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

Overview of attention for article published in The Journal of Allergy and Clinical Immunology, October 2018
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2 Facebook pages

Citations

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32 Dimensions

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72 Mendeley
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Title
Loss-of-function nuclear factor κB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans
Published in
The Journal of Allergy and Clinical Immunology, October 2018
DOI 10.1016/j.jaci.2018.01.039
Pubmed ID
Authors

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

Abstract

The genetic etiology of primary immunodeficiency disease (PID) carries prognostic information. We conducted a whole-genome sequencing study assessing a large proportion of the NIHR-BioResource - Rare Disease cohort. 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. 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. 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.

Twitter Demographics

The data shown below were collected from the profiles of 8 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 72 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 72 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 13 18%
Student > Ph. D. Student 13 18%
Other 7 10%
Professor 6 8%
Student > Bachelor 5 7%
Other 14 19%
Unknown 14 19%
Readers by discipline Count As %
Immunology and Microbiology 18 25%
Medicine and Dentistry 16 22%
Biochemistry, Genetics and Molecular Biology 8 11%
Agricultural and Biological Sciences 6 8%
Social Sciences 2 3%
Other 0 0%
Unknown 22 31%

Attention Score in Context

This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 September 2019.
All research outputs
#3,649,252
of 14,526,769 outputs
Outputs from The Journal of Allergy and Clinical Immunology
#3,414
of 8,294 outputs
Outputs of similar age
#85,789
of 275,490 outputs
Outputs of similar age from The Journal of Allergy and Clinical Immunology
#115
of 203 outputs
Altmetric has tracked 14,526,769 research outputs across all sources so far. This one has received more attention than most of these and is in the 74th percentile.
So far Altmetric has tracked 8,294 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.6. This one has gotten more attention than average, scoring higher than 58% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 275,490 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 68% of its contemporaries.
We're also able to compare this research output to 203 others from the same source and published within six weeks on either side of this one. This one is in the 43rd percentile – i.e., 43% of its contemporaries scored the same or lower than it.