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1. The efficacy and safety of systemic corticosteroids as first line treatment for granulomatous lymphocytic interstitial lung disease

Author

Smits, Bas, Goldacker, Sigune, Seneviratne, Suranjith, Malphettes, Marion, Longhurst, Hilary, Mohamed, Omar E., Witt-Rautenberg, Carla, Leeman, Lucy, Schwaneck, Eva, Raymond, Isabelle, Meghit, Kilifa, Uhlmann, Annette, Winterhalter, Christine, van Montfrans, Joris, Klima, Marion, Workman, Sarita, Fieschi, Claire, Lorenzo, Lorena, Boyle, Sonja, Onyango-Odera, Shamin, Price, Suzanne, Schmalzing, Marc, Aurillac, Valerie, Prasse, Antje, Hartmann, Ieneke, Meerburg, Jennifer J., Kemner-van de Corput, Mariette, Tiddens, Harm, Grimbacher, Bodo, Kelleher, Peter, Patel, Smita Y., Korganow, Anne-Sophie, Viallard, Jean-Francois, Tony, Hans-Peter, Bethune, Claire, Schulze-Koops, Hendrik, Witte, Torsten, Huissoon, Aarnoud, Baxendale, Helen, Grigoriadou, Sofia, Oksenhendler, Eric, Burns, Siobhan O., and Warnatz, Klaus

Published
2023
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2. SARS-CoV-2 Vaccine Responses in Individuals with Antibody Deficiency: Findings from the COV-AD Study

Author

Shields, Adrian M., Faustini, Sian E., Hill, Harriet J., Al-Taei, Saly, Tanner, Chloe, Ashford, Fiona, Workman, Sarita, Moreira, Fernando, Verma, Nisha, Wagg, Hollie, Heritage, Gail, Campton, Naomi, Stamataki, Zania, Klenerman, Paul, Thaventhiran, James E. D., Goddard, Sarah, Johnston, Sarah, Huissoon, Aarnoud, Bethune, Claire, Elcombe, Suzanne, Lowe, David M., Patel, Smita Y., Savic, Sinisa, Burns, Siobhan O., and Richter, Alex G.

Published
2022
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5. Case report: Clearance of longstanding, immune-deficiency-associated, vaccine-derived polio virus infection following remdesivir therapy for chronic SARS-CoV-2 infection

Author

William Hywel Bermingham, Benjamin Canning, Thomas Wilton, Michael Kidd, Dimitra Klapsa, Manasi Majumdar, Kavitha Sooriyakumar, Javier Martin, and Aarnoud P. Huissoon

Subjects
polio, vaccine derived poliovirus, immune deficiency associated vaccine derived poliovirus (iVDPV), remdesivir, CVID - common variable immunodeficiency disorders, primary immune deficiencies (PID), Immunologic diseases. Allergy, RC581-607
Abstract

The global polio eradication campaign has had remarkable success in reducing wild-type poliovirus infection, largely built upon the live attenuated Sabin oral poliovirus vaccine. Whilst rare, vaccine poliovirus strains may cause infection and subsequently revert to a neurovirulent type, termed vaccine-derived poliovirus (VDPV). Persistent, vaccine derived infection may occur in an immunocompromised host (iVDPV), where it is a recognised complication following receipt of the Sabin vaccine. This has significant implications for the global polio eradication campaign and there is currently no agreed global strategy to manage such patients.Here we describe a case of a 50-year-old man with common variable immune deficiency, persistently infected with a neurovirulent vaccine-derived type 2 poliovirus following vaccination in childhood. iVDPV infection had proven resistant to multiple prior attempts at treatment with human breast milk, ribavirin and oral administration of a normal human pooled immunoglobulin product. His iVDPV infection subsequently resolved after 12 days treatment with remdesivir, an adenosine analogue prodrug that is an inhibitor of viral RNA-dependent RNA polymerase, administered as treatment for a prolonged, moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. iVDPV from the patient, isolated prior to treatment, was subsequently demonstrated to be sensitive to remdesivir in vitro. Based on the observations made in this case, and the mechanistic rationale for use with iVDPV, there is strong justification for further clinical studies of remdesivir treatment as a potentially curative intervention in patients with iVDPV infection.

Published
2023
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6. Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations

Author

Boztug, Kaan, Brunner, Juergen, Demel, Ulrike F., Förster-Waldl, Elisabeth, Gasteiger, Lukas M., Göschl, Lisa, Kojić, Marina, Schroll, Andrea, Seidel, Markus G., Wintergerst, Uwe, Wisgrill, Lukas, Sharapova, Svetlana O., Goffard, Jean-Christophe, Kerre, Tessa, Meyts, Isabelle, Roosens, Fine, Smet, Julie, Haerynck, Filomeen, Eric, Zelimir Pavle, Milenova, Veneta, Gagro, Alenka, Richter, Darko, Chovancova, Zita, Hlavackova, Eva, Litzman, Jiri, Milota, Tomas, Sediva, Anna, Elaziz, Dalia Abd, Alkady, Radwa Salaheldin, El Sayed El Hawary, Rabab, Eldash, Alia S., Galal, Nermeen, Lotfy, Sohilla, Meshaal, Safa S., Reda, Shereen M., Sobh, Ali, Elmarsafy, Aisha, Seppänen, Mikko R.J., Brosselin, Pauline, Courteille, Virginie, De Vergnes, Nathalie, Kracker, Sven, Pergent, Martine, Randrianomenjanahary, Philippe, Ahrenstorf, Gerrit, Albert, Michael H., Ankermann, Tobias, Atschekzei, Faranaz, Baumann, Ulrich, Becker, Benjamin C., Behrends, Uta, Belohradsky, Bernd H., Biegner, Anika-Kerstin, Binder, Nadine, Bode, Sebastian F.N., Boesecke, Christoph, Boetticher, Benedikt, Borte, Michael, Borte, Stephan, Classen, Carl Friedrich, Dirks, Johannes, Dückers, Gregor, El-Helou, Sabine, Ernst, Diana, Fasshauer, Maria, Fecker, Gisela, Felgentreff, Kerstin, Foell, Dirk, Ghosh, Sujal, Girschick, Hermann J., Goldacker, Sigune, Graf, Norbert, Graf, Dagmar, Greil, Johann, Hanitsch, Leif Gunnar, Hauck, Fabian, Heeg, Maximilian, Heine, Sabine I., Henes, Joerg C., Hoenig, Manfred, Holzer, Ursula, Holzinger, Dirk, Horneff, Gerd, Hundsdoerfer, Patrick, Jablonka, Alexandra, Jakoby, Donate, Joean, Oana, Kaiser-Labusch, Petra, Klemann, Christian, Kobbe, Robin, Körholz, Julia, Kramm, Christof M., Krüger, Renate, Landwehr-Kenzel, Sybille, Lehmberg, Kai, Liese, Johannes G., Lippert, Conrad Ferdinand, Maccari, Maria Elena, Masjosthusmann, Katja, Meinhardt, Andrea, Metzler, Markus, Morbach, Henner, Müller, Ingo, Naumann-Bartsch, Nora, Neubert, Jennifer, Niehues, Tim, Peter, Hans-Hartmut, Rieber, Nikolaus, Ritterbusch, Henrike, Rockstroh, Jürgen Kurt, Roesler, Joachim, Schauer, Uwe, Scheible, Raphael, Schmalzing, Marc, Schmidt, Reinhold Ernst, Schneider, Dominik T., Schreiber, Stefan, Schuetz, Catharina, Schulz, Ansgar, Schulze-Koops, Hendrik, Schulze-Sturm, Ulf, Schuster, Volker, Schwaneck, Eva C., Schwarz, Klaus, Schwarze-Zander, Carolynne, Sirin, Mehtap, Skapenko, Alla, Sogkas, Georgios, Sparber-Sauer, Monika, Speckmann, Carsten, Steinmann, Sandra, Stiehler, Sophie, Tenbrock, Klaus, von Bernuth, Horst, Warnatz, Klaus, Wasmuth, Jan-Christian, Weiss, Michael, Witte, Torsten, Wittke, Kirsten, Wittkowski, Helmut, Zeuner, Rainald A., Farmaki, Evangelia, Hatzistilianou, Maria N., Kakkas, Ioannis, Kanariou, Maria G., Kapousouzi, Androniki, Liatsis, Emmanouil, Maggina, Paraskevi, Papadopoulou-Alataki, Efimia, Raptaki, Maria, Speletas, Matthaios, Tantou, Sofia, Goda, Vera, Kriván, Gergely, Marodi, Laszlo, Abolhassani, Hassan, Aghamohammadi, Asghar, Rezaei, Nima, Feighery, Conleth, Leahy, Timothy Ronan, Ryan, Paul, Batzir, Nurit Assia, Garty, Ben Zion, Tamary, Hannah, Aiuti, Alessandro, Amodio, Donato, Azzari, Chiara, Barzaghi, Federica, Baselli, Lucia A., Cancrini, Caterina, Carrabba, Maria, Cazzaniga, Marco, Cesaro, Simone, Chinello, Matteo, Danieli, Maria Giovanna, Dellepiane, Rosa Maria, Fabio, Giovanna, Gambineri, Eleonora, Lodi, Lorenzo, Lougaris, Vassilios, Marasco, Carolina, Martire, Baldassarre, Marzollo, Antonio, Milito, Cinzia, Moschese, Viviana, Pignata, Claudio, Plebani, Alessandro, Porta, Fulvio, Quinti, Isabella, Ricci, Silvia, Soresina, Annarosa, Tommasini, Alberto, Vacca, Angelo, Vanessa, Clementina, Blažienė, Audra, Sitkauskiene, Brigita, Gowin, Ewelina, Heropolitańska-Pliszka, Edyta, Pietrucha, Barbara, Szaflarska, Anna, Więsik-Szewczyk, Ewa, Wolska-Kuśnierz, Beata, Esteves, Isabel, Faria, Emilia, Marques, Laura Hora, Neves, João Farela, Silva, Susana L., Teixeira, Carla, Pereira da Silva, Sara, Capilna, Brindusa Ruxandra, Guseva, Marina N., Shcherbina, Anna, Bobcakova, Anna, Ciznar, Peter, Gabzdilova, Juliana, Jesenak, Milos, Kapustova, Lenka, Orosova, Jaroslava, Petrovicova, Otilia, Raffac, Stefan, Kopač, Peter, Allende, Luis M., Antolí, Arnau, Blanch, Gemma Rocamora, Carbone, Javier, Dieli-Crimi, Romina, Garcia-Prat, Marina, Gil-Herrera, Juana, Gonzalez-Granado, Luis Ignacio, Agulló, Pilar Llobet, Olbrich, Peter, Parra-Martínez, Alba, Paz-Artal, Estela, Pleguezuelo, Daniel E., Rodríguez, Nerea Salmón, Sánchez-Ramón, Silvia, Santos-Pérez, Juan Luis, Solanich, Xavier, Soler-Palacin, Pere, González-Amores, Miriam, Ekwall, Olov, Fasth, Anders, Bitzenhofer-Grüber, Michaela, Candotti, Fabio, Dimitriou, Florentia, Heininger, Ulrich, Holbro, Andreas, Jandus, Peter, Kolios, Antonios G.A., Marschall, Karin, Schmid, Jana Pachlopnik, Posfay-Barbe, Klara M., Prader, Seraina, Reichenbach, Janine, Steiner, Urs C., Trück, Johannes, Bredius, Robbert G., de Kruijf- Bazen, Suzanne, de Vries, Esther, Henriet, Stefanie S.V., Kuijpers, Taco W., Potjewijd, Judith, Rutgers, Abraham, Stol, Kim, van Aerde, Koen J., Van den Berg, J. Merlijn, van de Ven, Annick A.J.M., Montfrans, Jorisvan, Aydemir, Sezin, Baris, Safa, Dogu, Figen, Ikinciogullari, Aydan, Karakoc-Aydiner, Elif, Kilic, Sara S., Kiykim, Ayca, Kökçü Karadağ, Şefika İlknur, Kutukculer, Necil, Ocak, Suheyla, UNAL, Ekrem, Boyarchuk, Oksana, Hilfanova, Anna, Kostyuchenko, Larysa V., Alachkar, Hana, Arkwright, Peter D., Baxendale, Helen E., Bernatoniene, Jolanta, Coulter, Tanya I., Garcez, Tomaz, Goddard, Sarah, Gompels, Mark M., Grigoriadou, Sofia, Herriot, Richard, Herwadkar, Archana, Huissoon, Aarnoud, Ibberson, Lisa, Nademi, Zoreh, Noorani, Sadia, Parvin, Shahnaz, Steele, Cathal Laurence, Thomas, Moira, Waruiru, Catherine, Yong, Patrick F.K., Bourne, Helen, Thalhammer, Julian, Kindle, Gerhard, Nieters, Alexandra, Rusch, Stephan, Fischer, Alain, Grimbacher, Bodo, Edgar, David, Buckland, Matthew, Mahlaoui, Nizar, and Ehl, Stephan

Published
2021
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9. COVID-19 in patients with primary and secondary immunodeficiency: The United Kingdom experience

Author

Anantharachagan, Ariharan, Arumugakani, Gururaj, Baker, Kenneth, Bahal, Sameer, Bermingham, William, Bhole, Malini, Boules, Evon, Bright, Philip, Burns, Siobhan, Cleave, Betsy, Dempster, John, Devlin, Lisa, Dhalla, Fatima, Drewe, Elizabeth, Duncan, Christopher, Dziadzio, Magdalena, Elkhalifa, Shuayb, Gennery, Andrew, Goddard, Sarah, Grigoriadou, Sofia, Hayman, Grant, Herwadkar, Archana, Huissoon, Aarnoud, Jain, Rashmi, Jolles, Stephen, Johnston, Sarah, Leeman, Lucy, Mahabir, Shanti, MacLochlainn, Dylan, McDermott, Elizabeth, Misbah, Siraj, Morsi, Hadeil, Murng, Sai, Noorani, Sadia, O’Brien, Rachael, Patel, Smita, Price, Arthur, Richter, Alex, Savic, Sinisa, Seneviratne, Suranjith, Shields, Adrian, Shrimpton, Anna, Stroud, Catherine, Vaitla, Prashantha, Verma, Nisha, Shields, Adrian M., Burns, Siobhan O., and Richter, Alex G.

Published
2021
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10. Impact of vaccination on hospitalization and mortality from COVID-19 in patients with primary and secondary immunodeficiency: The United Kingdom experience

Author

Adrian M. Shields, Susan Tadros, Adam Al-Hakim, Jeremy M. Nell, Me Me Nay Lin, Michele Chan, Sarah Goddard, John Dempster, Magdalena Dziadzio, Smita Y. Patel, Shuayb Elkalifa, Aarnoud Huissoon, Christopher J. A. Duncan, Archana Herwadkar, Sujoy Khan, Claire Bethune, Suzanne Elcombe, James Thaventhiran, Paul Klenerman, David M. Lowe, Sinisa Savic, Siobhan O. Burns, and Alex G. Richter

Subjects
COVID-19, CVID, inborn errors of immunity, primary immunodeficiency, secondary immunodeficiency, vaccination, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundIndividuals with primary and secondary immunodeficiency (PID/SID) were shown to be at risk of poor outcomes during the early stages of the SARS-CoV-2 pandemic. SARS-CoV-2 vaccines demonstrate reduced immunogenicity in these patients.ObjectivesTo understand whether the risk of severe COVID-19 in individuals with PID or SID has changed following the deployment of vaccination and therapeutics in the context of the emergence of novel viral variants of concern.MethodsThe outcomes of two cohorts of patients with PID and SID were compared: the first, infected between March and July 2020, prior to vaccination and treatments, the second after these intervention became available between January 2021 and April 2022.Results22.7% of immunodeficient patients have been infected at least once with SARS-CoV-2 since the start of the pandemic, compared to over 70% of the general population. Immunodeficient patients were typically infected later in the pandemic when the B.1.1.529 (Omicron) variant was dominant. This delay was associated with receipt of more vaccine doses and higher pre-infection seroprevalence. Compared to March-July 2020, hospitalization rates (53.3% vs 17.9%, p

Published
2022
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12. Increased Seroprevalence and Improved Antibody Responses Following Third Primary SARS-CoV-2 Immunisation: An Update From the COV-AD Study

Author

Adrian M. Shields, Sian E. Faustini, Harriet J. Hill, Saly Al-Taei, Chloe Tanner, Fiona Ashford, Sarita Workman, Fernando Moreira, Nisha Verma, Hollie Wagg, Gail Heritage, Naomi Campton, Zania Stamataki, Mark T. Drayson, Paul Klenerman, James E. D. Thaventhiran, Shuayb Elkhalifa, Sarah Goddard, Sarah Johnston, Aarnoud Huissoon, Claire Bethune, Suzanne Elcombe, David M. Lowe, Smita Y. Patel, Sinisa Savic, Alex G. Richter, Siobhan O. Burns, the COV-AD consortium, Zahra Ahmed, Angus Best, Joanne Dasgin, Mohammad Dinally, Elena Efstathiou, Theresa McCarthy, Madeeha Hoque, Shannon Page, Timothy Plant, Zehra Suleiman, Neil Townsend, Charlotte Trinham, Sinead Walder, Hollie Bancroft, Michelle Bates, Hayley Clifford, Christopher McGee, Samuel Chee, Lucy Common, Archana Herwadkar, Karen Knowles, Maria Poulaka, Georgina Davis, Daniel Mullan, Stuart Wareham, Fatima Dhalla, Rashmi Jain, Hadeil Morsi, Nicholas Peters, Mark Gompels, Malgorzata Slowinsksa, Dan Hartland, Emily Heritage, Joe Humphreys, Deborah Hughes, Ann Ivory, Sinead Kelly, Eileen O’Grady, and Archana Shajidevadas

Subjects
COVID-19, CVID, inborn errors of immunity, primary immunodeficiency, secondary immunodeficiency, vaccination, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundPatients with primary and secondary antibody deficiency are vulnerable to COVID-19 and demonstrate diminished responses following two-dose SARS-CoV-2 vaccine schedules. Third primary vaccinations have been deployed to enhance their humoral and cellular immunity.ObjectivesTo determine the immunogenicity of the third primary SARS-CoV-2 immunisation in a heterogeneous cohort of patients with antibody deficiency.MethodsParticipants enrolled in the COV-AD study were sampled before and after their third vaccine dose. Serological and cellular responses were determined using ELISA, live-virus neutralisation and ELISPOT assays.ResultsFollowing a two-dose schedule, 100% of healthy controls mounted a serological response to SARS-CoV-2 vaccination, however, 38.6% of individuals with antibody deficiency remained seronegative. A third primary SARS-CoV-2 vaccine significantly increased anti-spike glycoprotein antibody seroprevalence from 61.4% to 76.0%, the magnitude of the antibody response, its neutralising capacity and induced seroconversion in individuals who were seronegative after two vaccine doses. Vaccine-induced serological responses were broadly cross-reactive against the SARS-CoV-2 B.1.1.529 variant of concern, however, seroprevalence and antibody levels remained significantly lower than healthy controls. No differences in serological responses were observed between individuals who received AstraZeneca ChAdOx1 nCoV-19 and Pfizer BioNTech 162b2 during their initial two-dose vaccine schedule. SARS-CoV-2 infection-naive participants who had received a heterologous vaccine as a third dose were significantly more likely to have a detectable T cell response following their third vaccine dose (61.5% vs 11.1%).ConclusionThese data support the widespread use of third primary immunisations to enhance humoral immunity against SARS-CoV-2 in individuals with antibody deficiency.

Published
2022
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14. Characterization of the clinical and immunologic phenotype and management of 157 individuals with 56 distinct heterozygous NFKB1 mutations

Author

Adhya, Zoe, Alachkar, Hana, Anantharachagan, Ariharan, Antrobus, Richard, Arumugakani, Gururaj, Ashford, Sofie, Astle, William J., Attwood, Anthony, Bacchelli, Chiara, Batista, Joana, Baxendale, Helen E., Bethune, Claire, Bibi, Shahnaz, Bleda, Marta, Boardman, Barbara, Booth, Claire, Bradley, John R., Breen, Gerome, Brown, Matthew, Browning, Michael J., Brownlie, Mary, Buckland, Matthew S., Burns, Siobhan O., Burren, Oliver S., Carss, Keren, Chambers, John, Chandra, Anita, Brod, Naomi Clements, Clifford, Hayley, Cooper, Nichola, Daugherty, Louise C., Davies, E.G., Davies, Sophie, Davis, John, Deacock, Sarah, Deevi, Sri V.V., Dempster, John, Devlin, Lisa A., Dewhurst, Eleanor F., Downes, Kate, Drewe, Elizabeth, Duarte, Daniel, Edgar, J. David M., Edwards, Karen, Egner, William, El-Shanawany, Tariq, Erwood, Marie, Fletcher, Debra, Fox, James, Frary, Amy J., Frontini, Mattia, Furnell, Abigail, Gaspar, H. Bobby, Ghurye, Rohit, Gilmour, Kimberly C., Gleadall, Nicholas S., Goddard, Sarah, Gordins, Pavels, Gräf, Stefan, Grassi, Luigi, Greene, Daniel, Grigoriadou, Sofia, Hackett, Scott, Hague, Rosie, Haimel, Matthias, Harper, Lorraine, Hayman, Grant, Herwadkar, Archana, Hu, Fengyuan, Hughes, Stephen, Huissoon, Aarnoud P., James, Roger, Jolles, Stephen, Jolley, Jennifer, Jones, Julie, Karim, Yousuf, Kasanicki, Mary A., Kelleher, Peter, Kempster, Carly, Kiani, Sorena, Kingston, Nathalie, Klein, Nigel, Kostadima, Myrto, Kreuzhuber, Roman, Kuijpers, Taco W., Kumararatne, Dinakantha, Laffan, James, Allen, Hana Lango, Lear, Sara E., Linger, Rachel, Longhurst, Hilary, Lorenzo, Lorena E., Lyons, Paul A., Maimaris, Jesmeen, Manson, Ania, Mapeta, Rutendo, Martin, Jennifer, McCarthy, Mark I., McDermott, Elizabeth M., McKinney, Harriet, Meacham, Stuart, Megy, Karyn, Millar, Hazel, Mistry, Anoop, Morrisson, Valerie, Murng, Sai H.K., Nasir, Iman, Nejentsev, Sergey, Noorani, Sadia, Oksenhendler, Eric, Ouwehand, Willem H., Papadia, Sofia, Penkett, Christopher J., Petersen, Romina, Ponsford, Mark J., Qasim, Waseem, Quinn, Ellen, Quinti, Isabella, Raymond, F. Lucy, Rayner-Matthews, Paula J., Richter, Alex, Samani, Nilesh, Samarghitean, Crina, Sanchis-Juan, Alba, Sargur, Ravishankar B., Savic, Sinisa, Seneviratne, Suranjith L., Sewell, W.A. Carrock, Seyres, Denis, Shackley, Fiona, Shamardina, Olga, Simeoni, Ilenia, Simpson, Michael A., Smith, Kenneth G.C., Staines, Simon, Staples, Emily, Stark, Hannah, Stauss, Hans, Steele, Cathal L., Stephens, Jonathan, Stirrups, Kathleen E., Thaventhiran, James E., Thomas, David, Thomas, Moira J., Thomas, Patrick, Thrasher, Adrian J., Tilly, Tobias, Titterton, Catherine, Treadaway, Paul, Tuna, Salih, Turro, Ernest, Urniaz, Rafal, von Ziegenweidt, Julie, Walker, Neil, Watt, Christopher, Welch, Steven B., Whitehorn, Deborah, Willcocks, Lisa, Wood, Nicholas, Wood, Yvette, Workman, Sarita, Worth, Austen, Yates, Katherine, Yeatman, Nigel, Yong, Patrick F.K., Young, Timothy, Yu, Ping, Zlamalova, Eliska, Lorenzini, Tiziana, Fliegauf, Manfred, Klammer, Nils, Frede, Natalie, Proietti, Michele, Bulashevska, Alla, Camacho-Ordonez, Nadezhda, Varjosalo, Markku, Kinnunen, Matias, de Vries, Esther, van der Meer, Jos W.M., Ameratunga, Rohan, Roifman, Chaim M., Schejter, Yael D., Kobbe, Robin, Hautala, Timo, Atschekzei, Faranaz, Schmidt, Reinhold E., Schröder, Claudia, Stepensky, Polina, Shadur, Bella, Pedroza, Luis A., van der Flier, Michiel, Martínez-Gallo, Mónica, Gonzalez-Granado, Luis Ignacio, Allende, Luis M., Shcherbina, Anna, Kuzmenko, Natalia, Zakharova, Victoria, Neves, João Farela, Svec, Peter, Fischer, Ute, Ip, Winnie, Bartsch, Oliver, Barış, Safa, Klein, Christoph, Geha, Raif, Chou, Janet, Alosaimi, Mohammed, Weintraub, Lauren, Boztug, Kaan, Hirschmugl, Tatjana, Dos Santos Vilela, Maria Marluce, Holzinger, Dirk, Seidl, Maximilian, Lougaris, Vassilios, Plebani, Alessandro, Alsina, Laia, Piquer-Gibert, Monica, Deyà-Martínez, Angela, Slade, Charlotte A., Aghamohammadi, Asghar, Abolhassani, Hassan, Hammarström, Lennart, Kuismin, Outi, Helminen, Merja, Freeman, Alexandra F., Cook, Matthew, Bakhtiar, Shahrzad, Christiansen, Mette, Cunningham-Rundles, Charlotte, Patel, Niraj C., Rae, William, Niehues, Tim, Brauer, Nina, Syrjänen, Jaana, Seppänen, Mikko R.J., Tuijnenburg, Paul, Warnatz, Klaus, and Grimbacher, Bodo

Published
2020
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17. Whole-genome sequencing of patients with rare diseases in a national health system.

Author

Ernest Turro, William J. Astle, Karyn Megy, Stefan Gräf, Daniel Greene, Olga Shamardina, Hana Lango Allen, Alba Sanchis-Juan, Mattia Frontini, Chantal Thys, Jonathan Stephens, Rutendo Mapeta, Oliver S. Burren, Kate Downes, Matthias Haimel, Salih Tuna, Sri V. V. Deevi, Timothy J. Aitman, David L. H. Bennett, Paul Calleja, Keren Carss, Mark J. Caulfield, Patrick F. Chinnery, Peter H. Dixon, Daniel P. Gale, Roger James, Ania Koziell, Michael A. Laffan, Adam P. Levine, Eamonn R. Maher, Hugh S. Markus, Joannella Morales, Nicholas W. Morrell, Andrew D. Mumford, Elizabeth Ormondroyd, Stuart Rankin, Augusto Rendon, Sylvia Richardson, Irene Roberts, Noemi B. A. Roy, Moin A. Saleem, Kenneth G. C. Smith, Hannah Stark, Rhea Y. Y. Tan, Andreas C. Themistocleous, Adrian J. Thrasher, Hugh Watkins, Andrew R. Webster, Martin R. Wilkins, Catherine Williamson, James Whitworth, Sean Humphray, David R. Bentley, Stephen Abbs, Lara Abulhoul, Julian Adlard, Munaza Ahmed, Hana Alachkar, David J. Allsup, Jeff Almeida-King, Philip Ancliff, Richard Antrobus, Ruth Armstrong, Gavin Arno, Sofie Ashford, Anthony Attwood, Paul Aurora, Christian Babbs, Chiara Bacchelli, Tamam Bakchoul, Siddharth Banka, Tadbir Bariana, Julian Barwell, Joana Batista, Helen E. Baxendale, Phil L. Beales, Agnieszka Bierzynska, Tina Biss, Maria A. K. Bitner-Glindzicz, Graeme C. M. Black, Marta Bleda, Iulia Blesneac, Detlef Bockenhauer, Harm Bogaard, Christian J. Bourne, Sara Boyce, John R. Bradley, Eugene Bragin, Gerome Breen, Paul Brennan, Carole Brewer, Matthew Brown, Andrew C. Browning, Michael J. Browning, Rachel J. Buchan, Matthew S. Buckland, Teofila Bueser, Carmen Bugarin Diz, John Burn, Siobhan O. Burns, Nigel Burrows, Carolyn Campbell, Gerald Carr-White, Ruth Casey, Jenny Chambers, John Chambers, Melanie M. Y. Chan, Calvin Cheah, Floria Cheng, Manali Chitre, Martin T. Christian, Colin Church, Jill Clayton-Smith, Maureen Cleary, Naomi Clements Brod, Gerry Coghlan, Elizabeth Colby, Trevor R. P. Cole, Janine Collins, Peter W. Collins, Camilla Colombo, Cecilia J. Compton, Robin Condliffe, Stuart A. Cook, H. Terence Cook, Nichola Cooper, Paul A. Corris, Abigail Furnell, Fiona Cunningham, Nicola S. Curry, Antony J. Cutler, Matthew J. Daniels, Mehul Dattani, Louise C. Daugherty, John Davis, Anthony De Soyza, Timothy Dent, Charu Deshpande, Eleanor F. Dewhurst, Sofia Douzgou, Anna M. Drazyk, Elizabeth Drewe, Daniel Duarte, Tina Dutt, J. David M. Edgar, Karen Edwards, William Egner, Melanie N. Ekani, Perry Elliott, Wendy N. Erber, Marie Erwood, Maria C. Estiu, Dafydd Gareth Evans, Gillian Evans, Tamara Everington, Mélanie Eyries, Hiva Fassihi, Remi Favier, Jack Findhammer, Debra Fletcher, Frances A. Flinter, R. Andres Floto, Tom Fowler, James Fox, Amy J. Frary, Courtney E. French, Kathleen Freson, Henning Gall, Vijeya Ganesan, Michael Gattens, Claire Geoghegan, Terence S. A. Gerighty, Ali G. Gharavi, Stefano Ghio, Hossein-Ardeschir Ghofrani, J. Simon R. Gibbs, Kate Gibson, Kimberly C. Gilmour, Barbara Girerd, Nicholas S. Gleadall, Sarah Goddard, David B. Goldstein, Keith Gomez, Pavels Gordins, David Gosal, Jodie Graham, Luigi Grassi, Lynn Greenhalgh, Andreas Greinacher, Paolo Gresele, Philip Griffiths, Sofia Grigoriadou, Russell J. Grocock, Detelina Grozeva, Mark Gurnell, Scott Hackett, Charaka Hadinnapola, William M. Hague, Rosie Hague, Matthew Hall, Helen L. Hanson, Eshika Haque, Kirsty Harkness, Andrew R. Harper, Claire L. Harris, Daniel Hart, Ahamad Hassan, Grant Hayman, Alex Henderson, Archana Herwadkar, Jonathan Hoffman, Simon Holden, Rita Horvath, Henry Houlden, Arjan C. Houweling, Luke S. G. E. Howard, Fengyuan Hu, Gavin Hudson, Joseph Hughes, Aarnoud P. Huissoon, Marc Humbert, Sarah Hunter, Matthew E. Hurles, Melita Irving, Louise Izatt, Sally A. Johnson, Stephen Jolles, Jennifer Jolley, Dragana Josifova, Neringa Jurkute, Tim Karten, Johannes Karten, Mary A. Kasanicki, Hanadi Kazkaz, Rashid Kazmi, Peter Kelleher, Anne M. Kelly, Wilf Kelsall, Carly Kempster, David G. Kiely, Nathalie Kingston, Robert Klima, Nils Koelling, Myrto Kostadima, Gabor Kovacs, Roman Kreuzhuber, Taco W. Kuijpers, Ajith Kumar, Dinakantha Kumararatne, Manju A. Kurian, Fiona Lalloo, Michele Lambert, Allan Lawrie, D. Mark Layton, Nick Lench, Claire Lentaigne, Tracy Lester, Rachel Linger, Hilary Longhurst, Lorena E. Lorenzo, Eleni Louka, Paul A. Lyons, Rajiv D. Machado, Robert V. MacKenzie Ross, Bella Madan, Jesmeen Maimaris, Samantha Malka, Sarah Mangles, Kevin J. Marchbank, Stephen Marks, Hanns-Ulrich Marschall, Andrew G. Marshall, Jennifer Martin, Mary Mathias, Emma Matthews, Heather Maxwell, Paul McAlinden, Mark I. McCarthy, Harriet McKinney, Aoife McMahon, Stuart Meacham, Adam J. Mead, Ignacio Medina Castello, Sarju G. Mehta, Michel Michaelides, Carolyn Millar, Shehla N. Mohammed, Shahin Moledina, David Montani, Anthony T. Moore, Monika Mozere, Keith W. Muir, Andrea H. Nemeth, William G. Newman, Michael Newnham, Sadia Noorani, Paquita Nurden, Jennifer O'Sullivan, Samya Obaji, Chris Odhams, Steven Okoli, Andrea Olschewski, Horst Olschewski, Kai Ren Ong, S. Helen Oram, Willem H. Ouwehand, Claire Palles, Sofia Papadia, Soo-Mi Park, David Parry 0003, Smita Patel, Joan Paterson, Andrew Peacock, Simon H. Pearce, John Peden, Kathelijne Peerlinck, Christopher J. Penkett, Joanna Pepke-Zaba, Romina Petersen, Clarissa Pilkington, Kenneth E. S. Poole, Radhika Prathalingam, Bethan Psaila, Angela Pyle, Richard Quinton, Shamima Rahman, Anupama Rao, F. Lucy Raymond, Paula J. Rayner-Matthews, Christine Rees, Tara Renton, Christopher J. Rhodes, Andrew S. C. Rice, Alex Richter, Leema Robert, Anthony Rogers, Sarah J. Rose, Robert Ross-Russell, Catherine Roughley, Deborah M. Ruddy, Omid Sadeghi-Alavijeh, Nilesh J. Samani, Crina Samarghitean, Ravishankar B. Sargur, Robert N. Sarkany, Simon Satchell, Sinisa Savic, John A. Sayer, Genevieve Sayer, Laura Scelsi, Andrew M. Schaefer, Sol Schulman, Richard Scott, Marie Scully, Claire Searle, Werner Seeger, Arjune Sen, W. A. Carrock Sewell, Denis Seyres, Neil Shah, Susan E. Shapiro, Adam C. Shaw, Patrick J. Short, Keith Sibson, Lucy Side, Ilenia Simeoni, Michael A. Simpson, Matthew C. Sims, Suthesh Sivapalaratnam, Damian Smedley, Katherine R. Smith, Katie Snape, Nicole Soranzo, Florent Soubrier, Laura Southgate, Olivera Spasic-Boskovic, Simon Staines, Emily Staples, Charles A. Steward, Kathleen E. Stirrups, Alex Stuckey, Jay Suntharalingam, Emilia M. Swietlik, Petros Syrris, R. Campbell Tait, Kate Talks, Katie Tate, John M. Taylor, Jenny C. Taylor, James E. Thaventhiran, Ellen Thomas, David Thomas 0004, Moira J. Thomas, Patrick Thomas, Kate Thomson, Glen Threadgold, Tobias Tilly, Marc Tischkowitz, Catherine Titterton, John A. Todd, Cheng-Hock Toh, Bas Tolhuis, Ian P. Tomlinson, Mark Toshner, Matthew Traylor, Carmen Treacy, Paul Treadaway, Richard Trembath, Wojciech Turek, Philip Twiss, Tom Vale, Chris Van Geet, Natalie van Zuydam, Maarten Vandekuilen, Anthony M. Vandersteen, Marta Vazquez-Lopez, Julie von Ziegenweidt, Anton Vonk-Noordegraaf, Annette Wagner, Quinten Waisfisz, Suellen M. Walker, Neil Walker, Klaudia Walter, James S. Ware, Christopher Watt, Lucy Wedderburn, Wei Wei, Steven B. Welch, Julie Wessels, Sarah K. Westbury, John-Paul Westwood, John Wharton, Deborah Whitehorn, Andrew O. M. Wilkie, Brian T. Wilson, Edwin K. S. Wong, Nicholas W. Wood, Yvette Wood, Christopher Geoffrey Woods, Emma R. Woodward, Stephen J. Wort, Austen Worth, Michael Wright, Katherine Yates, Patrick F. K. Yong, Timothy Young, Ping Yu, Patrick Yu-Wai-Man, and Eliska Zlamalova

Published
2020
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20. Long‐term safety and effectiveness of berotralstat for hereditary angioedema: The open‐label APeX‐S study

Author

Henriette Farkas, Marcin Stobiecki, Jonny Peter, Tamar Kinaciyan, Marcus Maurer, Emel Aygören‐Pürsün, Sorena Kiani‐Alikhan, Adrian Wu, Avner Reshef, Anette Bygum, Olivier Fain, David Hagin, Aarnoud Huissoon, Miloš Jeseňák, Karen Lindsay, Vesna Grivcheva Panovska, Urs C. Steiner, Celia Zubrinich, Jessica M. Best, Melanie Cornpropst, Daniel Dix, Sylvia M. Dobo, Heather A. Iocca, Bhavisha Desai, Sharon C. Murray, Eniko Nagy, and William P. Sheridan

Subjects
berotralstat, hereditary angioedema, long‐term, prophylaxis, safety, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Berotralstat (BCX7353) is an oral, once‐daily inhibitor of plasma kallikrein recently approved for prevention of angioedema attacks in adults and adolescents with hereditary angioedema (HAE). The objective of this report is to summarize results from an interim analysis of an ongoing long‐term safety study of berotralstat in patients with HAE. Methods APeX‐S is an ongoing, phase 2, open‐label study conducted in 22 countries (ClinicalTrials.gov, NCT03472040). Eligible patients with a clinical diagnosis of HAE due to C1 inhibitor deficiency (HAE‐C1‐INH) were centrally allocated to receive berotralstat 150 or 110 mg once daily. The primary objective was to determine long‐term safety and the secondary objective was to evaluate effectiveness. Results Enrolled patients (N = 227) received berotralstat 150 mg (n = 127) or 110 mg (n = 100) once daily. The median (range) duration of exposure was 342 (11–540) and 307 (14–429) days for the 150‐mg and 110‐mg groups, respectively. Treatment‐emergent adverse events (TEAEs) occurred in 91% (n = 206) of patients. The most common TEAEs across treatment groups were upper respiratory tract infection (n = 91, 40%), abdominal pain (n = 57, 25%), headache (n = 40, 18%), and diarrhea (n = 31, 14%) and were mostly mild to moderate. Fifty percent (n = 113) of patients had at least one drug‐related adverse event (AE; 150 mg, n = 57 [45%]; 110 mg, n = 56 [56%]), and discontinuations due to AEs occurred in 19 (8%) patients (150 mg, n = 13 [10%]; 110 mg, n = 6 [6%]). Three (1.3%) patients experienced a drug‐related serious TEAE. Among patients who received berotralstat through 48 weeks (150 mg, n = 73; 110 mg, n = 30), median HAE attack rates were low in month 1 (150 mg, 1.0 attacks/month; 110 mg, 0.5 attacks/month) and remained low through 12 months (0 attacks/month in both dose groups). Mean HAE attack rates followed a similar trend, and no evidence for patient tolerance to berotralstat emerged. In both dose groups, angioedema quality of life scores showed clinically meaningful changes from baseline. Conclusions In this analysis, both berotralstat doses, 150 and 110 mg once daily, were generally well tolerated. Effectiveness results support the durability and robustness of berotralstat as prophylactic therapy in patients with HAE. Trial registration The study is registered with ClinicalTrials.gov (NCT03472040).

Published
2021
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21. Loss-of-function nuclear factor κB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans

Author

Adhya, Zoe, Alachkar, Hana, Anantharachagan, Ariharan, Antrobus, Richard, Arumugakani, Gururaj, Bacchelli, Chiara, Baxendale, Helen, Bethune, Claire, Bibi, Shahnaz, Boardman, Barbara, Booth, Claire, Browning, Michael, Brownlie, Mary, Burns, Siobhan, Chandra, Anita, Clifford, Hayley, Cooper, Nichola, Davies, Sophie, Dempster, John, Devlin, Lisa, Doffinger, Rainer, Drewe, Elizabeth, Edgar, David, Egner, William, El-Shanawany, Tariq, Gaspar, Bobby, Ghurye, Rohit, Gilmour, Kimberley, Goddard, Sarah, Gordins, Pavel, Grigoriadou, Sofia, Hackett, Scott, Hague, Rosie, Harper, Lorraine, Hayman, Grant, Herwadkar, Archana, Hughes, Stephen, Huissoon, Aarnoud, Jolles, Stephen, Jones, Julie, Kelleher, Peter, Klein, Nigel, Kuijpers, Taco, Kumararatne, Dinakantha, Laffan, James, Lango Allen, Hana, Lear, Sara, Longhurst, Hilary, Lorenzo, Lorena, Maimaris, Jesmeen, Manson, Ania, McDermott, Elizabeth, Millar, Hazel, Mistry, Anoop, Morrisson, Valerie, Murng, Sai, Nasir, Iman, Nejentsev, Sergey, Noorani, Sadia, Oksenhendler, Eric, Ponsford, Mark, Qasim, Waseem, Quinn, Ellen, Quinti, Isabella, Richter, Alex, Samarghitean, Crina, Sargur, Ravishankar, Savic, Sinisa, Seneviratne, Suranjith, Sewall, Carrock, Shackley, Fiona, Simeoni, Ilenia, Smith, Kenneth G.C., Staples, Emily, Stauss, Hans, Steele, Cathal, Thaventhiran, James, Thomas, Moira, Thrasher, Adrian, Welch, Steve, Willcocks, Lisa, Workman, Sarita, Worth, Austen, Yeatman, Nigel, Yong, Patrick, Ashford, Sofie, Bradley, John, Fletcher, Debra, Hammerton, Tracey, James, Roger, Kingston, Nathalie, Ouwehand, Willem, Penkett, Christopher, Raymond, F Lucy, Stirrups, Kathleen, Veltman, Marijke, Young, Tim, Brown, Matthew, Clements-Brod, Naomi, Davis, John, Dewhurst, Eleanor, Erwood, Marie, Frary, Amy, Linger, Rachel, Martin, Jennifer, Papadia, Sofia, Rehnstrom, Karola, Astle, William, Attwood, Antony, Bleda, Marta, Carss, Keren, Daugherty, Louise, Deevi, Sri, Graf, Stefan, Greene, Daniel, Halmagyi, Csaba, Haimel, Matthias, Hu, Fengyuan, Matser, Vera, Meacham, Stuart, Megy, Karyn, Shamardina, Olga, Titterton, Catherine, Tuna, Salih, Turro, Ernest, Yu, Ping, von Ziegenweldt, Julie, Furnell, Abigail, Mapeta, Rutendo, Staines, Simon, Stephens, Jonathan, Whitehorn, Deborah, Rayner-Matthews, Paula, Watt, Christopher, Tuijnenburg, Paul, Burns, Siobhan O., Jansen, Machiel H., Carss, Keren J., Biasci, Daniele, Kiani-Alikhan, Sorena, Longhurst, Hilary J., Seneviratne, Suranjith L., de Bree, Godelieve J., Tool, Anton T.J., van Leeuwen, Ester M.M., Ebberink, Eduard H.T.M., Meijer, Alexander B., Thrasher, Adrian J., Thaventhiran, James E., and Kuijpers, Taco W.

Published
2018
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22. Comprehensive Cancer-Predisposition Gene Testing in an Adult Multiple Primary Tumor Series Shows a Broad Range of Deleterious Variants and Atypical Tumor Phenotypes

Author

Aitman, Timothy, Alachkar, Hana, Ali, Sonia, Allen, Louise, Allsup, David, Ambegaonkar, Gautum, Anderson, Julie, Antrobus, Richard, Armstrong, Ruth, Arno, Gavin, Arumugakani, Gururaj, Ashford, Sofie, Astle, William, Attwood, Antony, Austin, Steve, Bacchelli, Chiara, Bakchoul, Tamam, Bariana, Tadbir K., Baxendale, Helen, Bennett, David, Bethune, Claire, Bibi, Shahnaz, Bitner-Glindzicz, Maria, Bleda, Marta, Boggard, Harm, Bolton-Maggs, Paula, Booth, Claire, Bradley, John R., Brady, Angie, Brown, Matthew, Browning, Michael, Bryson, Christine, Burns, Siobhan, Calleja, Paul, Canham, Natalie, Carmichael, Jenny, Carss, Keren, Caulfield, Mark, Chalmers, Elizabeth, Chandra, Anita, Chinnery, Patrick, Chitre, Manali, Church, Colin, Clement, Emma, Clements-Brod, Naomi, Clowes, Virginia, Coghlan, Gerry, Collins, Peter, Cookson, Victoria, Cooper, Nichola, Corris, Paul, Creaser-Myers, Amanda, DaCosta, Rosa, Daugherty, Louise, Davies, Sophie, Davis, John, De Vries, Minka, Deegan, Patrick, Deevi, Sri V.V., Deshpande, Charu, Devlin, Lisa, Dewhurst, Eleanor, Dixon, Peter, Doffinger, Rainer, Dormand, Natalie, Drewe, Elizabeth, Edgar, David, Egner, William, Erber, Wendy N., Erwood, Marie, Everington, Tamara, Favier, Remi, Firth, Helen, Fletcher, Debra, Flinter, Frances, Frary, Amy, Freson, Kathleen, Furie, Bruce, Furnell, Abigail, Gale, Daniel, Gardham, Alice, Gattens, Michael, Ghali, Neeti, Ghataorhe, Pavandeep K., Ghurye, Rohit, Gibbs, Simon, Gilmour, Kimberley, Gissen, Paul, Goddard, Sarah, Gomez, Keith, Gordins, Pavel, Graf, Stefan, Gräf, Stefan, Greene, Daniel, Greenhalgh, Alan, Greinacher, Andreas, Grigoriadou, Sofia, Grozeva, Detelina, Hackett, Scott, Hadinnapola, Charaka, Hague, Rosie, Haimel, Matthias, Halmagyi, Csaba, Hammerton, Tracey, Hart, Daniel, Hayman, Grant, Heemskerk, Johan W.M., Henderson, Robert, Hensiek, Anke, Henskens, Yvonne, Herwadkar, Archana, Holden, Simon, Holder, Muriel, Holder, Susan, Hu, Fengyuan, Huis in’t Veld, Anna, Huissoon, Aarnoud, Humbert, Marc, Hurst, Jane, James, Roger, Jolles, Stephen, Josifova, Dragana, Kazmi, Rashid, Keeling, David, Kelleher, Peter, Kelly, Anne M., Kennedy, Fiona, Kiely, David, Kingston, Nathalie, Koziell, Ania, Krishnakumar, Deepa, Kuijpers, Taco W., Kuijpers, Taco, Kumararatne, Dinakantha, Kurian, Manju, Laffan, Michael A., Lambert, Michele P., Allen, Hana Lango, Lango-Allen, Hana, Lawrie, Allan, Lear, Sara, Lees, Melissa, Lentaigne, Claire, Liesner, Ri, Linger, Rachel, Longhurst, Hilary, Lorenzo, Lorena, Louka, Eleni, Machado, Rajiv, Ross, Rob Mackenzie, MacLaren, Robert, Maher, Eamonn, Maimaris, Jesmeen, Mangles, Sarah, Manson, Ania, Mapeta, Rutendo, Markus, Hugh S., Martin, Jennifer, Masati, Larahmie, Mathias, Mary, Matser, Vera, Maw, Anna, McDermott, Elizabeth, McJannet, Coleen, Meacham, Stuart, Meehan, Sharon, Megy, Karyn, Mehta, Sarju, Michaelides, Michel, Millar, Carolyn M., Moledina, Shahin, Moore, Anthony, Morrell, Nicholas, Mumford, Andrew, Murng, Sai, Murphy, Elaine, Nejentsev, Sergey, Noorani, Sadia, Nurden, Paquita, Oksenhendler, Eric, Othman, Shokri, Ouwehand, Willem H., Papadia, Sofia, Park, Soo-Mi, Parker, Alasdair, Pasi, John, Patch, Chris, Paterson, Joan, Payne, Jeanette, Peacock, Andrew, Peerlinck, Kathelijne, Penkett, Christopher J., Pepke-Zaba, Joanna, Perry, David, Perry, David J., Pollock, Val, Polwarth, Gary, Ponsford, Mark, Qasim, Waseem, Quinti, Isabella, Rankin, Stuart, Rankin, Julia, Raymond, F. Lucy, Rayner-Matthews, Paula, Rehnstrom, Karola, Reid, Evan, Rhodes, Christopher J., Richards, Michael, Richardson, Sylvia, Richter, Alex, Roberts, Irene, Rondina, Matthew, Rosser, Elisabeth, Roughley, Catherine, Roy, Noémi, Rue-Albrecht, Kevin, Samarghitean, Crina, Sanchis-Juan, Alba, Sandford, Richard, Santra, Saikat, Sargur, Ravishankar, Savic, Sinisa, Schotte, Gwen, Schulman, Sol, Schulze, Harald, Scott, Richard, Scully, Marie, Seneviratne, Suranjith, Sewell, Carrock, Shamardina, Olga, Shipley, Debbie, Simeoni, Ilenia, Sivapalaratnam, Suthesh, Smith, Kenneth G.C., Sohal, Aman, Southgate, Laura, Staines, Simon, Staples, Emily, Stark, Hannah, Stauss, Hans, Stein, Penelope, Stephens, Jonathan, Stirrups, Kathleen, Stock, Sophie, Suntharalingam, Jay, Talks, Kate, Tan, Yvonne, Thachil, Jecko, Thaventhiran, James, Thomas, Ellen, Thomas, Moira, Thompson, Dorothy, Thrasher, Adrian, Tischkowitz, Marc, Titterton, Catherine, Toh, Cheng-Hock, Toshner, Mark, Treacy, Carmen, Trembath, Richard, Tuna, Salih, Turek, Wojciech, Turro, Ernest, Van Geet, Chris, Veltman, Marijke, Vogt, Julie, von Ziegenweldt, Julie, Vonk Noordegraaf, Anton, Wakeling, Emma, Wanjiku, Ivy, Warner, Timothy Q., Wassmer, Evangeline, Watkins, Hugh, Watt, Christopher, Webster, ndrew, Welch, Steve, Westbury, Sarah, Wharton, John, Whitehorn, Deborah, Wilkins, Martin, Willcocks, Lisa, Williamson, Catherine, Woods, Geoffrey, Woods, Geoff, Wort, John, Yeatman, Nigel, Yong, Patrick, Young, Tim, Yu, Ping, Whitworth, James, Smith, Philip S., Martin, Jose-Ezequiel, West, Hannah, Luchetti, Andrea, Rodger, Faye, Clark, Graeme, Penkett, Chris, Shakeel, Hassan, Ahmed, Munaza, Adlard, Julian, Barwell, Julian, Brewer, Carole, Casey, Ruth T., Cole, Trevor, Evans, Dafydd Gareth, Fostira, Florentia, Greenhalgh, Lynn, Hanson, Helen, Henderson, Alex, Hoffman, Jonathan, Izatt, Louise, Kumar, Ajith, Kwong, Ava, Lalloo, Fiona, Ong, Kai Ren, Chen-Shtoyerman, Rakefet, Searle, Claire, Side, Lucy, Skytte, Anne-Bine, Snape, Katie, Woodward, Emma R., Tischkowitz, Marc D., and Maher, Eamonn R.

Published
2018
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24. µPump: An open-source pressure pump for precision fluid handling in microfluidics

Author

Run Ze Gao, Marie Hébert, Jan Huissoon, and Carolyn L. Ren

Subjects
Open-source hardware, Microfluidics, Pneumatics, Laboratory automation, Fluid handling, Lab on a chip, Science (General), Q1-390
Abstract

An open-source precision pressure pump system and control software is presented, primarily designed for the experimental microfluidics community, although others may find additional uses for this precision pressure source. This mechatronic system is coined ‘µPump,’ and its performance rivals that of commercially available systems, at a fraction of the cost. The pressure accuracy, stability, and resolution are 0.09%, 0.02%, and 0.02% of the full span, respectively. The settling time to reach 2 bar from zero and stabilize is less than 2 s. Material for building a four-channel µPump (approx. $3000 USD) or an eight-channel µPump (approx. $5000 USD) is approximately a quarter, or a third of the cost of buying a high-end commercial system, respectively. The design rationale is presented, together with documented design details and software, so that the system may be replicated or customized to particular applications. µPump can be used for two-phase droplet microfluidics, single-phase microfluidics, gaseous flow microfluidics and any other applications requiring precise fluid handling. µPump provides researchers, students, and startups with a cost-effective solution for precise fluid control.

Published
2020
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25. An integrated microfluidic device for the sorting of yeast cells using image processing

Author

Bo Yang Yu, Caglar Elbuken, Chong Shen, Jan Paul Huissoon, and Carolyn L. Ren

Subjects
Medicine, Science
Abstract

Abstract The process of detection and separation of yeast cells based on their morphological characteristics is critical to the understanding of cell division cycles, which is of vital importance to the understanding of some diseases such as cancer. The traditional process of manual detection is usually tedious and inconsistent. This paper presents a microfluidic device integrated with microvalves for fluid control for the sorting of yeast cells using image processing algorithms and confirmation based on their fluorescent tag. The proposed device is completely automated, low cost and easy to implement in an academic research setting. Design details of the integrated microfluidic system are highlighted in this paper, along with experimental validation. Real time cell sorting was demonstrated with a cell detection rate of 12 cells per minute.

Published
2018
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27. British Lung Foundation/United Kingdom Primary Immunodeficiency Network Consensus Statement on the Definition, Diagnosis, and Management of Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency Disorders

Author

Hurst, John R., Verma, Nisha, Lowe, David, Baxendale, Helen E., Jolles, Stephen, Kelleher, Peter, Longhurst, Hilary J., Patel, Smita Y., Renzoni, Elisabetta A., Sander, Clare R., Avery, Gerard R., Babar, Judith L., Buckland, Matthew S., Burns, Siobhan, Egner, William, Gompels, Mark M., Gordins, Pavels, Haddock, Jamanda A., Hart, Simon P., Hayman, Grant R., Herriot, Richard, Hoyles, Rachel K., Huissoon, Aarnoud P., Jacob, Joseph, Nicholson, Andrew G., Rassl, Doris M., Sargur, Ravishankar B., Savic, Sinisa, Seneviratne, Suranjith L., Sheaff, Michael, Vaitla, Prashantha M., Walters, Gareth I., Whitehouse, Joanna L., Wright, Penny A., and Condliffe, Alison M.

Published
2017
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29. The impact of anaphylaxis on the quality of life and mental health of adults

Author

Rebecca Knibb, Aarnoud Huissoon, Richard Baretto, Anjali Ekbote, Sham Onyango-Odera, Cassandra Screti, Kristina Newman L, and MAMIDIPUDI THIRUMALA KRISHNA

Subjects
Immunology, Immunology and Allergy
Abstract

Background. Anaphylaxis is a severe and potentially life-threatening allergic reaction which has a detrimental impact on quality of life (QoL), however little is known about the impact of anaphylaxis, across the various causes, on adults. The aim of this study was to assess the impact of anaphylaxis on QoL and mental health in adults. Methods. Participants (n=142; 60% female) were recruited from a regional allergy centre (Birmingham, U.K) following systematic specialist evaluation. They completed measures of generic QoL (WHOQoL BREF), anaphylaxis specific QoL (A-QoL-Adults), anxiety and depression (HADS) and stress (PSS). Results. Anaphylaxis triggers were mainly to medication or during general anaesthesia (29.6%), food (29.6%), wasp or bee venom (16.2%), or were spontaneous (21.1%). Adults with anaphylaxis had significantly poorer general QoL and stress than published data from a healthy population. Females had significantly poorer anxiety and depression than norm data (all pConclusions. Anaphylaxis has an adverse impact on QoL and mental health of adults across different triggers. Anxiety, depression and number of reactions in particular seem to be important in explaining the impact on QoL and should be of particular note for clinicians managing adults with this condition, and when considering specialist psychological support.

Published
2022
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30. Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Author

Aitman, Timothy, Alachkar, Hana, Ali, Sonia, Allen, Louise, Allsup, David, Ambegaonkar, Gautum, Anderson, Julie, Antrobus, Richard, Armstrong, Ruth, Arno, Gavin, Arumugakani, Gururaj, Ashford, Sofie, Astle, William, Attwood, Antony, Austin, Steve, Bacchelli, Chiara, Bakchoul, Tamam, Bariana, Tadbir K., Baxendale, Helen, Bennett, David, Bethune, Claire, Bibi, Shahnaz, Bitner-Glindzicz, Maria, Bleda, Marta, Boggard, Harm, Bolton-Maggs, Paula, Booth, Claire, Bradley, John R., Brady, Angie, Brown, Matthew, Browning, Michael, Bryson, Christine, Burns, Siobhan, Calleja, Paul, Canham, Natalie, Carmichael, Jenny, Carss, Keren, Caulfield, Mark, Chalmers, Elizabeth, Chandra, Anita, Chinnery, Patrick, Chitre, Manali, Church, Colin, Clement, Emma, Clements-Brod, Naomi, Clowes, Virginia, Coghlan, Gerry, Collins, Peter, Cooper, Nichola, Creaser-Myers, Amanda, DaCosta, Rosa, Daugherty, Louise, Davies, Sophie, Davis, John, De Vries, Minka, Deegan, Patrick, Deevi, Sri V.V., Deshpande, Charu, Devlin, Lisa, Dewhurst, Eleanor, Doffinger, Rainer, Dormand, Natalie, Drewe, Elizabeth, Edgar, David, Egner, William, Erber, Wendy N., Erwood, Marie, Everington, Tamara, Favier, Remi, Firth, Helen, Fletcher, Debra, Flinter, Frances, Fox, James C., Frary, Amy, Freson, Kathleen, Furie, Bruce, Furnell, Abigail, Gale, Daniel, Gardham, Alice, Gattens, Michael, Ghali, Neeti, Ghataorhe, Pavandeep K., Ghurye, Rohit, Gibbs, Simon, Gilmour, Kimberley, Gissen, Paul, Goddard, Sarah, Gomez, Keith, Gordins, Pavel, Gräf, Stefan, Greene, Daniel, Greenhalgh, Alan, Greinacher, Andreas, Grigoriadou, Sofia, Grozeva, Detelina, Hackett, Scott, Hadinnapola, Charaka, Hague, Rosie, Haimel, Matthias, Halmagyi, Csaba, Hammerton, Tracey, Hart, Daniel, Hayman, Grant, Heemskerk, Johan W.M., Henderson, Robert, Hensiek, Anke, Henskens, Yvonne, Herwadkar, Archana, Holden, Simon, Holder, Muriel, Holder, Susan, Hu, Fengyuan, Huissoon, Aarnoud, Humbert, Marc, Hurst, Jane, James, Roger, Jolles, Stephen, Josifova, Dragana, Kazmi, Rashid, Keeling, David, Kelleher, Peter, Kelly, Anne M., Kennedy, Fiona, Kiely, David, Kingston, Nathalie, Koziell, Ania, Krishnakumar, Deepa, Kuijpers, Taco W., Kumararatne, Dinakantha, Kurian, Manju, Laffan, Michael A., Lambert, Michele P., Allen, Hana Lango, Lawrie, Allan, Lear, Sara, Lees, Melissa, Lentaigne, Claire, Liesner, Ri, Linger, Rachel, Longhurst, Hilary, Lorenzo, Lorena, Machado, Rajiv, Mackenzie, Rob, MacLaren, Robert, Maher, Eamonn, Maimaris, Jesmeen, Mangles, Sarah, Manson, Ania, Mapeta, Rutendo, Markus, Hugh S., Martin, Jennifer, Masati, Larahmie, Mathias, Mary, Matser, Vera, Maw, Anna, McDermott, Elizabeth, McJannet, Coleen, Meacham, Stuart, Meehan, Sharon, Megy, Karyn, Mehta, Sarju, Michaelides, Michel, Millar, Carolyn M., Moledina, Shahin, Moore, Anthony, Morrell, Nicholas, Mumford, Andrew, Murng, Sai, Murphy, Elaine, Nejentsev, Sergey, Noorani, Sadia, Nurden, Paquita, Oksenhendler, Eric, Ouwehand, Willem H., Papadia, Sofia, Park, Soo-Mi, Parker, Alasdair, Pasi, John, Patch, Chris, Paterson, Joan, Payne, Jeanette, Peacock, Andrew, Peerlinck, Kathelijne, Penkett, Christopher J., Pepke-Zaba, Joanna, Perry, David J., Pollock, Val, Polwarth, Gary, Ponsford, Mark, Qasim, Waseem, Quinti, Isabella, Rankin, Stuart, Rankin, Julia, Raymond, F. Lucy, Rehnstrom, Karola, Reid, Evan, Rhodes, Christopher J., Richards, Michael, Richardson, Sylvia, Richter, Alex, Roberts, Irene, Rondina, Matthew, Rosser, Elisabeth, Roughley, Catherine, Rue-Albrecht, Kevin, Samarghitean, Crina, Sanchis-Juan, Alba, Sandford, Richard, Santra, Saikat, Sargur, Ravishankar, Savic, Sinisa, Schulman, Sol, Schulze, Harald, Scott, Richard, Scully, Marie, Seneviratne, Suranjith, Sewell, Carrock, Shamardina, Olga, Shipley, Debbie, Simeoni, Ilenia, Sivapalaratnam, Suthesh, Smith, Kenneth, Sohal, Aman, Southgate, Laura, Staines, Simon, Staples, Emily, Stauss, Hans, Stein, Penelope, Stephens, Jonathan, Stirrups, Kathleen, Stock, Sophie, Suntharalingam, Jay, Tait, R. Campbell, Talks, Kate, Tan, Yvonne, Thachil, Jecko, Thaventhiran, James, Thomas, Ellen, Thomas, Moira, Thompson, Dorothy, Thrasher, Adrian, Tischkowitz, Marc, Titterton, Catherine, Toh, Cheng-Hock, Toshner, Mark, Treacy, Carmen, Trembath, Richard, Tuna, Salih, Turek, Wojciech, Turro, Ernest, Van Geet, Chris, Veltman, Marijke, Vogt, Julie, von Ziegenweldt, Julie, Vonk Noordegraaf, Anton, Wakeling, Emma, Wanjiku, Ivy, Warner, Timothy Q., Wassmer, Evangeline, Watkins, Hugh, Webster, Andrew, Welch, Steve, Westbury, Sarah, Wharton, John, Whitehorn, Deborah, Wilkins, Martin, Willcocks, Lisa, Williamson, Catherine, Woods, Geoffrey, Wort, John, Yeatman, Nigel, Yong, Patrick, Young, Tim, Yu, Ping, Carss, Keren J., Hull, Sarah, Malka, Samantha, Plagnol, Vincent, Penkett, Christopher, Rizzo, Roberta, Wright, Genevieve, Scott, Richard H., Brady, Angela F., Henderson, Robert H.H., MacLaren, Robert E., Thompson, Dorothy A., Moore, Anthony T., and Webster, Andrew R.

Published
2017
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31. Prescribing Immunoglobulin Replacement Therapy for Patients with Non-classical and Secondary Antibody Deficiency: an Analysis of the Practice of Clinical Immunologists in the UK and Republic of Ireland

Author

Edgar, John David M., Richter, Alex G., Huissoon, Aarnoud P., Kumararatne, Dinakantha S., Baxendale, Helen E., Bethune, Claire A., Garcez, Tomaz, Misbah, Siraj A., Sorensen, Ricardo U., and United Kingdom Primary Immunodeficiency Network (UKPIN) Immunoglobulin Decision to Treat Study Group

Published
2018
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32. Abstracts from the 10th C1-inhibitor deficiency workshop

Author

Alvin H. Schmaier, Marco Cicardi, Avner Reshef, Dumitru Moldovan, Attila Mócsai, Margarita López-Trascasa, Alberto López Lera, Nancy J. Brown, Anastasios E. Germenis, Rafael Filippelli-Silva, Diego A. Duarte, Renan P. Martin, Camila L. Veronez, Michel Bouvier, Michael Bader, Claudio M. Costa-Neto, João Bosco Pesquero, Xavier Charest-Morin, François Marceau, Georges-É. Rivard, Arnaud Bonnefoy, Éric Wagner, Márta L. Debreczeni, Zsuzsanna Németh, Erika Kajdácsi, Endre Schwaner, László Cervenak, Gábor Oroszlán, András Szilágyi, Ráhel Dani, Péter Závodszky, Péter Gál, József Dobó, Jacques Hébert, Matthieu Vincent, Jean-Nicolas Boursiquot, Hugo Chapdeleine, Marylin Desjardins, Benoit Laramée, Rémi Gagnon, Nancy Payette, Oleksandra Lepeshkina, Delphine Charignon, Arije Ghannam, Denise Ponard, Christian Drouet, Kusumam Joseph, Baby G. Tholanikunnel, Daniel J. Sexton, Allen P. Kaplan, Stefania Loffredo, Maria Bova, Anne Lise Ferrara, Angelica Petraroli, Chiara Suffritti, Nóra Veszeli, Andrea Zanichelli, Henriette Farkas, Gianni Marone, Samuel Luyasu, Bertrand Favier, Ludovic Martin, Kinga Viktória Kőhalmi, György Temesszentandrási, Katalin Várnai, Lilian Varga, Bruce L. Zuraw, Annette Feussner, Michael A. Tortorici, Dipti Pawaskar, Huamin Henry Li, John Anderson, Jonathan A. Bernstein, Ying Zhang, Ingo Pragst, on behalf of COMPACT investigators, Emel Aygören-Pürsün, Kraig Jacobson, Jim Christensen, Arthur Van Leerberghe, Yi Wang, Jennifer Schranz, Inmaculada Martinez-Saguer, Daniel Soteres, Urs Steiner, Vesna Grivcheva Panovska, William Rae, Werner Aberer, Aarnoud Huissoon, Anette Bygum, Markus Magerl, Jochen Graff, Hilary Longhurst, Ramón Lleonart, Lei Fang, Melanie Cornpropst, Desiree Clemons, Amanda Mathis, Phil Collis, Sylvia Dobo, William P. Sheridan, Marcus Maurer, Marc A. Riedl, Timothy Craig, Aleena Banerji, Mustafa Shennak, William Yang, Jovanna Baptista, Paula Busse, Ira Kalfus, Andrew McDonald, Shawn Qian, Anthony Roberts, Con Panousis, Tim Green, Andreas Gille, Maria Zamanakou, Gedeon Loules, Dorottya Csuka, Fotis Psarros, Faidra Parsopoulou, Matthaios Speletas, Davide Firinu, Tiziana Maria Angela De Pasquale, Alessandra Zoli, Anna Radice, Stefano Pizzimenti, Emmanouil Manoussakis, George N. Konstantinou, Valeria Bafunno, Vincenzo Montinaro, Mauro Cancian, Maurizio Margaglione, Konrad Bork, Karin Wulff, Guenther Witzke, Jochen Hardt, Laurence Bouillet, Teresa Caballero, Anete S. Grumach, Christelle Pommie, Irmgard Andresen, Carmen Escuriola Ettingshausen, Zeynep Gutowski, Karin Andritschke, Richard Linde, Noémi Andrási, Tamás Szilágyi, Iris Leibovich-Nassi, Christine Symons, John Dempster, Isabelle Boccon-Gibod, Anne Pagnier, Audrey Lehmann, Kristian B. Kreiberg, Sandra A. Nieto, Raquel Martins, Renata Martins, Alejandra Menendez, Solange O. R. Valle, Margarita Olivares, Maria E. Hernandez-Landeros, Elma Nievas, Natalia Fili, Olga M. Barrera, René Bailleau, Ana Maria Gallardo-Olivos, Masumi Grau, Julian Rodriguez-Galindo, Marlon J. O. Carabantes, Edison Zapata-Venegas, Mario Martinez Alfonso, Maria Rosario-Grauert, Manuel Ratti, Daniel Vaszquez, Dario Josviack, Luis Fernando Landivar-Salinas, Oscar M. E. Calderón-Llosa, Rolando Campilay-Sarmiento, Pablo Raby, Jose Fabiani, William R. Lumry, Henrike Feuersenger, Douglas J. Watson, Thomas Machnig, on behalf of the Investigators of the COMPACT study, Donatella Lamacchia, Adriana Hernanz, Ana Alvez, Mariana Lluncor, Maria Pedrosa, Rosario Cabañas, Nieves Prior, Patrik Nordenfelt, Mats Nilsson, Anders Lindfors, Carl-Fredrik Wahlgren, Janne Björkander, Roman Hakl, Pavel Kuklínek, Irena Krčmová, Jana Hanzlíková, Martina Vachová, Radana Zachová, Marta Sobotková, Jana Strenková, Jiří Litzman, Maria Palasopoulou, Gerasimina Tsinti, Panagiota Gianni, Maria Kompoti, Sofia Garrido, Wojciech Dyga, Anna Bogdali, Aleksander Obtułowicz, Mikolajczyk Tomasz, Ewa Czarnobilska, Krystyna Obtulowicz, Teofila Książek, Anna Koncz, Dominik Gulyás, Maria Staevska, Milos Jesenak, Katarina Hrubiskova, L. Bellizzi, A. Relan, Maddalena A. Wu, Antonio Castelli, Riccardo Colombo, Gianmarco Podda, Marta Del Medico, Emanuele Catena, Francesco Casella, Francesca Perego, Nada Afifi Afifi, Eleonora Tobaldini, Nicola Montano, for the IOS Study Group, Marta Sánchez-Jareño, Marcin Stobiecki, Krystyna Obtułowicz, Irina Guryanova, Ekaterina Polyakova, Viktar Lebedz, Andrej Salivonchik, Svetlana Aleshkevich, Mikhail Belevtsev, Melanie Nordmann-Kleiner, Susanne Trainotti, Janina Hahn, Jens Greve, Liudmyla Zabrodska, Maria L. Oliva Alonso, Rosangela P. Tórtora, Alfeu T. França, Marcia G. Ribeiro, Lisa Fu, Amin Kanani, Gina Lacuesta, Susan Waserman, Stephen Betschel, Melissa I. Espinosa, Francisco A. Contreras, Martin Hrubisko, Ludmila Vavrova, Peter Banovcin, Maryam Ayazi, Mohammad Reza Fazlollahi, Shiva Saghafi, Sajedeh Mohammadian, Susan Nabilou Deshiry, Kiana Bidad, Raheleh Shokouhi Shoormasti, Iraj Mohammadzadeh, Mohammad Hassan Bemanian, Seyed Alireza Mahdaviani, Zahra Pourpak, Anna Valerieva, Mariela Vasileva, Tsvetelina Velikova, Elena Petkova, Vasil Dimitrov, Ruggero Di Maulo, on behalf of participating centers, Raz Somech, Hava Golander, Erika J. Sifuentes, Catherine Mansard, Anne Gompel, Bernard Floccard, Claire Blanchard-Delaunay, David Launay, Olivier Fain, Alain Sobel, Stéphane Gayet, Stéphanie Amarger, Guillaume Armengol, Yann Ollivier, Ariane Zélinsky-Gurung, Pierre-Yves Jeandel, Gisèle Kanny, Brigitte Coppéré, Marie Dubrel, Fabien Pelletier, Aurélie Du Thanh, Sébastien Trouiller, Jérôme Laurent, Claire De Moreuil, Christine Audouin Pajot, Alexandre Belot, Ana Rodríguez, Dasha Roa, Alicia Prieto, Maria Luisa Baeza, Borislava Krusheva, Stephanie K. A. Almeida, Rosemeire N. Constantino-Silva, Nyla Melo, Joanna Araujo Simoes, Sandra Mitie U. Palma, Jane da Silva, Bruna F. de Azevedo, Eli Mansour, Teresa González-Quevedo, Carmen Marcos, Teófilo Lobera, Blanca Sáenz de San Pedro, Ernie Avilla, Jacquie Badiou, Karen Binkley, Rozita Borici-Mazi, Linda Howlett, Paul K. Keith, Anne Rowe, Peter Waite, Aurore Billebeau, Isabelle Boccon-Gibbod, Kristina Lis, Yael Laitman, Eitan Friedman, N. M. Gokmen, O. Gulbahar, H. Onay, Z. P. Koc, and A. Z. Sin

Subjects
Immunologic diseases. Allergy, RC581-607
Published
2017
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33. Low-dose Btk inhibitors selectively block platelet activation by CLEC-2

Author

Phillip L.R. Nicolson, Sophie H. Nock, Joshua Hinds, Lourdes Garcia-Quintanilla, Christopher W. Smith, Joana Campos, Alexander Brill, Jeremy A. Pike, Abdullah O. Khan, Natalie S. Poulter, Diedre M. Kavanagh, Stephanie Watson, Callum N. Watson, Hayley Clifford, Aarnoud P. Huissoon, Alice Y. Pollitt, Johannes A. Eble, Guy Pratt, Steve P. Watson, and Craig E. Hughes

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Inhibitors of the tyrosine kinase Btk have been proposed as novel antiplatelet agents. In this study we show that low concentrations of the Btk inhibitor ibrutinib block CLEC-2-mediated activation and tyrosine phosphorylation including Syk and PLCγ2 in human platelets. Activation is also blocked in patients with X-linked agammaglobulinemia (XLA) caused by a deficiency or absence of Btk. In contrast, the response to GPVI is delayed in the presence of low concentrations of ibrutinib or in patients with XLA, and tyrosine phosphorylation of Syk is preserved. A similar set of results is seen with the second-generation inhibitor, acalabrutinib. The differential effect of Btk inhibition in CLEC-2 relative to GPVI signalling is explained by the positive feedback role involving Btk itself, as well as ADP and thromboxane A2 mediated activation of P2Y12 and TP receptors, respectively. This feedback role is not seen in mouse platelets and, consistent with this, CLEC-2-mediated activation is blocked by high but not by low concentrations of ibrutinib. Nevertheless, thrombosis was absent in 8 out of 13 mice treated with ibrutinib. These results show that Btk inhibitors selectively block activation of human platelets by CLEC-2 relative to GPVI suggesting that they can be used at 'low dose' in patients to target CLEC-2 in thrombo-inflammatory disease.

Published
2020
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34. Biomarkers in Human Anaphylaxis: A Critical Appraisal of Current Evidence and Perspectives

Author

Sarah C. Beck, Thomas Wilding, Richard J. Buka, Richard L. Baretto, Aarnoud P. Huissoon, and Mamidipudi T. Krishna

Subjects
anaphylaxis, mast cells, tryptase, biomarkers, diagnosis, Immunologic diseases. Allergy, RC581-607
Abstract

Anaphylaxis is a type I hypersensitivity reaction that is potentially fatal if not promptly treated. It is a clinical diagnosis, although measurement of serial serum total mast cell tryptase (MCT) is gold standard and may help differentiate anaphylaxis from its mimics. The performance characteristics of MCT assays in anaphylaxis has been variable in previous studies, due to multiple factors including differences in the definition of anaphylaxis, methods of MCT interpretation, clinical setting of anaphylaxis, causative agents, and timing of blood sample. An international consensus equation for MCT to interpret mast cell activation has been proposed and recently validated in the context of peri-operative anaphylaxis during general anesthesia. There has been an interest in the detection of newer biomarkers in anaphylaxis including platelet activation factor (PAF), chymase, carboxypeptidase A3, dipeptidyl peptidase I (DPPI), basogranulin, and CCL-2. The key determinants of an ideal biomarker in anaphylaxis are half-life, sample handling and processing requirements, and cost. There may be a role for metabolomics and systems biology in the exploration of novel biomarkers in anaphylaxis. Future studies applying these approaches might provide greater insight into factors determining severity, clinical risk stratification, identification of mast cell disorders and improving our understanding of this relatively complex acute immunological condition. Post mortem MCT evaluation is used in Forensic Medicine during autopsy for cases involving sudden death or suspected anaphylaxis. Interpretation of post mortem MCT is challenging since there is limited published evidence and the test is confounded by multiple variables largely linked to putrefaction and site of sampling. Thus, there is no international consensus on a reference range. In this state of the art review, we will focus on the practical challenges in the laboratory diagnosis of anaphylaxis and critically appraise (a) performance characteristics of MCT in anaphylaxis in different clinical scenarios (b) the role for novel biomarkers and (c) post mortem MCT and its role in fatal anaphylaxis.

Published
2019
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35. Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations

Author

Tim Niehues, Catherine Waruiru, Conleth Feighery, Uwe Schauer, Virginie Courteille, Kai Lehmberg, Ingo Müller, I. Esteves, Henner Morbach, Michael Borte, Patrick Hundsdoerfer, Klaus Schwarz, Ewelina Gowin, Alessandro Aiuti, Andreas Holbro, Federica Barzaghi, João Farela Neves, Dagmar Graf, Hannah Tamary, Veneta Milenova, Benedikt Boetticher, Eleonora Gambineri, Vera Goda, Alia Eldash, Jan-Christian Wasmuth, Fabio Candotti, Svetlana O. Sharapova, Markus Metzler, Juergen Brunner, Anna Hilfanova, Brindusa Ruxandra Capilna, Pere Soler-Palacín, Arnau Antolí, Horst von Bernuth, Vassilios Lougaris, Maria Carrabba, Bernd H. Belohradsky, Julian Thalhammer, Nathalie de Vergnes, Peter Olbrich, Peter Kopač, Leif G. Hanitsch, Alexandra Nieters, Filomeen Haerynck, Juliana Gabzdilova, Sezin Aydemir, Rabab El Hawary, Patrick F.K. Yong, Maria Giovanna Danieli, Alberto Tommasini, Sandra Steinmann, Ulrich Baumann, Figen Dogu, Elisabeth Förster-Waldl, Carolina Marasco, Donato Amodio, Lorenzo Lodi, Xavier Solanich, Caterina Cancrini, Brigita Sitkauskiene, Torsten Witte, Clementina Vanessa, Nima Rezaei, Jean-Christophe Goffard, Kirsten Wittke, Emmanouil Liatsis, Helen Baxendale, Susana L. Silva, Bodo Grimbacher, Henrike Ritterbusch, Evangelia Farmaki, Safa Meshaal, Sujal Ghosh, Larysa Kostyuchenko, David Edgar, Simone Cesaro, R Zeuner, Nerea Salmón Rodríguez, Isabella Quinti, Stephan Ehl, Pauline Brosselin, Joerg C. Henes, Pilar Llobet Agulló, Rosa Maria Dellepiane, Andrea Meinhardt, Marina Kojić, Georgios Sogkas, Stephan Borte, Catharina Schuetz, Suheyla Ocak, Karin Marschall, Lukas M. Gasteiger, Stefan Raffac, Sofia Tantou, Sadia Noorani, Matthaios Speletas, Philippe Randrianomenjanahary, Ursula Holzer, Ayca Kiykim, Johannes G. Liese, Angelo Vacca, Gisela Fecker, Ekrem Unal, Koen J. van Aerde, Alba Parra-Martínez, Kaan Boztug, Sophie Stiehler, Sybille Landwehr-Kenzel, Claudio Pignata, Jennifer Neubert, Janine Reichenbach, Shahnaz Parvin, Sarah Goddard, Andrea Schroll, Dirk Holzinger, Asghar Aghamohammadi, Hassan Abolhassani, Johannes Trück, Estela Paz-Artal, Shereen M. Reda, Anna Shcherbina, Maria Raptaki, Jaroslava Orosova, Beata Wolska-Kuśnierz, Tessa Kerre, Gerrit Ahrenstorf, Ben Zion Garty, Dirk Foell, Benjamin Becker, Ulrike F. Demel, Androniki Kapousouzi, Abraham Rutgers, Klaus Warnatz, Gemma Rocamora Blanch, Stephan Rusch, Luis M. Allende, Dalia Abd Elaziz, Safa Baris, Jorisvan Montfrans, Dominik T. Schneider, Raphael Scheible, Juana Gil-Herrera, Gerhard Kindle, Annarosa Soresina, Giovanna Fabio, Uwe Wintergerst, Emilia Faria, Maria Fasshauer, Silvia Ricci, Aisha Elmarsafy, Barbara Pietrucha, Carsten Speckmann, Nizar Mahlaoui, Ulrich Heininger, Isabelle Meyts, Matthew Buckland, Efimia Papadopoulou-Alataki, Robin Kobbe, A Herwadkar, Sebastian F. N. Bode, Ali Sobh, László Maródi, Baldassarre Martire, Chiara Azzari, Maximilian Heeg, Katja Masjosthusmann, Michael H. Albert, Matteo Chinello, Juan Luis Santos-Pérez, Aarnoud Huissoon, Tanya I. Coulter, Hendrik Schulze-Koops, Norbert Graf, Radwa Alkady, Jolanta Bernatoniene, Seraina Prader, Alenka Gagro, Joachim Roesler, Taco W. Kuijpers, Ewa Więsik-Szewczyk, Maria Elena Maccari, Conrad Ferdinand Lippert, Miriam González-Amores, Johannes Dirks, Daniel E Pleguezuelo, Christof M. Kramm, Anders Fasth, Volker Schuster, Olov Ekwall, Nikolaus Rieber, Javier Carbone, Petra Kaiser-Labusch, Diana Ernst, Lucia Augusta Baselli, Luis Ignacio Gonzalez-Granado, Maria Kanariou, Stefanie S. V. Henriet, Sigune Goldacker, Kerstin Felgentreff, Oana Joean, Fine Roosens, Fabian Hauck, Eva C. Schwaneck, Milos Jesenak, Manfred Hoenig, Lenka Kapustova, Christoph Boesecke, Alain Fischer, Sara Pereira da Silva, Julia Körholz, Ansgar Schulz, Carolynne Schwarze-Zander, Mikko Seppänen, Nermeen Galal, Nora Naumann-Bartsch, Tomaz Garcez, Peter Ciznar, Klara M. Posfay-Barbe, Zelimir Pavle Eric, Reinhold E. Schmidt, Hermann J. Girschick, Sabine Heine, Anika-Kerstin Biegner, Annick A. J. M. van de Ven, Stefan Schreiber, J. Merlijn van den Berg, Nurit Assia Batzir, Alexandra Jablonka, Kim Stol, Gregor Dückers, Antonios G.A. Kolios, Ioannis Kakkas, Christian Klemann, Marina N. Guseva, Sofia Grigoriadou, Elif Karakoc-Aydiner, Antonio Marzollo, Peter D. Arkwright, Urs C. Steiner, Sara Sebnem Kilic, Romina Dieli-Crimi, Gergely Kriván, Monika Sparber-Sauer, Marco Cazzaniga, Fulvio Porta, Paraskevi Maggina, Tomas Milota, Robbert G. M. Bredius, Martine Pergent, Klaus Tenbrock, Jana Pachlopnik Schmid, Florentia Dimitriou, Cathal Laurence Steele, Helen Bourne, Anna Bobcakova, Gerd Horneff, Judith Potjewijd, Marc Schmalzing, Tobias Ankermann, Paul Ryan, Oksana Boyarchuk, Necil Kutukculer, Carl Friedrich Classen, Zita Chovancová, Moira Thomas, Cinzia Milito, Michaela Bitzenhofer-Grüber, Faranaz Atschekzei, Eva Hlaváčková, Viviana Moschese, Julie Smet, Hans-Hartmut Peter, Carla Teixeira, Sabine M El-Helou, Suzanne de Kruijf Bazen, Helmut Wittkowski, Donate Jakoby, Marina Garcia-Prat, Esther de Vries, Richard Herriot, Sven Kracker, Alessandro Plebani, Lisa Göschl, Laura Hora Marques, Anna Sediva, Jiri Litzman, Mark M. Gompels, Renate Krüger, Şefika İlknur Kökçü Karadağ, Nadine Binder, Anna Szaflarska, Peter Jandus, Lisa Ibberson, Johann Greil, Ulf Schulze-Sturm, Mehtap Sirin, Aydan Ikinciogullari, Edyta Heropolitańska-Pliszka, Michael E. Weiss, Alla Skapenko, Lukas Wisgrill, Hana Alachkar, Uta Behrends, Silvia Sánchez-Ramón, Maria N. Hatzistilianou, Otilia Petrovicova, Darko Richter, Zoreh Nademi, Jürgen K. Rockstroh, Sohilla Lotfy, Markus G. Seidel, Timothy Ronan Leahy, Audra Blažienė, Translational Immunology Groningen (TRIGR), Paediatric Infectious Diseases / Rheumatology / Immunology, AII - Inflammatory diseases, ARD - Amsterdam Reproduction and Development, University of Zurich, Ehl, Stephan, Thalhammer, J., Kindle, G., Nieters, A., Rusch, S., Seppanen, M. R. J., Fischer, A., Grimbacher, B., Edgar, D., Buckland, M., Mahlaoui, N., Ehl, S., Boztug, K., Brunner, J., Demel, U. F., Forster-Waldl, E., Gasteiger, L. M., Goschl, L., Kojic, M., Schroll, A., Seidel, M. G., Wintergerst, U., Wisgrill, L., Sharapova, S. O., Goffard, J. -C., Kerre, T., Meyts, I., Roosens, F., Smet, J., Haerynck, F., Eric, Z. P., Milenova, V., Gagro, A., Richter, D., Chovancova, Z., Hlavackova, E., Litzman, J., Milota, T., Sediva, A., Elaziz, D. A., Alkady, R. S., El Sayed El Hawary, R., Eldash, A. S., Galal, N., Lotfy, S., Meshaal, S. S., Reda, S. M., Sobh, A., Elmarsafy, A., Brosselin, P., Courteille, V., De Vergnes, N., Kracker, S., Pergent, M., Randrianomenjanahary, P., Ahrenstorf, G., Albert, M. H., Ankermann, T., Atschekzei, F., Baumann, U., Becker, B. C., Behrends, U., Belohradsky, B. H., Biegner, A. -K., Binder, N., Bode, S. F. N., Boesecke, C., Boetticher, B., Borte, M., Borte, S., Classen, C. F., Dirks, J., Duckers, G., El-Helou, S., Ernst, D., Fasshauer, M., Fecker, G., Felgentreff, K., Foell, D., Ghosh, S., Girschick, H. J., Goldacker, S., Graf, N., Graf, D., Greil, J., Hanitsch, L. G., Hauck, F., Heeg, M., Heine, S. I., Henes, J. C., Hoenig, M., Holzer, U., Holzinger, D., Horneff, G., Hundsdoerfer, P., Jablonka, A., Jakoby, D., Joean, O., Kaiser-Labusch, P., Klemann, C., Kobbe, R., Korholz, J., Kramm, C. M., Kruger, R., Landwehr-Kenzel, S., Lehmberg, K., Liese, J. G., Lippert, C. F., Maccari, M. E., Masjosthusmann, K., Meinhardt, A., Metzler, M., Morbach, H., Muller, I., Naumann-Bartsch, N., Neubert, J., Niehues, T., Peter, H. -H., Rieber, N., Ritterbusch, H., Rockstroh, J. K., Roesler, J., Schauer, U., Scheible, R., Schmalzing, M., Schmidt, R. E., Schneider, D. T., Schreiber, S., Schuetz, C., Schulz, A., Schulze-Koops, H., Schulze-Sturm, U., Schuster, V., Schwaneck, E. C., Schwarz, K., Schwarze-Zander, C., Sirin, M., Skapenko, A., Sogkas, G., Sparber-Sauer, M., Speckmann, C., Steinmann, S., Stiehler, S., Tenbrock, K., von Bernuth, H., Warnatz, K., Wasmuth, J. -C., Weiss, M., Witte, T., Wittke, K., Wittkowski, H., Zeuner, R. A., Farmaki, E., Hatzistilianou, M. N., Kakkas, I., Kanariou, M. G., Kapousouzi, A., Liatsis, E., Maggina, P., Papadopoulou-Alataki, E., Raptaki, M., Speletas, M., Tantou, S., Goda, V., Krivan, G., Marodi, L., Abolhassani, H., Aghamohammadi, A., Rezaei, N., Feighery, C., Leahy, T. R., Ryan, P., Batzir, N. A., Garty, B. Z., Tamary, H., Aiuti, A., Amodio, D., Azzari, C., Barzaghi, F., Baselli, L. A., Cancrini, C., Carrabba, M., Cazzaniga, M., Cesaro, S., Chinello, M., Danieli, M. G., Dellepiane, R. M., Fabio, G., Gambineri, E., Lodi, L., Lougaris, V., Marasco, C., Martire, B., Marzollo, A., Milito, C., Moschese, V., Pignata, C., Plebani, A., Porta, F., Quinti, I., Ricci, S., Soresina, A., Tommasini, A., Vacca, A., Vanessa, C., Blaziene, A., Sitkauskiene, B., Gowin, E., Heropolitanska-Pliszka, E., Pietrucha, B., Szaflarska, A., Wiesik-Szewczyk, E., Wolska-Kusnierz, B., Esteves, I., Faria, E., Marques, L. H., Neves, J. F., Silva, S. L., Teixeira, C., Pereira da Silva, S., Capilna, B. R., Guseva, M. N., Shcherbina, A., Bobcakova, A., Ciznar, P., Gabzdilova, J., Jesenak, M., Kapustova, L., Orosova, J., Petrovicova, O., Raffac, S., Kopac, P., Allende, L. M., Antoli, A., Blanch, G. R., Carbone, J., Dieli-Crimi, R., Garcia-Prat, M., Gil-Herrera, J., Gonzalez-Granado, L. I., Agullo, P. L., Olbrich, P., Parra-Martinez, A., Paz-Artal, E., Pleguezuelo, D. E., Rodriguez, N. S., Sanchez-Ramon, S., Santos-Perez, J. L., Solanich, X., Soler-Palacin, P., Gonzalez-Amores, M., Ekwall, O., Fasth, A., Bitzenhofer-Gruber, M., Candotti, F., Dimitriou, F., Heininger, U., Holbro, A., Jandus, P., Kolios, A. G. A., Marschall, K., Schmid, J. P., Posfay-Barbe, K. M., Prader, S., Reichenbach, J., Steiner, U. C., Truck, J., Bredius, R. G., de Kruijf- Bazen, S., de Vries, E., Henriet, S. S. V., Kuijpers, T. W., Potjewijd, J., Rutgers, A., Stol, K., van Aerde, K. J., Van den Berg, J. M., van de Ven, A. A. J. M., Montfrans, J., Aydemir, S., Baris, S., Dogu, F., Ikinciogullari, A., Karakoc-Aydiner, E., Kilic, S. S., Kiykim, A., Kokcu Karadag, S. I., Kutukculer, N., Ocak, S., Unal, E., Boyarchuk, O., Hilfanova, A., Kostyuchenko, L. V., Alachkar, H., Arkwright, P. D., Baxendale, H. E., Bernatoniene, J., Coulter, T. I., Garcez, T., Goddard, S., Gompels, M. M., Grigoriadou, S., Herriot, R., Herwadkar, A., Huissoon, A., Ibberson, L., Nademi, Z., Noorani, S., Parvin, S., Steele, C. L., Thomas, M., Waruiru, C., Yong, P. F. K., and Bourne, H.

Subjects
0301 basic medicine, Male, Pediatrics, syndromic, Sex Factor, Disease, registry, medicine.disease_cause, Cohort Studies, 0302 clinical medicine, Primary Immunodeficiency Disease, inborn error of immunity, Immunology and Allergy, warning signs, Age Factor, Registries, Family history, presenting symptom, Child, Primary immunodeficiency, Granuloma, autoimmune, immune dysregulation, inflammatory, Adult, Autoimmune Diseases, Female, Humans, Infections, Lymphoproliferative Disorders, Middle Aged, Primary Immunodeficiency Diseases, Sex Factors, Age Factors, 10177 Dermatology Clinic, Infections/epidemiology, 3. Good health, Settore MED/02, Warning signs, Lymphoproliferative Disorder, 2723 Immunology and Allergy, Infection, Human, medicine.medical_specialty, Immunology, 610 Medicine & health, Malignancy, primary immunodeficiency, Autoimmune Disease, 03 medical and health sciences, Immunity, Autoimmune Diseases/epidemiology, medicine, 2403 Immunology, business.industry, warning sign, Common variable immunodeficiency, Granuloma/epidemiology, Immune dysregulation, medicine.disease, Primary Immunodeficiency Diseases/epidemiology, 030104 developmental biology, Lymphoproliferative Disorders/epidemiology, Cohort Studie, business, 030215 immunology
Abstract

BACKGROUND: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations.OBJECTIVE: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts.METHODS: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered.RESULTS: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years.CONCLUSIONS: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.

Published
2021

39. The efficacy and safety of systemic corticosteroids as first line treatment for granulomatous lymphocytic interstitial lung disease

Author

Immuno/reuma onderzoek 1 (Vastert), Cluster B, Immuno/reuma patientenzorg, Child Health, Infection & Immunity, Smits, Bas, Goldacker, Sigune, Seneviratne, Suranjith, Malphettes, Marion, Longhurst, Hilary, Mohamed, Omar E., Witt-Rautenberg, Carla, Leeman, Lucy, Schwaneck, Eva, Raymond, Isabelle, Meghit, Kilifa, Uhlmann, Annette, Winterhalter, Christine, van Montfrans, Joris, Klima, Marion, Workman, Sarita, Fieschi, Claire, Lorenzo, Lorena, Boyle, Sonja, Onyango-Odera, Shamin, Price, Suzanne, Schmalzing, Marc, Aurillac, Valerie, Prasse, Antje, Hartmann, Ieneke, Meerburg, Jennifer J., Kemner-van de Corput, Mariette, Tiddens, Harm, Grimbacher, Bodo, Kelleher, Peter, Patel, Smita Y., Korganow, Anne Sophie, Viallard, Jean Francois, Tony, Hans Peter, Bethune, Claire, Schulze-Koops, Hendrik, Witte, Torsten, Huissoon, Aarnoud, Baxendale, Helen, Grigoriadou, Sofia, Oksenhendler, Eric, Burns, Siobhan O., Warnatz, Klaus, Immuno/reuma onderzoek 1 (Vastert), Cluster B, Immuno/reuma patientenzorg, Child Health, Infection & Immunity, Smits, Bas, Goldacker, Sigune, Seneviratne, Suranjith, Malphettes, Marion, Longhurst, Hilary, Mohamed, Omar E., Witt-Rautenberg, Carla, Leeman, Lucy, Schwaneck, Eva, Raymond, Isabelle, Meghit, Kilifa, Uhlmann, Annette, Winterhalter, Christine, van Montfrans, Joris, Klima, Marion, Workman, Sarita, Fieschi, Claire, Lorenzo, Lorena, Boyle, Sonja, Onyango-Odera, Shamin, Price, Suzanne, Schmalzing, Marc, Aurillac, Valerie, Prasse, Antje, Hartmann, Ieneke, Meerburg, Jennifer J., Kemner-van de Corput, Mariette, Tiddens, Harm, Grimbacher, Bodo, Kelleher, Peter, Patel, Smita Y., Korganow, Anne Sophie, Viallard, Jean Francois, Tony, Hans Peter, Bethune, Claire, Schulze-Koops, Hendrik, Witte, Torsten, Huissoon, Aarnoud, Baxendale, Helen, Grigoriadou, Sofia, Oksenhendler, Eric, Burns, Siobhan O., and Warnatz, Klaus

Published
2023

40. Case report: Clearance of longstanding, immune-deficiency-associated, vaccine-derived polio virus infection following remdesivir therapy for chronic SARS-CoV-2 infection

Author

Bermingham, William Hywel, primary, Canning, Benjamin, additional, Wilton, Thomas, additional, Kidd, Michael, additional, Klapsa, Dimitra, additional, Majumdar, Manasi, additional, Sooriyakumar, Kavitha, additional, Martin, Javier, additional, and Huissoon, Aarnoud P., additional

Published
2023
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41. Outcomes following SARS-CoV-2 infection in patients with primary and secondary immunodeficiency in the UK

Author

Katie Townsend, Evon Boules, Rachael O’Brien, Sai Murng, Smita Y. Patel, Helen Baxendale, Siraj A. Misbah, Ariharan Anantharachagan, Aarnoud Huissoon, Richard Herriot, Andrew R. Gennery, Kenneth F Baker, David M. Lowe, Lucy Leeman, Suzanne Elcombe, Alex G. Richter, Grant Hayman, Philip D Bright, Moira Thomas, Sarah Goddard, Magdalena Dziadzio, Prashantha M. Vaitla, Sameer Bahal, Betsy Cleave, Dylan James Mac Lochlainn, Elizabeth McDermott, Malini Bhole, Anna Shrimpton, Sujoy Khan, Nisha Verma, William H. Bermingham, Sinisa Savic, Anthony Williams, Gururaj Arumugakani, Lavanya Diwakar, Elizabeth Drewe, James Laffan, Lucy Cliffe, Catherine Stroud, Stephen Jolles, A Herwadkar, Siobhan O. Burns, Adrian M Shields, Shanti Mahabir, Scott Hackett, Sofia Grigoriadou, Sarah Johnston, John Dempster, Hadeil Morsi, Peter Lane, Sadia Noorani, Arthur Price, Tasneem Rahman, Fatima Dhalla, Christopher J A Duncan, Lisa Devlin, Harichandrana Ghanta, Fiona Moghaddas, Charu Chopra, Suranjith Senevirantne, Shuayb Elkhalifa, and Rashmi Jain

Subjects
medicine.medical_specialty, inborn errors of immunity, hypogammaglobulinemia, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, AcademicSubjects/MED00730, secondary immunodeficiencies, Antibodies, Monoclonal, Humanized, Antibodies, Viral, Dexamethasone, Secondary immunodeficiency, AcademicSubjects/MED00160, Internal medicine, Medicine, Immunology and Allergy, Humans, In patient, COVID-19 Serotherapy, business.industry, SARS-CoV-2, Immunization, Passive, Immunologic Deficiency Syndromes, COVID-19, lymphopenia, Antibodies, Neutralizing, United Kingdom, COVID-19 Drug Treatment, Drug Combinations, business, AcademicSubjects/MED00010, AcademicSubjects/MED00690, Research Article, primary immunodeficiencies
Abstract

Purpose To define the burden of morbidity and mortality arising from COVID-19 in individuals with primary (PID) and secondary immunodeficiency (SID) in the United Kingdom. Methods In March 2020, the United Kingdom Primary Immunodeficiency Network (UKPIN) established a registry of cases to collate the outcomes of individuals with PID and SID following SARS-CoV-2 infection and treatment. Anonymised demographic data, pre-SARS-CoV-2 infection lymphocyte counts, co-morbidities, targeted treatments and outcomes were collected. Three groups were analysed in further detail: individuals with common variable immunodeficiency (CVID), individuals with any PID, including CVID, receiving immunoglobulin replacement therapy (IgRT) and individuals with secondary immunodeficiency. Results A total of 310 cases of SARS-CoV-2 infection in individuals with PID or SID have now been reported in the UK. The overall mortality within the cohort was 17.7% (n = 55/310). Individuals with CVID demonstrated an infection fatality rate (IFR) of 18.3% (n = 17/93), individuals with PID receiving IgRT had an IFR of 16.3% (n = 26/159) and individuals with SID, an IFR of 27.2% (n = 25/92). Individuals with PID and SID, had higher inpatient mortality and died at a younger age than the general population. Increasing age, low pre-SARS-CoV-2 infection lymphocyte count and the presence of common co-morbidities increased the risk of mortality in PID. Access to specific COVID-19 treatments in this cohort was limited: only 22.9% (n = 33/144) of patients admitted to hospital received dexamethasone, remdesivir, an anti-SARS-CoV-2 antibody-based therapeutic (e.g. REGN-COV2 or convalescent plasma) or tocilizumab as a monotherapy or in combination. Dexamethasone, remdesivir and anti-SARS-CoV-2 antibody-based therapeutics appeared efficacious in PID and SID. Conclusion Compared to the general population, individuals with PID or SID are at high risk of mortality following SARS-CoV-2 infection. Increasing age, low baseline lymphocyte count and the presence of co-morbidities are additional risk factors for poor outcome in this cohort.

Published
2023

45. Inhibition of Btk by Btk-specific concentrations of ibrutinib and acalabrutinib delays but does not block platelet aggregation mediated by glycoprotein VI

Author

Phillip L.R. Nicolson, Craig E. Hughes, Stephanie Watson, Sophie H. Nock, Alexander T. Hardy, Callum N. Watson, Samantha J. Montague, Hayley Clifford, Aarnoud P. Huissoon, Jean-Daniel Malcor, Mark R. Thomas, Alice Y. Pollitt, Michael G. Tomlinson, Guy Pratt, and Steve P. Watson

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Ibrutinib and acalabrutinib are irreversible inhibitors of Bruton tyrosine kinase used in the treatment of B-cell malignancies. They bind irreversibly to cysteine 481 of Bruton tyrosine kinase, blocking autophosphorylation on tyrosine 223 and phosphorylation of downstream substrates including phospholipase C-γ2. In the present study, we demonstrate that concentrations of ibrutinib and acalabrutinib that block Bruton tyrosine kinase activity, as shown by loss of phosphorylation at tyrosine 223 and phospholipase C-γ2, delay but do not block aggregation in response to a maximally-effective concentration of collagen-related peptide or collagen. In contrast, 10- to 20-fold higher concentrations of ibrutinib or acalabrutinib block platelet aggregation in response to glycoprotein VI agonists. Ex vivo studies on patients treated with ibrutinib, but not acalabrutinib, showed a reduction of platelet aggregation in response to collagen-related peptide indicating that the clinical dose of ibrutinib but not acalabrutinib is supramaximal for Bruton tyrosine kinase blockade. Unexpectedly, low concentrations of ibrutinib inhibited aggregation in response to collagen-related peptide in patients deficient in Bruton tyrosine kinase. The increased bleeding seen with ibrutinib over acalabrutinib is due to off-target actions of ibrutinib that occur because of unfavorable pharmacodynamics.

Published
2018
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50. Thermal Dynamic Modeling and Control of Injection Moulding Process

Author

Seo, Jaho, Khajepour, Amir, Huissoon, Jan P., Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Nierstrasz, Oscar, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Sudan, Madhu, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Vardi, Moshe Y., Series editor, Weikum, Gerhard, Series editor, Goebel, Randy, editor, Siekmann, Jörg, editor, Wahlster, Wolfgang, editor, Kamel, Mohamed, editor, Karray, Fakhri, editor, Gueaieb, Wail, editor, and Khamis, Alaa, editor

Published
2011
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