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1. Targeting NF-κB signaling in B cells as a potential new treatment modality for ANCA-associated vasculitis

Author

Merino-Vico, Ana, van Hamburg, Jan Piet, Tuijnenburg, Paul, Frazzei, Giulia, Al-Soudi, Aram, Bonasia, Carlo G., Helder, Boy, Rutgers, Abraham, Abdulahad, Wayel H., Stegeman, Coen A., Sanders, Jan-Stephan, Bergamaschi, Laura, Lyons, Paul A., Bijma, Theo, van Keep, Laura, Wesenhagen, Kirsten, Jongejan, Aldo, Olsson, Henric, de Vries, Niek, Kuijpers, Taco W., Heeringa, Peter, and Tas, Sander W.

Published
2024
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2. 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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3. 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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4. The TNF Receptor Superfamily-NF-κB Axis Is Critical to Maintain Effector Regulatory T Cells in Lymphoid and Non-lymphoid Tissues

Author

Vasanthakumar, Ajithkumar, Liao, Yang, Teh, Peggy, Pascutti, Maria F., Oja, Anna E., Garnham, Alexandra L., Gloury, Renee, Tempany, Jessica C., Sidwell, Tom, Cuadrado, Eloy, Tuijnenburg, Paul, Kuijpers, Taco W., Lalaoui, Najoua, Mielke, Lisa A., Bryant, Vanessa L., Hodgkin, Philip D., Silke, John, Smyth, Gordon K., Nolte, Martijn A., Shi, Wei, and Kallies, Axel

Published
2017
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5. Mutations in EXTL3 Cause Neuro-immuno-skeletal Dysplasia Syndrome

Author

Oud, Machteld M., Tuijnenburg, Paul, Hempel, Maja, van Vlies, Naomi, Ren, Zemin, Ferdinandusse, Sacha, Jansen, Machiel H., Santer, René, Johannsen, Jessika, Bacchelli, Chiara, Alders, Marielle, Li, Rui, Davies, Rosalind, Dupuis, Lucie, Cale, Catherine M., Wanders, Ronald J.A., Pals, Steven T., Ocaka, Louise, James, Chela, Müller, Ingo, Lehmberg, Kai, Strom, Tim, Engels, Hartmut, Williams, Hywel J., Beales, Phil, Roepman, Ronald, Dias, Patricia, Brunner, Han G., Cobben, Jan-Maarten, Hall, Christine, Hartley, Taila, Le Quesne Stabej, Polona, Mendoza-Londono, Roberto, Davies, E. Graham, de Sousa, Sérgio B., Lessel, Davor, Arts, Heleen H., and Kuijpers, Taco W.

Published
2017
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6. Publisher Correction:Whole-genome sequencing of a sporadic primary immunodeficiency cohort (Nature, (2020), 583, 7814, (90-95), 10.1038/s41586-020-2265-1)

Author

Thaventhiran, James E.D., Lango Allen, Hana, Burren, Oliver S., Rae, William, Greene, Daniel, Staples, Emily, Zhang, Zinan, Farmery, James H.R., Simeoni, Ilenia, Rivers, Elizabeth, Maimaris, Jesmeen, Penkett, Christopher J., Stephens, Jonathan, Deevi, Sri V.V., Sanchis-Juan, Alba, Gleadall, Nicholas S., Thomas, Moira J., Sargur, Ravishankar B., Gordins, Pavels, Baxendale, Helen E., Brown, Matthew, Tuijnenburg, Paul, Worth, Austen, Hanson, Steven, Linger, Rachel J., Buckland, Matthew S., Rayner-Matthews, Paula J., Gilmour, Kimberly C., Samarghitean, Crina, Seneviratne, Suranjith L., Sansom, David M., Lynch, Andy G., Megy, Karyn, Ellinghaus, Eva, Ellinghaus, David, Jorgensen, Silje F., Karlsen, Tom H., Stirrups, Kathleen E., Cutler, Antony J., Kumararatne, Dinakantha S., Chandra, Anita, Edgar, J. David M., Herwadkar, Archana, Cooper, Nichola, Grigoriadou, Sofia, Huissoon, Aarnoud P., Goddard, Sarah, Jolles, Stephen, Schuetz, Catharina, Boschann, Felix, Abbs, Stephen, Adhya, Zoe, Adlard, Julian, Afzal, Maryam, Ahmed, Irshad, Ahmed, Munaza, Ahmed, Saeed, Aitman, Timothy J., Alachkar, Hana, Alamelu, Jayanthi, Alikhan, Raza, Allen, Carl E., Allen, Louise, Allsup, David J., Alvi, Arif, Ambegaonkar, Gautam, Anantharachagan, Ariharan, Ancliff, Philip, Anderson, Julie, Antrobus, Richard, Armstrong, Ruth, Arno, Gavin, Arumugakani, Gururaj, Arya, Rita, Ashford, Sofie, Astle, William J., Attwood, Anthony, Austin, Steve, Aydinok, Yesim, Ayub, Waqar, Babbs, Christian, Bacchelli, Chiara, Baglin, Trevor, Bakchoul, Tamam, Bariana, Tadbir K., Barratt, Jonathan, Barwell, Julian, Baski, John, Bates, Rachel W., Batista, Joana, Baynam, Gareth, Bennett, David L., Bethune, Claire, Bhatnagar, Neha, Bibi, Shahnaz, Bierzynska, Agnieszka, Biss, Tina, Bitner-Glindzicz, Maria A.K., Bleda, Marta, Blesneac, Iulia, Boardman, Barbara, Boddana, Preetham, Bogaard, Harm J., Booth, Claire, Boyce, Sara, Bradley, John R., Brady, Angela, Breen, Gerome, Brennan, Paul, Brewer, Carole, Briley, Annette, Brown, Richard, Browning, Michael J., Brownlie, Mary, Bryson, Christine J., Buchan, Rachel J., Buck, Jackie, Bueser, Teofila, Diz, Carmen Bugarin, Burns, Siobhan O., Calleja, Paul, Carmichael, Jenny, Carr-White, Gerald, Carss, Keren J., Casey, Ruth, Chalmers, Elizabeth, Chambers, Jenny, Chambers, John, Chan, Melanie M.Y., Chan, Melissa V., Cheng, Floria, Chinn, Ivan K., Chinnery, Patrick F., Chitre, Manali, Chong, Sam, Christian, Martin T., Church, Colin, Clement, Emma M., Brod, Naomi Clements, Clifford, Hayley, Clowes, Virginia E., Coghlan, Gerry, Colby, Elizabeth, Cole, Trevor R.P., Collins, Janine H., Collins, Peter W., Condliffe, Robin, Cook, H. Terence, Cook, Stuart, Cookson, Victoria, Corris, Paul A., Creaser-Myers, Amanda, Crisp-Hihn, Abigail, Curry, Nicola S., Da Costa, Rosa, Danesino, Cesare, Daniels, Matthew J., Darby, Damaris, Daugherty, Louise C., Davies, E. G., Davies, Sophie, Davis, John, de Bree, Godelieve J., Deacock, Sarah, Deegan, Patrick B., Dempster, John, Dent, Timothy, Deshpande, Charu, Devlin, Lisa A., Dewhurst, Eleanor F., Dixit, Anand K., Dixon, Peter H., Doffinger, Rainer, Dolling, Helen, Dormand, Natalie, Downes, Kate, Drazyk, Anna M., Drewe, Elizabeth, Duarte, Daniel, Dutt, Tina, Edwards, Karen E., Egner, William, Ekani, Melanie N., El-Shanawany, Tariq, Elkhalifa, Shuayb, Elston, Tony, Emmerson, Ingrid, Erber, Wendy N., Erwood, Marie, Estiu, Maria C., Evans, Dafydd Gareth, Evans, Gillian, Everington, Tamara, Eyries, Mélanie, Favier, Remi, Firth, Helen V., Fitzpatrick, Maggie M., Fletcher, Debra, Flinter, Frances A., Fox, James C., Frary, Amy J., French, Courtney E., Freson, Kathleen, Frontini, Mattia, Furie, Bruce, Gale, Daniel P., Gall, Henning J., Gardham, Alice, Gaspar, H. Bobby, Gattens, Michael, Ghali, Neeti, Ghataorhe, Pavandeep K., Ghio, Stefano, Ghofrani, Hossein Ardeschir, Ghurye, Rohit, Gibbs, J. Simon R., Gilbert, Rodney D., Girerd, Barbara, Girling, Joanna C., Gissen, Paul, Gorman, Kathleen M., Gosal, David, Graf, Stefan, Grassi, Luigi, Greenhalgh, Alan J., Greenhalgh, Lynn, Greinacher, Andreas, Gresele, Paolo, Griffiths, Philip G., Griffiths, Sian, Grozeva, Detelina, Hackett, Scott J., Hadden, Robert D.M., Hadinnapola, Charaka, Hague, Rosie, Hague, William M., Haimel, Matthias, Hall, Matthew, Halmagyi, Csaba, Hammerton, Tracey, Hanson, Helen L., Harkness, Kirsty, Harper, Andrew R., Harper, Lorraine, Harris, Claire, Harrison, Claire, Hart, Daniel, Hassan, Ahamad, Hayman, Grant, Heemskerk, Johan W.M., Hegde, Shivaram, Henderson, Alex, Henderson, Robert H., Hensiek, Anke, Henskens, Yvonne M.C., Hodgson, Joshua, Hoffman, Jonathan, Holden, Simon, Holder, Muriel, Horvath, Rita, Houlden, Henry, Houweling, Arjan C., Howard, Luke S., Hu, Fengyuan, Hudson, Gavin, Hughes, Sean, Hughes, Stephen, Huis in ‘t Veld, Anna E., Humbert, Marc, Hurles, Matthew E., Hurst, Jane A., Irvine, Val, Izatt, Louise, James, Roger, Jeevaratnam, Praveen, Johnson, Mark, Johnson, Sally A., Jolley, Jennifer D., Jones, Bryony, Jones, Julie, Josifova, Dragana, Jurkute, Neringa, Karim, Yousuf M., Karoshi, Mahantesh A., Kasanicki, Mary A., Kazkaz, Hanadi, Kazmi, Rashid, Keeling, David, Kelleher, Peter, Kelly, Anne M., Kempster, Carly, Kennedy, Fiona, Kiani, Sorena, Kiely, David G., Kingston, Nathalie, Kinsey, Sally, Klein, Nigel, Klima, Robert, Knox, Ellen, Kostadima, Myrto A., Kovacs, Gabor, Koziell, Ania B., Kreuzhuber, Roman, Krishnakumar, Deepa, Kuijpers, Taco W., Kumar, Ajith, Kurian, Manju A., Laffan, James, Laffan, Michael A., Lalloo, Fiona, Lambert, Michele P., Lawman, Sarah H.A., Lawrie, Allan, Layton, D. Mark, Lear, Sara E., Lees, Melissa M., Lentaigne, Claire, Levine, Adam P., Lewington, Andrew J.P., Li, Wei, Liesner, Ri, Liu, Bin, Longhurst, Hilary, Lorenzo, Lorena E., Louka, Eleni, Hadeler, Silvia Lucato, Lyons, Paul A., Macdougall, Malcolm, Machado, Rajiv D., MacKenzie Ross, Robert V., Mackillop, Lucy H., MacLaren, Robert, Madan, Bella, Magee, Laura, Mahdi-Rogers, Mohamed, Maher, Eamonn R., Makris, Mike, Mangles, Sarah, Manson, Ania, Manzur, Adnan, Mapeta, Rutendo, Marchbank, Kevin J., Mark, Patrick B., Marks, Stephen, Markus, Hugh S., Marschall, Hanns Ulrich, Marshall, Andrew, Martin, Jennifer M., Masati, Larahmie, Mathias, Mary, Matser, Vera, Matthews, Emma L., Maw, Anna, Maxwell, Heather, McAlinden, Paul, McCarthy, Mark I., McDermott, Elizabeth M., McGowan, Simon J., McJannet, Coleen, McKinney, Harriet, Meacham, Stuart, Mead, Adam J., Castello, Ignacio Medina, Meehan, Sharon, Mehta, Sarju, Mercer, Catherine L., Michaelides, Michel, Michell, Anna C., Milford, David, Millar, Carolyn M., Millar, Hazel, Mistry, Anoop, Moenen, Floor, Moledina, Shahin, Montani, David, Moore, Anthony T., Moore, Jason, Morrell, Nicholas W., Morrisson, Valerie, Mozere, Monika, Muir, Keith W., Mumford, Andrew D., Murng, Sai H.K., Nasir, Iman, Nejentsev, Sergey, Newnham, Michael, Ng, Joanne, Ngoh, Adeline, Noorani, Sadia, Noori, Muna, Nurden, Paquita, O’Sullivan, Jennifer M., Obaji, Samya, Okoli, Steven, Oksenhendler, Eric, Olschewski, Andrea, Olschewski, Horst, Ong, Albert C.M., Ong, Kai Ren, Oram, Helen, Ormondroyd, Elizabeth, Othman, Shokri, Ouwehand, Willem H., Pantazis, Antonis, Papadia, Sofia, Papandreou, Apostolos, Park, Soo Mi, Parker, Alasdair P.J., Parry, David, Parsons, Georgina, Pasi, K. John, Paterson, Joan, Payne, Jeanette H., Peacock, Andrew J., Peerlinck, Kathelijne, Pepke-Zaba, Joanna, Perry, David, Petersen, Romina, Piechowski-Jozwiak, Bartlomiej, Pinto, Fernando, Polwarth, Gary J., Ponsford, Mark J., Prasad, Sanjay, Prokopenko, Inga, Psaila, Beth, Pyle, Angela, Qasim, Waseem, Quinn, Ellen, Quinti, Isabella, Raina, Sanjay, Ranganathan, Lavanya, Rankin, Julia, Rankin, Stuart, Rao, Anupama, Raymond, F. Lucy, Rehnstrom, Karola, Reid, Evan, Reilly, Mary M., Renton, Tara, Revel-Vilk, Shoshana, Rhodes, Christopher J., Rice, Andrew S.C., Richards, Emma E., Richards, Mike, Richardson, Sylvia, Richter, Alex, Robert, Leema, Roberts, Irene, Rondina, Matthew T., Rosser, Elisabeth, Rothwell, Peter, Roughley, Catherine, Roy, Noemi B., Rue-Albrecht, Kevin, Sadeghi-Alavijeh, Omid, Saleem, Moin A., Salmon, Richard M., Samani, Nilesh J., Sambrook, Jennifer G., Sandford, Richard, Santra, Saikat, Satchell, Simon C., Savic, Sinisa, Scelsi, Laura, Schotte, Gwen, Schulman, Sol, Schulze, Harald, Scott, Richard, Scully, Marie, Searle, Claire, Seeger, Werner, Sewell, W. A.Carrock, Seyres, Denis, Shackley, Fiona, Shamardina, Olga, Shapiro, Susan E., Sharma, Pankaj, Shehata, Hassan A., Shipley, Deborah, Shtoyerman, Rakefet, Sibson, Keith, Side, Lucy, Simpson, Michael, Sims, Matthew C., Sinha, Manish D., Sivapalaratnam, Suthesh, Skytte, Anne Bine, Smith, Kenneth G.C., Snape, Katie, Sneddon, Linda, Sohal, Aman, Soubrier, Florent, Southgate, Laura, Southwood, Mark, Splitt, Miranda, Staines, Simon, Stark, Hannah, Stauss, Hans, Steele, Cathal L., Stein, Daniel, Stein, Penelope E., Stock, Sophie, Stubbs, Matthew J., Suntharalingam, Jay, Swietlik, Emilia M., Symington, Emily, Tait, R. Campbell, Talks, Kate, Tan, Rhea Y.Y., Taylor, Gordon B., Thachil, Jecko, Themistocleous, Andreas C., Thomas, David C., Thomas, Ellen, Thomas, Patrick, Thompson, Dorothy A., Thomson, Kate, Thrasher, Adrian J., Thys, Chantal, Tilly, Tobias, Tischkowitz, Marc, Titterton, Catherine, Todd, John A., Toh, Cheng Hock, Tool, Anton T.J., Toshner, Mark R., Traylor, Matthew, Treacy, Carmen M., Treadaway, Paul, Trembath, Richard C., Trippier, Sarah, Tuna, Salih, Turek, Wojciech, Turro, Ernest, Upton, Paul D., Urniaz, Rafal, Vale, Tom, Van Geet, Chris, van Zuydam, Natalie, Vandersteen, Anthony M., Vazquez-Lopez, Marta, Veltman, Marijcke W.M., Vogt, Julie, von Ziegenweidt, Julie, Noordegraaf, Anton Vonk, Vora, Ajay, Vries, Minka J.A., Wakeling, Emma L., Walker, Neil, Walker, Suellen M., Walsh, Roddy, Wanjiku, Ivy, Ware, James S., Warner, Timothy Q., Wassmer, Evangeline, Watkins, Hugh, Watson, Henry G., Watt, Christopher, Waugh, Dean, Webb, Nick, Webster, Andrew R., Wei, Wei, Welch, Angela, Welch, Steven B., Werring, David, Wessels, Julie, Westbury, Sarah K., Westwood, John Paul W., Wharton, John, Whitehorn, Deborah, Whitworth, James, Wilkins, Martin R., Willcocks, Lisa, Williams, David J., Williamson, Catherine, Wong, Edwin K.S., Wood, Nicholas, Wood, Yvette, Woods, Christopher Geoffrey, Woodward, Emma R., Workman, Sarita, Wort, Stephen J., Yates, Katherine, Yeatman, Nigel, Yong, Patrick F.K., Young, Timothy, Yu, Ping, Yu-Wai-Man, Patrick, Zlamalova, Eliska, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, and ACS - Atherosclerosis & ischemic syndromes

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020
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7. Whole-genome sequencing of a sporadic primary immunodeficiency cohort

Author

Thaventhiran, James E. D., Lango Allen, Hana, Burren, Oliver S., Rae, William, Greene, Daniel, Staples, Emily, Zhang, Zinan, Farmery, James H. R., Simeoni, Ilenia, Rivers, Elizabeth, Maimaris, Jesmeen, Penkett, Christopher J., Stephens, Jonathan, Deevi, Sri V. V., Sanchis-Juan, Alba, Gleadall, Nicholas S., Thomas, Moira J., Sargur, Ravishankar B., Gordins, Pavels, Baxendale, Helen E., Brown, Matthew, Tuijnenburg, Paul, Worth, Austen, Hanson, Steven, Linger, Rachel J., Buckland, Matthew S., Rayner-Matthews, Paula J., Gilmour, Kimberly C., Samarghitean, Crina, Seneviratne, Suranjith L., Sansom, David M., Lynch, Andy G., Megy, Karyn, Ellinghaus, Eva, Ellinghaus, David, Jorgensen, Silje F., Karlsen, Tom H., Stirrups, Kathleen E., Cutler, Antony J., Kumararatne, Dinakantha S., Chandra, Anita, Edgar, J. David M., Herwadkar, Archana, Cooper, Nichola, Grigoriadou, Sofia, Huissoon, Aarnoud P., Goddard, Sarah, Jolles, Stephen, Schuetz, Catharina, Boschann, Felix, Lyons, Paul A., Hurles, Matthew E., Savic, Sinisa, Burns, Siobhan O., Kuijpers, Taco W., Turro, Ernest, Ouwehand, Willem H., Thrasher, Adrian J., Smith, Kenneth G. C., Tait, R. Campbell, Chalmers, Elizabeth, Hague, Rosie, Maxwell, Heather, Peacock, Andrew J., Mark, Patrick B., and Muir, Keith W.

Abstract

Primary immunodeficiency (PID) is characterized by recurrent and often life-threatening infections, autoimmunity and cancer, and it poses major diagnostic and therapeutic challenges. Although the most severe forms of PID are identified in early childhood, most patients present in adulthood, typically with no apparent family history and a variable clinical phenotype of widespread immune dysregulation: about 25% of patients have autoimmune disease, allergy is prevalent and up to 10% develop lymphoid malignancies1,2,3. Consequently, in sporadic (or non-familial) PID genetic diagnosis is difficult and the role of genetics is not well defined. Here we address these challenges by performing whole-genome sequencing in a large PID cohort of 1,318 participants. An analysis of the coding regions of the genome in 886 index cases of PID found that disease-causing mutations in known genes that are implicated in monogenic PID occurred in 10.3% of these patients, and a Bayesian approach (BeviMed4) identified multiple new candidate PID-associated genes, including IVNS1ABP. We also examined the noncoding genome, and found deletions in regulatory regions that contribute to disease causation. In addition, we used a genome-wide association study to identify loci that are associated with PID, and found evidence for the colocalization of—and interplay between—novel high-penetrance monogenic variants and common variants (at the PTPN2 and SOCS1 loci). This begins to explain the contribution of common variants to the variable penetrance and phenotypic complexity that are observed in PID. Thus, using a cohort-based whole-genome-sequencing approach in the diagnosis of PID can increase diagnostic yield and further our understanding of the key pathways that influence immune responsiveness in humans.

Published
2020

9. A combined immunodeficiency with severe infections, inflammation, and allergy caused by ARPC1B deficiency

Author

Volpi, Stefano, Cicalese, Maria Pia, Tuijnenburg, Paul, Tool, Anton T.J., Cuadrado, Eloy, Abu-Halaweh, Marwan, Ahanchian, Hamid, Alzyoud, Raed, Akdemir, Zeynep Coban, Barzaghi, Federica, Blank, Alexander, Boisson, Bertrand, Bottino, Cristina, Brigida, Immacolata, Caorsi, Roberta, Casanova, Jean-Laurent, Chiesa, Sabrina, Chinn, Ivan Kingyue, Dückers, Gregor, Enders, Anselm, Erichsen, Hans Christian, Forbes, Lisa R., Gambin, Tomasz, Gattorno, Marco, Karimiani, Ehsan Ghayoor, Giliani, Silvia, Gold, Michael S., Jacobsen, Eva-Maria, Jansen, Machiel H., King, Jovanka R., Laxer, Ronald M., Lupski, James R., Mace, Emily, Marcenaro, Stefania, Maroofian, Reza, Meijer, Alexander B., Niehues, Tim, Notarangelo, Luigi D., Orange, Jordan, Pannicke, Ulrich, Pearson, Chris, Picco, Paolo, Quinn, Patrick J., Schulz, Ansgar, Seeborg, Filiz, Stray-Pedersen, Asbjørg, Tawamie, Hasan, van Leeuwen, Ester M.M., Aiuti, Alessandro, Yeung, Rae, Schwarz, Klaus, and Kuijpers, Taco W.

Published
2019
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10. Characterization of the clinical and immunologic phenotype and management of 157 individuals with 56 distinct heterozygous NFKB1 mutations

Author

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

Published
2020
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11. A combined immunodeficiency with severe infections, inflammation, and allergy caused by ARPC1B deficiency

Author

Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Volpi, Stefano, Cicalese, Maria Pia, Tuijnenburg, Paul, Tool, Anton T J, Cuadrado, Eloy, Abu-Halaweh, Marwan, Ahanchian, Hamid, Alzyoud, Raed, Akdemir, Zeynep Coban, Barzaghi, Federica, Blank, Alexander, Boisson, Bertrand, Bottino, Cristina, Brigida, Immacolata, Caorsi, Roberta, Casanova, Jean-Laurent, Chiesa, Sabrina, Chinn, Ivan Kingyue, Dückers, Gregor, Enders, Anselm, Erichsen, Hans Christian, Forbes, Lisa R, Gambin, Tomasz, Gattorno, Marco, Karimiani, Ehsan Ghayoor, Giliani, Silvia, Gold, Michael S, Jacobsen, Eva-Maria, Jansen, Machiel H, King, Jovanka R, Laxer, Ronald M, Lupski, James R, Mace, Emily, Marcenaro, Stefania, Maroofian, Reza, Meijer, Alexander B, Niehues, Tim, Notarangelo, Luigi D, Orange, Jordan, Pannicke, Ulrich, Pearson, Chris, Picco, Paolo, Quinn, Patrick J, Schulz, Ansgar, Seeborg, Filiz, Stray-Pedersen, Asbjørg, Tawamie, Hasan, van Leeuwen, Ester M M, Aiuti, Alessandro, Yeung, Rae, Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Volpi, Stefano, Cicalese, Maria Pia, Tuijnenburg, Paul, Tool, Anton T J, Cuadrado, Eloy, Abu-Halaweh, Marwan, Ahanchian, Hamid, Alzyoud, Raed, Akdemir, Zeynep Coban, Barzaghi, Federica, Blank, Alexander, Boisson, Bertrand, Bottino, Cristina, Brigida, Immacolata, Caorsi, Roberta, Casanova, Jean-Laurent, Chiesa, Sabrina, Chinn, Ivan Kingyue, Dückers, Gregor, Enders, Anselm, Erichsen, Hans Christian, Forbes, Lisa R, Gambin, Tomasz, Gattorno, Marco, Karimiani, Ehsan Ghayoor, Giliani, Silvia, Gold, Michael S, Jacobsen, Eva-Maria, Jansen, Machiel H, King, Jovanka R, Laxer, Ronald M, Lupski, James R, Mace, Emily, Marcenaro, Stefania, Maroofian, Reza, Meijer, Alexander B, Niehues, Tim, Notarangelo, Luigi D, Orange, Jordan, Pannicke, Ulrich, Pearson, Chris, Picco, Paolo, Quinn, Patrick J, Schulz, Ansgar, Seeborg, Filiz, Stray-Pedersen, Asbjørg, Tawamie, Hasan, van Leeuwen, Ester M M, Aiuti, Alessandro, and Yeung, Rae

Published
2019

12. Whole Genome Sequencing of Primary Immunodeficiency reveals a role for common and rare variants in coding and non-coding sequences

Author

Thaventhiran, James E. D., Allen, Hana Lango, Burren, Oliver S., Farmery, James H. R., Staples, Emily, Zhang, Zinan, Rae, William, Greene, Daniel, Simeoni, Ilenia, Maimaris, Jesmeen, Penkett, Chris, Stephens, Jonathan, Deevi, Sri V.V., Sanchis-Juan, Alba, Gleadall, Nicholas S, Thomas, Moira J., Sargur, Ravishankar B., Gordins, Pavels, Baxendale, Helen E., Brown, Matthew, Tuijnenburg, Paul, Worth, Austen, Hanson, Steven, Linger, Rachel, Buckland, Matthew S., Rayner-Matthews, Paula J., Gilmour, Kimberly C., Samarghitean, Crina, Seneviratne, Suranjith L., Lyons, Paul A., Sansom, David M., Lynch, Andy G., Megy, Karyn, Ellinghaus, Eva, Ellinghaus, David, Jorgensen, Silje F., Karlsen, Tom H, Stirrups, Kathleen E., Cutler, Antony J., Kumararatne, Dinakantha S., Savic, Sinisa, Burns, Siobhan O., Kuijpers, Taco W., Turro, Ernest, Ouwehand, Willem H., Thrasher, Adrian J., and Smith, Kenneth G. C.

Abstract

Primary immunodeficiency (PID) is characterised by recurrent and often life-threatening infections, autoimmunity and cancer, and it presents major diagnostic and therapeutic challenges. Although the most severe forms present in early childhood, the majority of patients present in adulthood, typically with no apparent family history and a variable clinical phenotype of widespread immune dysregulation: about 25% of patients have autoimmune disease, allergy is prevalent, and up to 10% develop lymphoid malignancies. Consequently, in sporadic PID genetic diagnosis is difficult and the role of genetics is not well defined. We addressed these challenges by performing whole genome sequencing (WGS) of a large PID cohort of 1,318 subjects. Analysis of coding regions of 886 index cases found disease-causing mutations in known monogenic PID genes in 8.2%, while a Bayesian approach (BeviMed 1 ) identified multiple potential new disease-associated genes. Exploration of the non-coding space revealed deletions in regulatory regions which contribute to disease causation. Finally, a genome-wide association study (GWAS) identified novel PID-associated loci and uncovered evidence for co-localisation of, and interplay between, novel high penetrance monogenic variants and common variants (at the PTPN2 and SOCS1 loci). This begins to explain the contribution of common variants to variable penetrance and phenotypic complexity in PID. Thus, a cohort-based WGS approach to PID diagnosis can increase diagnostic yield while deepening our understanding of the key pathways determining variation in human immune responsiveness.

Published
2018
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13. Loss of function NFKB1 variants are the most common monogenic cause of CVID in Europeans

Author

Tuijnenburg, Paul, Lango Allen, Hana, Burns, Siobhan O, Greene, Daniel, Jansen, Machiel H, Staples, Emily, Stephens, Jonathan, Carss, Keren J, Biasci, Daniele, Baxendale, Helen, Thomas, Moira, Chandra, Anita, Kiani-Alikhan, Sorena, Longhurst, Hilary J, Seneviratne, Suranjith L, Oksenhendler, Eric, Simeoni, Ilenia, De Bree, Godelieve J, Tool, Anton TJ, Van Leeuwen, Ester MM, Ebberink, Eduard HTM, Meijer, Alexander B, Tuna, Salih, Whitehorn, Deborah, Brown, Matthew, Turro, Ernest, Thrasher, Adrian J, Smith, Kenneth GC, Thaventhiran, James E, Kuijpers, Taco W, NIHR-BioResource – Rare Diseases Consortium, Lango Allen, Hana [0000-0002-7803-8688], Biasci, Daniele [0000-0003-3148-8152], Thaventhiran, James [0000-0001-8616-074X], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, 03 medical and health sciences, B cells, 030104 developmental biology, 0302 clinical medicine, Common Variable Immunodeficiency, NF-κB1, 030215 immunology
Abstract

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

Published
2018

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

Author

Tuijnenburg, Paul, Lango Allen, Hana, Burns, Siobhan O, Greene, Daniel, Jansen, Machiel H, Staples, Emily, Stephens, Jonathan, Carss, Keren J, Biasci, Daniele, Baxendale, Helen, Thomas, Moira, Chandra, Anita, Kiani-Alikhan, Sorena, Longhurst, Hilary J, Seneviratne, Suranjith L, Oksenhendler, Eric, Simeoni, Ilenia, de Bree, Godelieve J, Tool, Anton T J, van Leeuwen, Ester M M, Ebberink, Eduard H T M, Meijer, Alexander B, Tuna, Salih, Whitehorn, Deborah, Brown, Matthew, Turro, Ernest, Thrasher, Adrian J, Smith, Kenneth G C, Thaventhiran, James E, Kuijpers, Taco W, Tuijnenburg, Paul, Lango Allen, Hana, Burns, Siobhan O, Greene, Daniel, Jansen, Machiel H, Staples, Emily, Stephens, Jonathan, Carss, Keren J, Biasci, Daniele, Baxendale, Helen, Thomas, Moira, Chandra, Anita, Kiani-Alikhan, Sorena, Longhurst, Hilary J, Seneviratne, Suranjith L, Oksenhendler, Eric, Simeoni, Ilenia, de Bree, Godelieve J, Tool, Anton T J, van Leeuwen, Ester M M, Ebberink, Eduard H T M, Meijer, Alexander B, Tuna, Salih, Whitehorn, Deborah, Brown, Matthew, Turro, Ernest, Thrasher, Adrian J, Smith, Kenneth G C, Thaventhiran, James E, and Kuijpers, Taco W

Published
2018

16. High‐throughput compound screen reveals mTOR inhibitors as potential therapeutics to reduce (auto)antibody production by human plasma cells.

Author

Tuijnenburg, Paul, aan de Kerk, Daan J., Jansen, Machiel H., Morris, Ben, Lieftink, Cor, Beijersbergen, Roderick L., Leeuwen, Ester M.M., and Kuijpers, Taco W.

Subjects
ANTIBODY formation, PLASMA cells, MTOR inhibitors, PLASMA production, INTERLEUKIN-21, PROTEIN kinase inhibitors, PHOSPHOINOSITIDES
Abstract

Antibody production by the B cell compartment is a crucial part of the adaptive immune response. Dysregulated antibody production in the form of autoantibodies can cause autoimmune disease. To date, B‐cell depletion with anti‐CD20 antibodies is commonly applied in autoimmunity, but pre‐existing plasma cells are not eliminated in this way. Alternative ways of more selective inhibition of antibody production would add to the treatment of these autoimmune diseases. To explore novel therapeutic targets in signaling pathways essential for plasmablast formation and/or immunoglobulin production, we performed a compound screen of almost 200 protein kinase inhibitors in a robust B‐cell differentiation culture system. This study yielded 35 small cell‐permeable compounds with a reproducible inhibitory effect on B‐cell activation and plasmablast formation, among which was the clinically applied mammalian target of rapamycin (mTOR) inhibitor rapamycin. Two additional compounds targeting the phosphoinositide 3‐kinase‐AKT‐mTOR pathway (BKM120 and WYE‐354) did not affect proliferation and plasmablast formation, but specifically reduced the immunoglobulin production. With this compound screen we successfully applied a method to investigate therapeutic targets for B‐cell differentiation and identified compounds in the phosphoinositide 3‐kinase‐AKT‐mTOR pathway that could specifically inhibit immunoglobulin production only. These drugs may well be explored to be of value in current B‐cell‐depleting treatment regimens in autoimmune disorders. [ABSTRACT FROM AUTHOR]

Published
2020
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17. Loss-of-function nuclear factor κB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans

Author

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

Published
2018
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19. Publisher Correction: Whole-genome sequencing of a sporadic primary immunodeficiency cohort

Author

Thaventhiran, James E. D., Lango Allen, Hana, Burren, Oliver S., Rae, William, Greene, Daniel, Staples, Emily, Zhang, Zinan, Farmery, James H. R., Simeoni, Ilenia, Rivers, Elizabeth, Maimaris, Jesmeen, Penkett, Christopher J., Stephens, Jonathan, Deevi, Sri V. V., Sanchis-Juan, Alba, Gleadall, Nicholas S., Thomas, Moira J., Sargur, Ravishankar B., Gordins, Pavels, Baxendale, Helen E., Brown, Matthew, Tuijnenburg, Paul, Worth, Austen, Hanson, Steven, Linger, Rachel J., Buckland, Matthew S., Rayner-Matthews, Paula J., Gilmour, Kimberly C., Samarghitean, Crina, Seneviratne, Suranjith L., Sansom, David M., Lynch, Andy G., Megy, Karyn, Ellinghaus, Eva, Ellinghaus, David, Jorgensen, Silje F., Karlsen, Tom H., Stirrups, Kathleen E., Cutler, Antony J., Kumararatne, Dinakantha S., Chandra, Anita, Edgar, J. David M., Herwadkar, Archana, Cooper, Nichola, Grigoriadou, Sofia, Huissoon, Aarnoud P., Goddard, Sarah, Jolles, Stephen, Schuetz, Catharina, Boschann, Felix, Lyons, Paul A., Hurles, Matthew E., Savic, Sinisa, Burns, Siobhan O., Kuijpers, Taco W., Turro, Ernest, Ouwehand, Willem H., Thrasher, Adrian J., and Smith, Kenneth G. C.

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020
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20. Characterization of the Clinical and Immunologic Phenotype and Management of 157 Individuals with 56 Distinct Heterozygous NFKB1 Mutations

Author

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

Subjects
0301 basic medicine, Male, NF-KAPPA-B, Medizin, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Fluorescent Antibody Technique, Autoimmunity, Disease, NUCLEAR-FACTOR, Kaplan-Meier Estimate, medicine.disease_cause, Hypogammaglobulinemia, 0302 clinical medicine, NFKB1 variants and mutations, autosomal dominant inheritance, common variable immunodeficiency, reduced penetrance, variable expressivity, HDE PED, Immunology and Allergy, variants and mutations, NF-κB1-related phenotype, Immunodeficiency, IMMUNODEFICIENCY, NF-?B1-related phenotype, 1184 Genetics, developmental biology, physiology, Disease Management, Middle Aged, NF-kappa B1-related phenotype, Prognosis, Penetrance, Immunohistochemistry, Magnetic Resonance Imaging, 3. Good health, Phenotype, NFKB1 variant, Female, Haploinsufficiency, NFKB1 mutation, Adult, Heterozygote, Immunology, HAPLOINSUFFICIENCY, Article, 03 medical and health sciences, autosomal dominant, medicine, Humans, Genetic Predisposition to Disease, Genetic Association Studies, Aged, business.industry, Common variable immunodeficiency, NF-kappa B p50 Subunit, NF-KAPPA-B1, Immune dysregulation, medicine.disease, 030104 developmental biology, Biological Variation, Population, CELLS, Mutation, Primary immunodeficiency, 3111 Biomedicine, business, Tomography, X-Ray Computed, Biomarkers, 030215 immunology
Abstract

Contains fulltext : 229571.pdf (Publisher’s version ) (Closed access) BACKGROUND: An increasing number of NFKB1 variants are being identified in patients with heterogeneous immunologic phenotypes. OBJECTIVE: To characterize the clinical and cellular phenotype as well as the management of patients with heterozygous NFKB1 mutations. METHODS: In a worldwide collaborative effort, we evaluated 231 individuals harboring 105 distinct heterozygous NFKB1 variants. To provide evidence for pathogenicity, each variant was assessed in silico; in addition, 32 variants were assessed by functional in vitro testing of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) signaling. RESULTS: We classified 56 of the 105 distinct NFKB1 variants in 157 individuals from 68 unrelated families as pathogenic. Incomplete clinical penetrance (70%) and age-dependent severity of NFKB1-related phenotypes were observed. The phenotype included hypogammaglobulinemia (88.9%), reduced switched memory B cells (60.3%), and respiratory (83%) and gastrointestinal (28.6%) infections, thus characterizing the disorder as primary immunodeficiency. However, the high frequency of autoimmunity (57.4%), lymphoproliferation (52.4%), noninfectious enteropathy (23.1%), opportunistic infections (15.7%), autoinflammation (29.6%), and malignancy (16.8%) identified NF-κB1-related disease as an inborn error of immunity with immune dysregulation, rather than a mere primary immunodeficiency. Current treatment includes immunoglobulin replacement and immunosuppressive agents. CONCLUSIONS: We present a comprehensive clinical overview of the NF-κB1-related phenotype, which includes immunodeficiency, autoimmunity, autoinflammation, and cancer. Because of its multisystem involvement, clinicians from each and every medical discipline need to be made aware of this autosomal-dominant disease. Hematopoietic stem cell transplantation and NF-κB1 pathway-targeted therapeutic strategies should be considered in the future.

Published
2020
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21. Whole-genome sequencing of a sporadic primary immunodeficiency cohort.

Author

Thaventhiran JED, Lango Allen H, Burren OS, Rae W, Greene D, Staples E, Zhang Z, Farmery JHR, Simeoni I, Rivers E, Maimaris J, Penkett CJ, Stephens J, Deevi SVV, Sanchis-Juan A, Gleadall NS, Thomas MJ, Sargur RB, Gordins P, Baxendale HE, Brown M, Tuijnenburg P, Worth A, Hanson S, Linger RJ, Buckland MS, Rayner-Matthews PJ, Gilmour KC, Samarghitean C, Seneviratne SL, Sansom DM, Lynch AG, Megy K, Ellinghaus E, Ellinghaus D, Jorgensen SF, Karlsen TH, Stirrups KE, Cutler AJ, Kumararatne DS, Chandra A, Edgar JDM, Herwadkar A, Cooper N, Grigoriadou S, Huissoon AP, Goddard S, Jolles S, Schuetz C, Boschann F, Lyons PA, Hurles ME, Savic S, Burns SO, Kuijpers TW, Turro E, Ouwehand WH, Thrasher AJ, and Smith KGC

Subjects
Actin-Related Protein 2-3 Complex genetics, Bayes Theorem, Cohort Studies, Female, Genome-Wide Association Study, Humans, Male, Primary Immunodeficiency Diseases diagnosis, Primary Immunodeficiency Diseases immunology, Protein Tyrosine Phosphatase, Non-Receptor Type 2 genetics, RNA-Binding Proteins genetics, Regulatory Sequences, Nucleic Acid genetics, Suppressor of Cytokine Signaling 1 Protein genetics, Transcription Factors genetics, Primary Immunodeficiency Diseases genetics, Whole Genome Sequencing
Abstract

Primary immunodeficiency (PID) is characterized by recurrent and often life-threatening infections, autoimmunity and cancer, and it poses major diagnostic and therapeutic challenges. Although the most severe forms of PID are identified in early childhood, most patients present in adulthood, typically with no apparent family history and a variable clinical phenotype of widespread immune dysregulation: about 25% of patients have autoimmune disease, allergy is prevalent and up to 10% develop lymphoid malignancies 1-3 . Consequently, in sporadic (or non-familial) PID genetic diagnosis is difficult and the role of genetics is not well defined. Here we address these challenges by performing whole-genome sequencing in a large PID cohort of 1,318 participants. An analysis of the coding regions of the genome in 886 index cases of PID found that disease-causing mutations in known genes that are implicated in monogenic PID occurred in 10.3% of these patients, and a Bayesian approach (BeviMed 4 ) identified multiple new candidate PID-associated genes, including IVNS1ABP. We also examined the noncoding genome, and found deletions in regulatory regions that contribute to disease causation. In addition, we used a genome-wide association study to identify loci that are associated with PID, and found evidence for the colocalization of-and interplay between-novel high-penetrance monogenic variants and common variants (at the PTPN2 and SOCS1 loci). This begins to explain the contribution of common variants to the variable penetrance and phenotypic complexity that are observed in PID. Thus, using a cohort-based whole-genome-sequencing approach in the diagnosis of PID can increase diagnostic yield and further our understanding of the key pathways that influence immune responsiveness in humans.

Published
2020
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