., Lye, David C., Young, Barnaby E., and MacAry, Paul A.
- Published
- 2023
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5. A patient-centric modeling framework captures recovery from SARS-CoV-2 infection
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Ruffieux, Hélène, Hanson, Aimee L., Lodge, Samantha, Lawler, Nathan G., Whiley, Luke, Gray, Nicola, Nolan, Tui H., Bergamaschi, Laura, Mescia, Federica, Turner, Lorinda, de Sa, Aloka, Pelly, Victoria S., Kotagiri, Prasanti, Kingston, Nathalie, Bradley, John R., Holmes, Elaine, Wist, Julien, Nicholson, Jeremy K., Lyons, Paul A., Smith, Kenneth G. C., Richardson, Sylvia, Bantug, Glenn R., and Hess, Christoph
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- 2023
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6. Homozygous IL37 mutation associated with infantile inflammatory bowel disease
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Zhang, Zinan Z., Zhang, Yu, He, Tingyan, Sweeney, Colin L., Barisc, Safa, Karakoc-Aydiner, Elif, Yao, Yikun, Ertem, Deniz, Matthews, Helen F., Gonzaga-Jauregui, Claudia, Malech, Harry L., Su, Helen C., Ozen, Ahmet, Smith, Kenneth G. C., and Lenardo, Michael J.
- Published
- 2021
7. Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity
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Meng, Bo, Abdullahi, Adam, Ferreira, Isabella A. T. M., Goonawardane, Niluka, Saito, Akatsuki, Kimura, Izumi, Yamasoba, Daichi, Gerber, Pehuén Pereyra, Fatihi, Saman, Rathore, Surabhi, Zepeda, Samantha K., Papa, Guido, Kemp, Steven A., Ikeda, Terumasa, Toyoda, Mako, Tan, Toong Seng, Kuramochi, Jin, Mitsunaga, Shigeki, Ueno, Takamasa, Shirakawa, Kotaro, Takaori-Kondo, Akifumi, Brevini, Teresa, Mallery, Donna L., Charles, Oscar J., Bowen, John E., Joshi, Anshu, Walls, Alexandra C., Jackson, Laurelle, Martin, Darren, Smith, Kenneth G. C., Bradley, John, Briggs, John A. G., Choi, Jinwook, Madissoon, Elo, Meyer, Kerstin B., Mlcochova, Petra, Ceron-Gutierrez, Lourdes, Doffinger, Rainer, Teichmann, Sarah A., Fisher, Andrew J., Pizzuto, Matteo S., de Marco, Anna, Corti, Davide, Hosmillo, Myra, Lee, Joo Hyeon, James, Leo C., Thukral, Lipi, Veesler, David, Sigal, Alex, Sampaziotis, Fotios, Goodfellow, Ian G., Matheson, Nicholas J., Sato, Kei, and Gupta, Ravindra K.
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- 2022
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8. Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies
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Collier, Dami A., De Marco, Anna, Ferreira, Isabella A. T. M., Meng, Bo, Datir, Rawlings P., Walls, Alexandra C., Kemp, Steven A., Bassi, Jessica, Pinto, Dora, Silacci-Fregni, Chiara, Bianchi, Siro, Tortorici, M. Alejandra, Bowen, John, Culap, Katja, Jaconi, Stefano, Cameroni, Elisabetta, Snell, Gyorgy, Pizzuto, Matteo S., Pellanda, Alessandra Franzetti, Garzoni, Christian, Riva, Agostino, Elmer, Anne, Kingston, Nathalie, Graves, Barbara, McCoy, Laura E., Smith, Kenneth G. C., Bradley, John R., Temperton, Nigel, Ceron-Gutierrez, Lourdes, Barcenas-Morales, Gabriela, Harvey, William, Virgin, Herbert W., Lanzavecchia, Antonio, Piccoli, Luca, Doffinger, Rainer, Wills, Mark, Veesler, David, Corti, Davide, and Gupta, Ravindra K.
- Published
- 2021
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9. SARS-CoV-2 evolution during treatment of chronic infection
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Kemp, Steven A., Collier, Dami A., Datir, Rawlings P., Ferreira, Isabella A. T. M., Gayed, Salma, Jahun, Aminu, Hosmillo, Myra, Rees-Spear, Chloe, Mlcochova, Petra, Lumb, Ines Ushiro, Roberts, David J., Chandra, Anita, Temperton, Nigel, Sharrocks, Katherine, Blane, Elizabeth, Modis, Yorgo, Leigh, Kendra E., Briggs, John A. G., van Gils, Marit J., Smith, Kenneth G. C., Bradley, John R., Smith, Chris, Doffinger, Rainer, Ceron-Gutierrez, Lourdes, Barcenas-Morales, Gabriela, Pollock, David D., Goldstein, Richard A., Smielewska, Anna, Skittrall, Jordan P., Gouliouris, Theodore, Goodfellow, Ian G., Gkrania-Klotsas, Effrossyni, Illingworth, Christopher J. R., McCoy, Laura E., and Gupta, Ravindra K.
- Published
- 2021
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10. Germline selection shapes human mitochondrial DNA diversity
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NIHR BioResource-Rare Diseases, 1001000 Genomes Project-Rare Diseases Pilot, Wei, Wei, Tuna, Salih, Keogh, Michael J., Smith, Katherine R., Aitman, Timothy J., Beales, Phil L., Bennett, David L., Gale, Daniel P., Bitner-Glindzicz, Maria A. K., Black, Graeme C., Brennan, Paul, Elliott, Perry, Flinter, Frances A., Floto, R. Andres, Houlden, Henry, Irving, Melita, Koziell, Ania, Maher, Eamonn R., Markus, Hugh S., Morrell, Nicholas W., Newman, William G., Roberts, Irene, Sayer, John A., Smith, Kenneth G. C., Taylor, Jenny C., Watkins, Hugh, Webster, Andrew R., Wilkie, Andrew O. M., Williamson, Catherine, Ashford, Sofie, Penkett, Christopher J., Stirrups, Kathleen E., Rendon, Augusto, Ouwehand, Willem H., Bradley, John R., Raymond, F. Lucy, Caulfield, Mark, Turro, Ernest, and Chinnery, Patrick F.
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- 2019
11. A CD8+ NK cell transcriptomic signature associated with clinical outcome in relapsing remitting multiple sclerosis
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McKinney, Eoin F., Cuthbertson, Iona, Harris, Kristina M., Smilek, Dawn E., Connor, Christopher, Manferrari, Giulia, Carr, Edward J., Zamvil, Scott S., and Smith, Kenneth G. C.
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- 2021
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12. Belimumab in kidney transplantation: an experimental medicine, randomised, placebo-controlled phase 2 trial
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Banham, Gemma D, Flint, Shaun M, Torpey, Nicholas, Lyons, Paul A, Shanahan, Don N, Gibson, Adele, Watson, Christopher J E, O'Sullivan, Ann-Marie, Chadwick, Joseph A, Foster, Katie E, Jones, Rachel B, Devey, Luke R, Richards, Anna, Erwig, Lars-Peter, Savage, Caroline O, Smith, Kenneth G C, Henderson, Robert B, and Clatworthy, Menna R
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- 2018
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13. Author Correction: Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies
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Collier, Dami A., De Marco, Anna, Ferreira, Isabella A. T. M., Meng, Bo, Datir, Rawlings P., Walls, Alexandra C., Kemp, Steven A., Bassi, Jessica, Pinto, Dora, Silacci-Fregni, Chiara, Bianchi, Siro, Tortorici, M. Alejandra, Bowen, John, Culap, Katja, Jaconi, Stefano, Cameroni, Elisabetta, Snell, Gyorgy, Pizzuto, Matteo S., Pellanda, Alessandra Franzetti, Garzoni, Christian, Riva, Agostino, Elmer, Anne, Kingston, Nathalie, Graves, Barbara, McCoy, Laura E., Smith, Kenneth G. C., Bradley, John R., Temperton, Nigel, Ceron-Gutierrez, Lourdes, Barcenas-Morales, Gabriela, Harvey, William, Virgin, Herbert W., Lanzavecchia, Antonio, Piccoli, Luca, Doffinger, Rainer, Wills, Mark, Veesler, David, Corti, Davide, and Gupta, Ravindra K.
- Published
- 2022
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14. Author Correction: SARS-CoV-2 evolution during treatment of chronic infection
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Kemp, Steven A., Collier, Dami A., Datir, Rawlings P., Ferreira, Isabella A. T. M., Gayed, Salma, Jahun, Aminu, Hosmillo, Myra, Rees-Spear, Chloe, Mlcochova, Petra, Lumb, Ines Ushiro, Roberts, David J., Chandra, Anita, Temperton, Nigel, Sharrocks, Katherine, Blane, Elizabeth, Modis, Yorgo, Leigh, Kendra E., Briggs, John A. G., van Gils, Marit J., Smith, Kenneth G. C., Bradley, John R., Smith, Chris, Doffinger, Rainer, Ceron-Gutierrez, Lourdes, Barcenas-Morales, Gabriela, Pollock, David D., Goldstein, Richard A., Smielewska, Anna, Skittrall, Jordan P., Gouliouris, Theodore, Goodfellow, Ian G., Gkrania-Klotsas, Effrossyni, Illingworth, Christopher J. R., McCoy, Laura E., and Gupta, Ravindra K.
- Published
- 2022
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15. Proinflammatory cytokines driving cardiotoxicity in Covid-19
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Colzani, Maria, primary, Bargehr, Johannes, additional, Mescia, Federica, additional, Williams, Eleanor C, additional, Knight-Schrijver, Vincent, additional, Lee, Jonathan, additional, Summers, Charlotte, additional, Mohorianu, Irina, additional, Smith, Kenneth G C, additional, Lyons, Paul A, additional, and Sinha, Sanjay, additional
- Published
- 2023
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16. Genetic feature engineering enables characterisation of shared risk factors in immune-mediated diseases
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Burren, Oliver S., Reales, Guillermo, Wong, Limy, Bowes, John, Lee, James C., Barton, Anne, Lyons, Paul A., Smith, Kenneth G. C., Thomson, Wendy, Kirk, Paul D. W., and Wallace, Chris
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- 2020
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17. Author Correction: Ultrasensitive amplicon barcoding for next-generation sequencing facilitating sequence error and amplification-bias correction
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Ahmed, Ibrahim, Tucci, Felicia A., Aflalo, Aure, Smith, Kenneth G. C., and Bashford-Rogers, Rachael J. M.
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- 2020
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18. Ultrasensitive amplicon barcoding for next-generation sequencing facilitating sequence error and amplification-bias correction
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Ahmed, Ibrahim, Tucci, Felicia A., Aflalo, Aure, Smith, Kenneth G. C., and Bashford-Rogers, Rachael J. M.
- Published
- 2020
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19. Systemic Lupus Erythematosus
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Nijjar, Jagtar Singh, primary and Smith, Kenneth G C, additional
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- 2020
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20. List of Contributors
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Abramson, Jakub, primary, Ahmed, S. Sohail, additional, Alba, Marco A., additional, Ali, Youssif M., additional, Ambrus, Julian L., additional, Andersson Svärd, Agnes, additional, Aringer, Martin, additional, Assassi, Shervin, additional, Aung, Thanda, additional, Ayzenberg, Ilya, additional, Barker, Robert N., additional, Baxter, Alan G., additional, Betterle, Corrado, additional, Birlea, Stanca A., additional, Björkström, Niklas K., additional, Blair, Paul A., additional, Blüml, Stephan, additional, Bosch, Xavier, additional, Brodsky, Robert A., additional, Bryceson, Yenan T., additional, Burkett, Patrick R., additional, Bussel, James B., additional, Caricchio, Roberto, additional, Casciola-Rosen, Livia, additional, Caturegli, Patrizio, additional, Chaigne-Delalande, Benjamin, additional, Chalan, Paulina, additional, Chatenoud, Lucienne, additional, Cohen, Philip L., additional, Cooper, Megan A., additional, Coppieters, Ken, additional, Crystal, Ronald G., additional, Culton, Donna A., additional, Damato, Valentina, additional, Davidson, Anne, additional, Delfino, Lorenzo, additional, Delves, Peter J., additional, Di Dalmazi, Giulia, additional, Diamond, Betty, additional, Diaz, Luis A., additional, Falk, Ronald J., additional, Fritzler, Marvin J., additional, Gallucci, Stefania, additional, Gangaputra, Sapna, additional, Gelbman, Brian, additional, Gershwin, M. Eric, additional, Gery, Igal, additional, Getts, Daniel R., additional, Gold, Ralf, additional, Goldfarb, Yael, additional, Gong, Jing, additional, Gordon, Siamon, additional, Goronzy, Jörg J., additional, Greer, Judith M., additional, Guazzone, Vanesa A., additional, Guilherme, Luiza, additional, Hafler, David A., additional, Hahn, Bevra H., additional, Hamad, Abdel Rahim A., additional, Hamano, Hideaki, additional, Harrison, Leonard C., additional, Homann, Dirk, additional, Husebye, Eystein S., additional, Jennette, J. Charles, additional, Jones, Richard J., additional, Jordan, Margaret A., additional, Kalil, Jorge, additional, Kawa, Shigeyuki, additional, Kaya, Ziya, additional, Keller, Christian W., additional, King, Nicholas J.C., additional, Kitcharoensakkul, Maleewan, additional, Kiyosawa, Kendo, additional, Königs, Christoph, additional, Kronenberg, Mitchell, additional, Kuchroo, Vijay K., additional, Laurence, Arian, additional, Lee, Eun-Ju, additional, Lehmann, Helmar C., additional, Lernmark, Åke, additional, Lindbladh, Ida, additional, Liu, Zhi, additional, Ljunggren, Hans-Gustaf, additional, Lunardi, Claudio, additional, Lundin, Knut E.A., additional, Lünemann, Jan D., additional, Lunn, Michael P.T., additional, Lustig, Livia, additional, Mackay, Charles R., additional, Mackay, Ian R., additional, Malattia, Clara, additional, Martinez-Pomares, Luisa, additional, Martini, Alberto, additional, Mauri, Claudia, additional, McCombe, Pamela A., additional, Melchers, Fritz, additional, Mieli-Vergani, Giorgina, additional, Miller, Frederick W., additional, Miller, Stephen D., additional, Mizui, Masayuki, additional, Mjösberg, Jenny, additional, Münz, Christian, additional, Nijjar, Jagtar Singh, additional, Norris, David A., additional, Oleinika, Kristine, additional, Oppenheim, Joost J., additional, Pawlak, Mathias, additional, Peligero-Cruz, Cristina, additional, Peters, Anneli, additional, Peterson, Pärt, additional, Pitarokoili, Kalliopi, additional, Presotto, Fabio, additional, Puccetti, Antonio, additional, Rabb, Hamid, additional, Raczek, Patricia, additional, Rahman, M. Jubayer, additional, Ramos-Casals, Manuel, additional, Rose, Noel R., additional, Rosen, Antony, additional, Sadasivam, Mohanraj, additional, Schiffenbauer, Adam, additional, Schwaeble, Wilhelm J., additional, Sen, H. Nida, additional, Serota, Marc, additional, Sheikh, Kazim A., additional, Shoenfeld, Yehuda, additional, Shovman, Ora, additional, Sieper, Joachim, additional, Silverstein, Arthur M., additional, Sim, Robert B., additional, Smith, Kenneth G C, additional, Smolen, Josef S., additional, Sollid, Ludvig M., additional, Spiteri, Alanna, additional, Steinman, Lawrence, additional, Stone, John H., additional, Syrbe, Uta, additional, Tamhaney, Ami, additional, Tanaka, Atsushi, additional, Taneja, Veena, additional, Tarbell, Kristin V., additional, Tinazzi, Elisa, additional, Tiong, Benedict K., additional, Toh, Ban-Hock, additional, Tsokos, George C., additional, Tung, Kenneth S.K., additional, Varga, John, additional, Vergani, Diego, additional, Vickers, Mark A., additional, Viegas, Stuart, additional, Vincent, Angela, additional, von Herrath, Matthias, additional, Weetman, Anthony P., additional, Weinstock, Joel V., additional, Wentworth, John M., additional, Wesley, Sarah, additional, Weyand, Cornelia M., additional, Wingender, Gerhard, additional, Winter, Michael W., additional, Zanchetta, Renato, additional, and Zouali, Moncef, additional
- Published
- 2020
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21. Reduced circulating BMP9 and pBMP10 in hospitalized COVID-19 patients
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Dunmore, Benjamin J, Upton, Paul D, Auckland, Kate, Samanta, Romit J, Lyons, Paul A, Smith, Kenneth G C, Gräf, Stefan, Summers, Charlotte, Morrell, Nicholas W, Smith, Kenneth G C [0000-0003-3829-4326], and Apollo - University of Cambridge Repository
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Endothelial Cell Dysfunction ,Bmps ,Viral Infections And Pathogenesis - Abstract
Similar to other causes of acute respiratory distress syndrome, coronavirus disease 2019 (COVID-19) is characterized by the aberrant expression of vascular injury biomarkers. We present the first report that circulating plasma bone morphogenetic proteins (BMPs), BMP9 and pBMP10, involved in vascular protection, are reduced in hospitalized patients with COVID-19.
- Published
- 2023
22. FcγRIIb differentially regulates pre-immune and germinal center B cell tolerance in mouse and human
- Author
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Espéli, Marion, Bashford-Rogers, Rachael, Sowerby, John M., Alouche, Nagham, Wong, Limy, Denton, Alice E., Linterman, Michelle A., and Smith, Kenneth G. C.
- Published
- 2019
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23. Proinflammatory cytokines driving cardiotoxicity in COVID-19.
- Author
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Colzani, Maria, Bargehr, Johannes, Mescia, Federica, Williams, Eleanor C, Knight-Schrijver, Vincent, Lee, Jonathan, Summers, Charlotte, Mohorianu, Irina, Smith, Kenneth G C, Lyons, Paul A, and Sinha, Sanjay
- Subjects
COVID-19 pandemic ,HUMAN embryonic stem cells ,CARDIOTOXICITY ,COVID-19 ,ADULT respiratory distress syndrome - Abstract
Aims Cardiac involvement is common in patients hospitalized with COVID-19 and correlates with an adverse disease trajectory. While cardiac injury has been attributed to direct viral cytotoxicity, serum-induced cardiotoxicity secondary to serological hyperinflammation constitutes a potentially amenable mechanism that remains largely unexplored. Methods and results To investigate serological drivers of cardiotoxicity in COVID-19 we have established a robust bioassay that assessed the effects of serum from COVID-19 confirmed patients on human embryonic stem cell (hESC)-derived cardiomyocytes. We demonstrate that serum from COVID-19 positive patients significantly reduced cardiomyocyte viability independent of viral transduction, an effect that was also seen in non-COVID-19 acute respiratory distress syndrome (ARDS). Serum from patients with greater disease severity led to worse cardiomyocyte viability and this significantly correlated with levels of key inflammatory cytokines, including IL-6, TNF-α, IL1-β, IL-10, CRP, and neutrophil to lymphocyte ratio with a specific reduction of CD4
+ and CD8+ cells. Combinatorial blockade of IL-6 and TNF-α partly rescued the phenotype and preserved cardiomyocyte viability and function. Bulk RNA sequencing of serum-treated cardiomyocytes elucidated specific pathways involved in the COVID-19 response impacting cardiomyocyte viability, structure, and function. The observed effects of serum-induced cytotoxicity were cell-type selective as serum exposure did not adversely affect microvascular endothelial cell viability but resulted in endothelial activation and a procoagulant state. Conclusion These results provide direct evidence that inflammatory cytokines are at least in part responsible for the cardiovascular damage seen in COVID-19 and characterise the downstream activated pathways in human cardiomyocytes. The serum signature of patients with severe disease indicates possible targets for therapeutic intervention. [ABSTRACT FROM AUTHOR]- Published
- 2024
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24. Obesity Is Associated with Attenuated Tissue Immunity in COVID-19
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Guo, Shuang A., primary, Bowyer, Georgina S., additional, Ferdinand, John R., additional, Maes, Mailis, additional, Tuong, Zewen K., additional, Gillman, Eleanor, additional, Liao, Mingfeng, additional, Lindeboom, Rik G. H., additional, Yoshida, Masahiro, additional, Worlock, Kaylee, additional, Gopee, Hudaa, additional, Stephenson, Emily, additional, Gao, Catherine A., additional, Lyons, Paul A., additional, Smith, Kenneth G. C., additional, Haniffa, Muzlifah, additional, Meyer, Kerstin B., additional, Nikolić, Marko Z., additional, Zhang, Zheng, additional, Wunderink, Richard G., additional, Misharin, Alexander V., additional, Dougan, Gordon, additional, Navapurkar, Vilas, additional, Teichmann, Sarah A., additional, Conway Morris, Andrew, additional, and Clatworthy, Menna R., additional
- Published
- 2023
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25. Prevalence of CFTR variants in PID patients with bronchiectasis - an important modifying co-factor
- Author
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Lawless, Dylan, primary, Allen, Hana Lango, additional, Thaventhiran, James E.D., additional, Goddard, Sarah, additional, Burren, Oliver S., additional, Robson, Evie, additional, Peckham, Daniel, additional, Smith, Kenneth G C, additional, and Savic, Sinisa, additional
- Published
- 2023
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26. Sec22b is a critical and nonredundant regulator of plasma cell maintenance
- Author
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Bonaud, Amélie, primary, Gargowitsch, Laetitia, additional, Gilbert, Simon M., additional, Rajan, Elanchezhian, additional, Canales-Herrerias, Pablo, additional, Stockholm, Daniel, additional, Rahman, Nabila F., additional, Collins, Mark O., additional, Taskiran, Hakan, additional, Hill, Danika L., additional, Alloatti, Andres, additional, Alouche, Nagham, additional, Balor, Stéphanie, additional, Soldan, Vanessa, additional, Gillet, Daniel, additional, Barbier, Julien, additional, Bachelerie, Françoise, additional, Smith, Kenneth G. C., additional, Jellusova, Julia, additional, Bruhns, Pierre, additional, Amigorena, Sebastian, additional, Balabanian, Karl, additional, Linterman, Michelle A., additional, Peden, Andrew A., additional, and Espéli, Marion, additional
- Published
- 2023
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27. FcγRIIb inhibits immune complex-induced VEGF-A production and intranodal lymphangiogenesis
- Author
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Clatworthy, Menna R., Harford, Sarah K., Mathews, Rebeccah J., and Smith, Kenneth G. C.
- Published
- 2014
28. Genome-wide association study identifies distinct genetic contributions to prognosis and susceptibility in Crohn's disease
- Author
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Lee, James C, Biasci, Daniele, Roberts, Rebecca, Gearry, Richard B, Mansfield, John C, Ahmad, Tariq, Prescott, Natalie J, Satsangi, Jack, Wilson, David C, Jostins, Luke, Anderson, Carl A, Traherne, James A, Lyons, Paul A, Parkes, Miles, and Smith, Kenneth G C
- Published
- 2017
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29. Single-cell multi-omics analysis of the immune response in COVID-19
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Stephenson, Emily, Reynolds, Gary, Botting, Rachel A., Calero-Nieto, Fernando J., Morgan, Michael D., Tuong, Zewen Kelvin, Bach, Karsten, Sungnak, Waradon, Worlock, Kaylee B., Yoshida, Masahiro, Kumasaka, Natsuhiko, Kania, Katarzyna, Engelbert, Justin, Olabi, Bayanne, Spegarova, Jarmila Stremenova, Wilson, Nicola K., Mende, Nicole, Jardine, Laura, Gardner, Louis C. S., Goh, Issac, Horsfall, Dave, McGrath, Jim, Webb, Simone, Mather, Michael W., Lindeboom, Rik G. H., Dann, Emma, Huang, Ni, Polanski, Krzysztof, Prigmore, Elena, Gothe, Florian, Scott, Jonathan, Payne, Rebecca P., Baker, Kenneth F., Hanrath, Aidan T., Schim van der Loeff, Ina C. D., Barr, Andrew S., Sanchez-Gonzalez, Amada, Bergamaschi, Laura, Mescia, Federica, Barnes, Josephine L., Kilich, Eliz, de Wilton, Angus, Saigal, Anita, Saleh, Aarash, Janes, Sam M., Smith, Claire M., Gopee, Nusayhah, Wilson, Caroline, Coupland, Paul, Coxhead, Jonathan M., Kiselev, Vladimir Yu, van Dongen, Stijn, Bacardit, Jaume, King, Hamish W., Rostron, Anthony J., Simpson, A. John, Hambleton, Sophie, Laurenti, Elisa, Lyons, Paul A., Meyer, Kerstin B., Nikolić, Marko Z., Duncan, Christopher J. A., Smith, Kenneth G. C., Teichmann, Sarah A., Clatworthy, Menna R., Marioni, John C., Göttgens, Berthold, and Haniffa, Muzlifah
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Proteome ,COVID-19 ,Cross-Sectional Studies ,Humans ,Monocytes ,Receptors, Antigen, B-Cell ,Receptors, Antigen, T-Cell ,SARS-CoV-2 ,Single-Cell Analysis ,T-Lymphocytes ,Transcriptome ,CD34 ,Biology ,Peripheral blood mononuclear cell ,Article ,General Biochemistry, Genetics and Molecular Biology ,Immune system ,Antigen ,Receptors ,Platelet activation ,Progenitor cell ,B-Cell ,RNA sequencing ,General Medicine ,T-Cell ,Haematopoiesis ,Viral infection ,Immunology ,Infection ,CD8 - Abstract
Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy., Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.
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- 2021
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30. GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements
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Dixon, Peter H., Levine, Adam P., Cebola, Inês, Chan, Melanie M. Y., Amin, Aliya S., Aich, Anshul, Mozere, Monika, Maude, Hannah, Mitchell, Alice L., Zhang, Jun, Adlard, Julian, Ahmed, Munaza, Aitman, Tim, Alachkar, Hana, Allsup, David, Almeida-King, Jeff, Ancliff, Philip, Antrobus, Richard, Armstrong, Ruth, Arno, Gavin, Ashford, Sofie, Astle, William, Attwood, Anthony, Babbs, Chris, Bakchoul, Tamam, Bariana, Tadbir, Barwell, Julian, Bennett, David, Bentley, David, Bierzynska, Agnieszka, Biss, Tina, Bleda, Marta, Bogaard, Harm, Bourne, Christian, Boyce, Sara, Bradley, John, Breen, Gerome, Brennan, Paul, Brewer, Carole, Brown, Matthew, Browning, Michael, Buchan, Rachel, Buckland, Matthew, Bueser, Teofila, Burns, Siobhan, Burren, Oliver, Calleja, Paul, Carr-White, Gerald, Carss, Keren, Casey, Ruth, Caulfield, Mark, Chambers, John, Chambers, Jennifer, Cheng, Floria, Chinnery, Patrick F., Christian, Martin, Church, Colin, Brod, Naomi Clements, Coghlan, Gerry, Colby, Elizabeth, Cole, Trevor, Collins, Janine, Collins, Peter, Colombo, Camilla, Condliffe, Robin, Cook, Stuart, Cook, Terry, Cooper, Nichola, Corris, Paul, Crisp-Hihn, Abigail, Curry, Nicola, Danesino, Cesare, Daniels, Matthew, Daugherty, Louise, Davis, John, Deevi, Sri V. V., Dent, Timothy, Dewhurst, Eleanor, Dixon, Peter, Downes, Kate, Drazyk, Anna, Drewe, Elizabeth, Dutt, Tina, Edgar, David, Edwards, Karen, Egner, William, Erber, Wendy, Erwood, Marie, Estiu, Maria C., Evans, Gillian, Evans, Dafydd Gareth, Everington, Tamara, Eyries, Mélanie, Favier, Remi, Fletcher, Debra, Fox, James, Frary, Amy, French, Courtney, Freson, Kathleen, Frontini, Mattia, Gale, Daniel, Gall, Henning, Geoghegan, Claire, Gerighty, Terry, Ghio, Stefano, Ghofrani, Hossein-Ardeschir, Gibbs, Simon, Gilmour, Kimberley, Girerd, Barbara, Goddard, Sarah, Gomez, Keith, Gordins, Pavels, Gosal, David, Gräf, Stefan, Grassi, Luigi, Greene, Daniel, Greenhalgh, Lynn, Greinacher, Andreas, Gresele, Paolo, Griffiths, Philip, Grigoriadou, Sofia, Grocock, Russell, Grozeva, Detelina, Hackett, Scott, Hadinnapola, Charaka, Hague, William, Haimel, Matthias, Hall, Matthew, Hanson, Helen, Harkness, Kirsty, Harper, Andrew, Harris, Claire, Hart, Daniel, Hassan, Ahamad, Hayman, Grant, Henderson, Alex, Hoffmann, Jonathan, Horvath, Rita, Houweling, Arjan, Howard, Luke, Hu, Fengyuan, Hudson, Gavin, Hughes, Joseph, Huissoon, Aarnoud, Humbert, Marc, Humphray, Sean, Hunter, Sarah, Hurles, Matthew, Izatt, Louise, James, Roger, Johnson, Sally, Jolles, Stephen, Jolley, Jennifer, Jurkute, Neringa, Kasanicki, Mary, Kazkaz, Hanadi, Kazmi, Rashid, Kelleher, Peter, Kiely, David, Kingston, Nathalie, Klima, Robert, Kostadima, Myrto, Kovacs, Gabor, Koziell, Ania, Kreuzhuber, Roman, Kuijpers, Taco, Kumar, Ajith, Kumararatne, Dinakantha, Kuria, Manju, Laffa, Michael, Lalloo, Fiona, Lamber, Michele, Alle, Hana Lango, Lawrie, Allan, Layton, Mark, Lentaigne, Claire, Levine, Adam, Linger, Rachel, Longhurst, Hilary, Louka, Eleni, Ross, Robert MacKenzie, Madan, Bella, Maher, Eamonn, Maimaris, Jesmeen, Mangles, Sarah, Mapeta, Rutendo, Marchbank, Kevin, Marks, Stephen, Markus, Hugh S., Marshall, Andrew, Martin, Jennifer, Mathias, Mary, Matthews, Emma, Maxwell, Heather, McAlinden, Paul, McCarthy, Mark, Meacham, Stuart, Mead, Adam, Megy, Karyn, Mehta, Sarju, Michaelides, Michel, Millar, Carolyn, Moledina, Shahin, Montani, David, Moor, Tony, Morrell, Nicholas, Muir, Keith, Mumford, Andrew, Newnham, Michael, O'Sullivan, Jennifer, Obaji, Samya, Okoli, Steven, Olschewski, Andrea, Olschewski, Horst, Ong, Kai Ren, Ormondroy, Elizabeth, Ouwehan, Willem, Papadi, Sofia, Park, Soo-Mi, Parry, David, Paterson, Joan, Peacock, Andrew, Peden, John, Peerlinck, Kathelijne, Penkett, Christopher, Pepke-Zaba, Joanna, Petersen, Romina, Pyle, Angela, Rankin, Stuart, Rao, Anupama, Raymond, F. Lucy, Rayner-Matthew, Paula, Rees, Christine, Rendon, Augusto, Renton, Tara, Rice, Andrew, Richardson, Sylvia, Richter, Alex, Roberts, Irene, Roughley, Catherine, Roy, Noemi, Sadeghi-Alavijeh, Omid, Saleem, Moin, Samani, Nilesh, Sanchis-Juan, Alba, Sargur, Ravishankar, Satchell, Simon, Savic, Sinisa, Scelsi, Laura, Schulman, Sol, Scully, Marie, Searle, Claire, Seeger, Werner, Sewell, Carrock, Seyres, Denis, Shapiro, Susie, Sharmardina, Olga, Shtoyerman, Rakefet, Sibson, Keith, Side, Lucy, Simeoni, Ilenia, Simpson, Michael, Sivapalaratnam, Suthesh, Skytte, Anne-Bine, Smith, Katherine, Smith, Kenneth G. C., Snape, Katie, Soubrier, Florent, Staines, Simon, Staples, Emily, Stark, Hannah, Stephens, Jonathan, Stirrups, Kathleen, Stock, Sophie, Suntharalingam, Jay, Swietlik, Emilia, Tait, R. Campbell, Talks, Kate, Tan, Rhea, Thaventhiran, James, Themistocleous, Andreas, Thomas, Moira, Thomson, Kate, Thrasher, Adrian, Thys, Chantal, Tischkowitz, Marc, Titterton, Catherine, Toh, Cheng-Hock, Toshner, Mark, Traylor, Matthew, Treacy, Carmen, Trembath, Richard, Tuna, Salih, Turek, Wojciech, Turro, Ernest, Vale, Tom, Van Geet, Chris, Van Zuydam, Natalie, Vazquez-Lopez, Marta, von Ziegenweidt, Julie, Noordegraaf, Anton Vonk, Waisfisz, Quintin, Walker, Suellen, Ware, James, Watkins, Hugh, Watt, Christopher, Webster, Andrew, Wei, Wei, Welch, Steven, Wessels, Julie, Westbury, Sarah, Westwood, John-Paul, Wharton, John, Whitehorn, Deborah, Whitworth, James, Wilkins, Martin R., Wong, Edwin, Wood, Nicholas, Wood, Yvette, Woods, Geoff, Woodward, Emma, Wort, Stephen, Worth, Austen, Yates, Katherine, Yong, Patrick, Young, Tim, Yu, Ping, Yu-Wai-Man, Patrick, Ambrose, J. C., Arumugam, P., Bevers, R., Bleda, M., Boardman-Pretty, F., Boustred, C. R., Brittain, H., Brown, M. A., Caulfield, M. J., Chan, G. C., Fowler, T., Giess, A., Hamblin, A., Henderson, S., Hubbard, T. J. P., Jackson, R., Jones, L. J., Kasperaviciute, D., Kayikci, M., Kousathanas, A., Lahnstein, L., Leigh, S. E. A., Leong, I. U. S., Lopez, F. J., Maleady-Crowe, F., McEntagart, M., Minneci, F., Moutsianas, L., Mueller, M., Murugaesu, N., Need, A. C., O'Donovan, P., Odhams, C. A., Patch, C., Perez-Gil, D., Pereira, M. B., Pullinger, J., Rahim, T., Rendon, A., Rogers, T., Savage, K., Sawant, K., Scott, R. H., Siddiq, A., Sieghart, A., Smith, S. C., Sosinsky, A., Stuckey, A., Tanguy, M., Taylor Tavares, A. L., Thomas, E. R. A., Thompson, S. R., Tucci, A., Welland, M. J., Williams, E., Witkowska, K., Wood, S. M., Chambers, Jenny, Syngelaki, Argyro, Donnelly, Jennifer, Cooley, Sharon, Geary, Michael, Nicolaides, Kypros, Thorsell, Malin, Hague, William M., Estiu, Maria Cecilia, Marschall, Hanns-Ulrich, Gale, Daniel P., Williamson, Catherine, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Human genetics, ACS - Atherosclerosis & ischemic syndromes, Pediatrics, Foundation for the National Institutes of Health (FNIH), The Academy of Medical Sciences, British Heart Foundation, Imperial College Healthcare NHS Trust- BRC Funding, Paediatric Infectious Diseases / Rheumatology / Immunology, and ARD - Amsterdam Reproduction and Development
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VARIANT ,LOCI ,INTEGRATIVE ANALYSIS ,General Physics and Astronomy ,Cholestasis, Intrahepatic ,TRIGLYCERIDE LEVELS ,DISEASE ,General Biochemistry, Genetics and Molecular Biology ,Bile Acids and Salts ,Pregnancy ,Humans ,MUTATION ,Science & Technology ,Multidisciplinary ,Genomics England Research Consortium Collaborators ,Infant, Newborn ,NIHR BioResource ,General Chemistry ,GLUCOCORTICOID-RECEPTOR ,Multidisciplinary Sciences ,ALKALINE SPHINGOMYELINASE ,Pregnancy Complications ,INSIGHTS ,Science & Technology - Other Topics ,Premature Birth ,Female ,FASTING GLUCOSE ,Genome-Wide Association Study - Abstract
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5-2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility. ispartof: NATURE COMMUNICATIONS vol:13 issue:1 ispartof: location:England status: published
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- 2022
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31. Magnetic resonance imaging with hyperpolarized [1,4-¹³C₂]fumarate allows detection of early renal acute tubular necrosis
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Clatworthy, Menna R., Kettunen, Mikko I., De-En Hu, Mathews, Rebeccah J., Witney, Timothy H., Kennedy, Brett W. C., Bohndiek, Sarah E., Gallagher, Ferdia A., Jarvis, Lorna, Smith, Kenneth G. C., and Brindle, Kevin M.
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- 2012
32. Spontaneous, persistent T-cell dependent IFN-γ release in patients who progress to Long COVID
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Krishna, Benjamin A., primary, Lim, Eleanor Y., additional, Mactavous, Lenette, additional, Jackson, Sarah, additional, Team, NIHR BioResource, additional, Lyons, Paul A., additional, Doffinger, Rainer, additional, Bradley, John R., additional, Smith, Kenneth G. C., additional, Sinclair, John, additional, Matheson, Nicholas J., additional, Lehner, Paul J., additional, Sithole, Nyaradzai, additional, and Wills, Mark R., additional
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- 2022
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33. Immunodeficiency, autoimmunity, and increased risk of B cell malignancy in humans with TRAF3 mutations
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Rae, William, primary, Sowerby, John M., additional, Verhoeven, Dorit, additional, Youssef, Mariam, additional, Kotagiri, Prasanti, additional, Savinykh, Natalia, additional, Coomber, Eve L., additional, Boneparth, Alexis, additional, Chan, Angela, additional, Gong, Chun, additional, Jansen, Machiel H., additional, du Long, Romy, additional, Santilli, Giorgia, additional, Simeoni, Ilenia, additional, Stephens, Jonathan, additional, Wu, Kejia, additional, Zinicola, Marta, additional, Allen, Hana Lango, additional, Baxendale, Helen, additional, Kumararatne, Dinakantha, additional, Gkrania-Klotsas, Effrossyni, additional, Scheffler Mendoza, Selma C., additional, Yamazaki-Nakashimada, Marco Antonio, additional, Ruiz, Laura Berrón, additional, Rojas-Maruri, Cesar Mauricio, additional, Lugo Reyes, Saul O., additional, Lyons, Paul A., additional, Williams, Anthony P., additional, Hodson, Daniel J., additional, Bishop, Gail A., additional, Thrasher, Adrian J., additional, Thomas, David C., additional, Murphy, Michael P., additional, Vyse, Timothy J., additional, Milner, Joshua D., additional, Kuijpers, Taco W., additional, and Smith, Kenneth G. C., additional
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- 2022
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34. Genetic susceptibility to systemic lupus erythematosus protects against cerebral malaria in mice
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Waisberg, Michael, Tarasenko, Tatyana, Vickers, Brandi K., Scott, Bethany L., Willcocks, Lisa C., Molina-Cruz, Alvaro, Pierce, Matthew A., Huang, Chiung-yu, Torres-Velez, Fernando J., Smith, Kenneth G. C., Barillas-Mury, Carolina, Miller, Louis H., Pierce, Susan K., and Bolland, Silvia
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- 2011
35. Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2
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Collier, Dami A., Ferreira, Isabella A. T. M., Kotagiri, Prasanti, Datir, Rawlings P., Lim, Eleanor Y., Touizer, Emma, Meng, Bo, Abdullahi, Adam, Elmer, Anne, Kingston, Nathalie, Graves, Barbara, Le Gresley, Emma, Caputo, Daniela, Bergamaschi, Laura, Smith, Kenneth G. C., Bradley, John R., Ceron-Gutierrez, Lourdes, Cortes-Acevedo, Paulina, Barcenas-Morales, Gabriela, Linterman, Michelle A., McCoy, Laura E., Davis, Chris, Thomson, Emma, McKinney, Eoin, Doffinger, Rainer, Wills, Mark, Gupta, Ravindra K., Baker, Stephen, Dougan, Gordon, Hess, Christoph, Lehner, Paul J., Lyons, Paul A., Matheson, Nicholas J., Owehand, Willem H., Saunders, Caroline, Summers, Charlotte, Thaventhiran, James E. D., Toshner, Mark, Weekes, Michael P., Maxwell, Patrick, Shaw, Ashley, Bucke, Ashlea, Calder, Jo, Canna, Laura, Domingo, Jason, Fuller, Stewart, Harris, Julie, Hewitt, Sarah, Kennet, Jane, Jose, Sherly, Kourampa, Jenny, Meadows, Anne, O’Brien, Criona, Price, Jane, Publico, Cherry, Rastall, Rebecca, Ribeiro, Carla, Rowlands, Jane, Ruffolo, Valentina, Tordesillas, Hugo, Bullman, Ben, Dunmore, Benjamin J., Fawke, Stuart, Gräf, Stefan, Hodgson, Josh, Huang, Christopher, Hunter, Kelvin, Jones, Emma, Legchenko, Ekaterina, Matara, Cecilia, Martin, Jennifer, Mescia, Federica, O’Donnell, Ciara, Pointon, Linda, Pond, Nicole, Shih, Joy, Sutcliffe, Rachel, Tilly, Tobias, Treacy, Carmen, Tong, Zhen, Wood, Jennifer, Wylot, Marta, Betancourt, Ariana, Bower, Georgie, Cossetti, Chiara, De Sa, Aloka, Epping, Madeline, Gleadall, Nick, Grenfell, Richard, Hinch, Andrew, Huhn, Oisin, Jackson, Sarah, Jarvis, Isobel, Krishna, Ben, Lewis, Daniel, Marsden, Joe, Nice, Francesca, Okecha, Georgina, Omarjee, Ommar, Perera, Marianne, Potts, Martin, Richoz, Nathan, Romashova, Veronika, Yarkoni, Natalia Savinykh, Sharma, Rahul, Stefanucci, Luca, Stephens, Jonathan, Strezlecki, Mateusz, Turner, Lori, D. D. De Bie, Eckart M., Bunclark, Katherine, Josipovic, Masa, Mackay, Michael, Michael, Alice, Rossi, Sabrina, Selvan, Mayurun, Spencer, Sarah, Yong, Cissy, Ansaripour, Ali, Mwaura, Lucy, Patterson, Caroline, Polwarth, Gary, Polgarova, Petra, Di Stefano, Giovanni, Fahey, Codie, Michel, Rachel, Bong, Sze-How, Coudert, Jerome D., Holmes, Elaine, Allison, John, Butcher, Helen, Clapham-Riley, Debbie, Dewhurst, Eleanor, Furlong, Anita, Gray, Jennifer, Ivers, Tasmin, Kasanicki, Mary, Linger, Rachel, Meloy, Sarah, Muldoon, Francesca, Ovington, Nigel, Papadia, Sofia, Phelan, Isabel, Stark, Hannah, Stirrups, Kathleen E., Townsend, Paul, Walker, Neil, Webster, Jennifer, Collier, Dami A. [0000-0001-5446-4423], Datir, Rawlings P. [0000-0003-0521-2144], Smith, Kenneth G. C. [0000-0003-3829-4326], Linterman, Michelle A. [0000-0001-6047-1996], McCoy, Laura E. [0000-0001-9503-7946], Thomson, Emma [0000-0003-1482-0889], Lyons, Paul A. [0000-0001-7035-8997], Gupta, Ravindra K. [0000-0001-9751-1808], and Apollo - University of Cambridge Repository
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article ,13/106 ,38/39 ,631/250/2152/2153/1291 ,631/326/596/4130 ,38 - Abstract
Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating.
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- 2021
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36. Sex-specific association of X-linked Toll-like receptor 7 (TLR7) with male systemic lupus erythematosus
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Shen, Nan, Fu, Qiong, Deng, Yun, Qian, Xiaoxia, Zhao, Jian, Kaufman, Kenneth M., Wu, Yee Ling, Yu, C. Yung, Tang, Yuanjia, Chen, Ji-Yih, Yang, Wanling, Wong, Maida, Kawasaki, Aya, Tsuchiya, Naoyuki, Sumida, Takayuki, Kawaguchi, Yasushi, Howe, Hwee Siew, Mok, Mo Yin, Bang, So-Young, Liu, Fei-Lan, Chang, Deh-Ming, Takasaki, Yoshinari, Hashimoto, Hiroshi, Harley, John B., Guthridge, Joel M., Grossman, Jennifer M., Cantor, Rita M., Song, Yeong Wook, Bae, Sang-Cheol, Chen, Shunle, Hahn, Bevra H., Lau, Yu Lung, Tsao, Betty P., and Smith, Kenneth G. C.
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- 2010
37. A defunctioning polymorphism in FCGR2B is associated with protection against malaria but susceptibility to systemic lupus erythematosus
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Willcocks, Lisa C., Carr, Edward J., Niederer, Heather A., Rayner, Tim F., Williams, Thomas N., Yang, Wanling, Scott, J. Anthony G., Urban, Britta C., Peshu, Norbert, Vyse, Timothy J., Lau, Yu Lung, Lyons, Paul A., Smith, Kenneth G. C., and Fearon, Douglas T.
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- 2010
38. Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts tropism and fusogenicity
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80728270, Meng, Bo, Abdullahi, Adam, Ferreira, Isabella A. T. M., Goonawardane, Niluka, Saito, Akatsuki, Kimura, Izumi, Yamasoba, Daichi, Gerber, Pehuén Pereyra, Fatihi, Saman, Rathore, Surabhi, Zepeda, Samantha K., Papa, Guido, Kemp, Steven A., Ikeda, Terumasa, Toyoda, Mako, Tan, Toong Seng, Kuramochi, Jin, Mitsunaga, Shigeki, Ueno, Takamasa, Shirakawa, Kotaro, Takaori-Kondo, Akifumi, Brevini, Teresa, Mallery, Donna L., Charles, Oscar J., The CITIID-NIHR BioResource COVID-19 Collaboration, The Genotype to Phenotype Japan (G2P-Japan) Consortium, Ecuador-COVID19 Consortium, Bowen, John E., Joshi, Anshu, Walls, Alexandra C., Jackson, Laurelle, Martin, Darren, Smith, Kenneth G. C., Bradley, John, Briggs, John A. G., Choi, Jinwook, Madissoon, Elo, Meyer, Kerstin, Mlcochova, Petra, Ceron-Gutierrez, Lourdes, Doffinger, Rainer, Teichmann, Sarah A., Fisher, Andrew J., Pizzuto, Matteo S., de Marco, Anna, Corti, Davide, Hosmillo, Myra, Lee, Joo Hyeon, James, Leo C., Thukral, Lipi, Veesler, David, Sigal, Alex, Sampaziotis, Fotios, Goodfellow, Ian G., Matheson, Nicholas J., Sato, Kei, Gupta, Ravindra K., 80728270, Meng, Bo, Abdullahi, Adam, Ferreira, Isabella A. T. M., Goonawardane, Niluka, Saito, Akatsuki, Kimura, Izumi, Yamasoba, Daichi, Gerber, Pehuén Pereyra, Fatihi, Saman, Rathore, Surabhi, Zepeda, Samantha K., Papa, Guido, Kemp, Steven A., Ikeda, Terumasa, Toyoda, Mako, Tan, Toong Seng, Kuramochi, Jin, Mitsunaga, Shigeki, Ueno, Takamasa, Shirakawa, Kotaro, Takaori-Kondo, Akifumi, Brevini, Teresa, Mallery, Donna L., Charles, Oscar J., The CITIID-NIHR BioResource COVID-19 Collaboration, The Genotype to Phenotype Japan (G2P-Japan) Consortium, Ecuador-COVID19 Consortium, Bowen, John E., Joshi, Anshu, Walls, Alexandra C., Jackson, Laurelle, Martin, Darren, Smith, Kenneth G. C., Bradley, John, Briggs, John A. G., Choi, Jinwook, Madissoon, Elo, Meyer, Kerstin, Mlcochova, Petra, Ceron-Gutierrez, Lourdes, Doffinger, Rainer, Teichmann, Sarah A., Fisher, Andrew J., Pizzuto, Matteo S., de Marco, Anna, Corti, Davide, Hosmillo, Myra, Lee, Joo Hyeon, James, Leo C., Thukral, Lipi, Veesler, David, Sigal, Alex, Sampaziotis, Fotios, Goodfellow, Ian G., Matheson, Nicholas J., Sato, Kei, and Gupta, Ravindra K.
- Abstract
The SARS-CoV-2 Omicron BA.1 variant emerged in 20211 and bears multiple spike mutations2. Here we show that Omicron spike has higher affinity for ACE2 compared to Delta as well as a marked change of antigenicity conferring significant evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralising antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralisation. Importantly, antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lower airway organoids, lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared to Delta. Replication differences mapped to entry efficiency using spike pseudotyped virus (PV) assays. The defect for Omicron PV to enter specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and knock down of TMPRSS2 impacted Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways3 demonstrated that the Omicron spike inefficiently utilises the cellular protease TMPRSS2 that promotes cell entry via plasma membrane fusion, with greater dependency on cell entry via the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to utilise TMPRSS2, syncytium formation by the Omicron spike was markedly impaired compared to the Delta spike. Omicron’s less efficient spike cleavage at S1/S2 is associated with shift in cellular tropism away from TMPRSS2 expressing cells, with implications for altered pathogenesis.
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- 2022
39. Longitudinal multi-omics analysis identifies early blood-based predictors of anti-TNF therapy response in inflammatory bowel disease
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Mishra, Neha, Aden, Konrad, Sørensen, Signe B, Overgaard, Silja H, Schulte, Berenice, Nikolaus, Susanna, Rey, Guillaume, Gasparoni, Gilles, Lyons, Paul A, Schultze, Joachim L, Walter, Jörn, Andersen, Vibeke, Blase, Johanna I, Consortium, SYSCID, Dermitzakis, Emmanouil T, Schreiber, Stefan, Rosenstiel, Philip, Banos, Aggelos, Bertsias, George, Beyer, Marc-Daniel, Boumpas, Dimitrios, Finckh, Axel, Franke, Andre, Baran, Nathan, Georges, Michel, Gu, Wei, Häsler, Robert, Jawhara, Mohamad, Kenyon, Amy, Kratsch, Christina, Krause, Roland, Lauc, Gordan, Mangino, Massimo, Natoli, Gioacchino, Bordoni, Dora, Ostaszewski, Marek, Pezer, Marija, Raes, Jeroen, Rahmouni, Souad, Ramos-Pamplona, Marilou, Reiz, Benedikt, Rosati, Elisa, Sanoudou, Despina, Satagopam, Venkata, Schneider, Reinhard, Tran, Florian, Schulte-Schrepping, Jonas, Sidiropoulos, Prodromos, Smith, Kenneth G C, Spector, Timothy, Vandeputte, Doris, Vieira-Silva, Sara, Vojta, Aleksandar, Warnat-Herresthal, Stefanie, Zoldoš, Vlatka, Conrad, Claudio, Avalos, Diana, Jaeckel, Charlot, and Scherer, Michael
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Tumor Necrosis Factor-alpha ,genetics [Inflammatory Bowel Diseases] ,Intestinal inflammation ,Therapy response ,Biomarker ,Biologics ,Inflammatory Bowel Diseases ,Personalized medicine ,Infliximab ,drug therapy [Inflammatory Bowel Diseases] ,therapeutic use [Interferons] ,Genetics ,therapeutic use [Infliximab] ,Molecular Medicine ,Humans ,RNA ,Tumor Necrosis Factor Inhibitors ,ddc:610 ,Prospective Studies ,Interferons ,Molecular Biology ,Genetics (clinical) ,Biomarkers - Abstract
Background and aims Treatment with tumor necrosis factor α (TNFα) antagonists in IBD patients suffers from primary non-response rates of up to 40%. Biomarkers for early prediction of therapy success are missing. We investigated the dynamics of gene expression and DNA methylation in blood samples of IBD patients treated with the TNF antagonist infliximab and analyzed the predictive potential regarding therapy outcome. Methods We performed a longitudinal, blood-based multi-omics study in two prospective IBD patient cohorts receiving first-time infliximab therapy (discovery: 14 patients, replication: 23 patients). Samples were collected at up to 7 time points (from baseline to 14 weeks after therapy induction). RNA-sequencing and genome-wide DNA methylation data were analyzed and correlated with clinical remission at week 14 as a primary endpoint. Results We found no consistent ex ante predictive signature across the two cohorts. Longitudinally upregulated transcripts in the non-remitter group comprised TH2- and eosinophil-related genes including ALOX15, FCER1A, and OLIG2. Network construction identified transcript modules that were coherently expressed at baseline and in non-remitting patients but were disrupted at early time points in remitting patients. These modules reflected processes such as interferon signaling, erythropoiesis, and platelet aggregation. DNA methylation analysis identified remission-specific temporal changes, which partially overlapped with transcriptomic signals. Machine learning approaches identified features from differentially expressed genes cis-linked to DNA methylation changes at week 2 as a robust predictor of therapy outcome at week 14, which was validated in a publicly available dataset of 20 infliximab-treated CD patients. Conclusions Integrative multi-omics analysis reveals early shifts of gene expression and DNA methylation as predictors for efficient response to anti-TNF treatment. Lack of such signatures might be used to identify patients with IBD unlikely to benefit from TNF antagonists at an early time point.
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- 2022
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40. Dendritic Cell Stimulation by Mycobacterial Hsp70 Is Mediated through CCR5
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Floto, R. Andres, MacAry, Paul A., Boname, Jessica M., Mien, Tan Suet, Kampmann, Beate, Hair, James R., Huey, Oh Seen, Houben, Edith N. G., Pieters, Jean, Day, Cheryl, Oehlmann, Wulf, Singh, Mahavir, Smith, Kenneth G. C., and Lehner, Paul J.
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- 2006
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41. Immune complexes stimulate CCR7-dependent dendritic cell migration to lymph nodes
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Clatworthy, Menna R, Aronin, Caren E Petrie, Mathews, Rebeccah J, Morgan, Nicole Y, Smith, Kenneth G C, and Germain, Ronald N
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- 2014
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42. The immunopathology of ANCA-associated vasculitis
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McKinney, Eoin F., Willcocks, Lisa C., Broecker, Verena, and Smith, Kenneth G. C.
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- 2014
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43. Plasma cell maintenance and antibody secretion are under the control of Sec22b-mediated regulation of organelle dynamics
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Bonaud, Amelie, primary, Gargowitsch, Laetitia, additional, Gilbert, Simon, additional, Rajan, Elanchezhian, additional, Canales-Herrerias, Pablo, additional, Stockholm, Daniel, additional, Rahman, Nabila, additional, Collins, Mark, additional, Hill, Danika L, additional, Alloatti, Andres, additional, Alouche, Nagham, additional, Balor, Stephanie, additional, Soldan, Vanessa, additional, Gillet, Daniel, additional, Barbier, Julien, additional, Bachelerie, Francoise, additional, Smith, Kenneth G. C., additional, Bruhns, Pierre, additional, Amigorena, Sebastian, additional, Balabanian, Karl, additional, Linterman, Michelle A, additional, Peden, Andrew, additional, and Espeli, Marion, additional
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- 2022
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44. MT-HESS: an efficient Bayesian approach for simultaneous association detection in OMICS datasets, with application to eQTL mapping in multiple tissues
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Lewin, Alex, Saadi, Habib, Peters, James E., Moreno-Moral, Aida, Lee, James C., Smith, Kenneth G. C., Petretto, Enrico, Bottolo, Leonardo, and Richardson, Sylvia
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- 2016
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45. FcγRIIB and autoimmunity
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Espéli, Marion, Smith, Kenneth G. C., and Clatworthy, Menna R.
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- 2016
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46. T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection
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McKinney, Eoin F., Lee, James C., Jayne, David R. W., Lyons, Paul A., and Smith, Kenneth G. C.
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- 2015
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47. Long-term follow-up of patients who received repeat-dose rituximab as maintenance therapy for ANCA-associated vasculitis
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Alberici, Federico, Smith, Rona M., Jones, Rachel B., Roberts, Darren M., Willcocks, Lisa C., Chaudhry, Afzal, Smith, Kenneth G. C., and Jayne, David R. W.
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- 2015
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48. Reduced circulating BMP9 and pBMP10 in hospitalized COVID‐19 patients.
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Dunmore, Benjamin J., Upton, Paul D., Auckland, Kate, Samanta, Romit J., Lyons, Paul A., Smith, Kenneth G. C., Gräf, Stefan, Summers, Charlotte, and Morrell, Nicholas W.
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COVID-19 ,BONE morphogenetic proteins ,HOSPITAL patients ,ADULT respiratory distress syndrome - Abstract
Similar to other causes of acute respiratory distress syndrome, coronavirus disease 2019 (COVID‐19) is characterized by the aberrant expression of vascular injury biomarkers. We present the first report that circulating plasma bone morphogenetic proteins (BMPs), BMP9 and pBMP10, involved in vascular protection, are reduced in hospitalized patients with COVID‐19. [ABSTRACT FROM AUTHOR]
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- 2023
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49. FcγRIIB in autoimmunity and infection: evolutionary and therapeutic implications
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Smith, Kenneth G. C. and Clatworthy, Menna R.
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- 2010
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50. EROS is a selective chaperone regulating the phagocyte NADPH oxidase and purinergic signalling
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Randzavola, Lyra O., primary, Mortimer, Paige M., additional, Garside, Emma, additional, Dufficy, Elizabeth R., additional, Schejtman, Andrea, additional, Roumelioti, Georgia, additional, Yu, Lu, additional, Pardo, Mercedes, additional, Spirohn, Kerstin, additional, Tolley, Charlotte, additional, Brandt, Cordelia, additional, Harcourt, Katherine, additional, Nichols, Esme, additional, Nahorski, Mike, additional, Woods, Geoff, additional, Williamson, James C., additional, Suresh, Shreehari, additional, Sowerby, John M., additional, Matsumoto, Misaki, additional, Santos, Celio X.C., additional, Kiar, Cher Shen, additional, Mukhopadhyay, Subhankar, additional, Rae, Will M., additional, Dougan, Gordon J., additional, Grainger, John, additional, Lehner, Paul J., additional, Calderwood, Michael, additional, Choudhary, Jyoti, additional, Clare, Simon, additional, Speak, Anneliese, additional, Santilli, Giorgia, additional, Bateman, Alex, additional, Smith, Kenneth G. C., additional, Magnani, Francesca, additional, and Thomas, David C., additional
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- 2021
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