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Your search keyword '"Keavney, Bernard [0000-0001-9573-0812]"' showing total 2 results
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2 results on '"Keavney, Bernard [0000-0001-9573-0812]"'

1. CMV-independent increase in CD27−CD28+ CD8+ EMRA T cells is inversely related to mortality in octogenarians

Author

Rachael Redgrave, Gavin D. Richardson, Carmen Martin-Ruiz, Bernard Keavney, Evgeniya V. Shmeleva, Thomas von Zglinicki, Ioakim Spyridopoulos, Jedrzej Hoffmann, Lilia Draganova, Joanna Collerton, Helen M. Arthur, Shmeleva, Evgeniya [0000-0002-7654-2960], Richardson, Gavin [0000-0002-2310-9987], Draganova, Lilia [0000-0003-1371-104X], Keavney, Bernard [0000-0001-9573-0812], Spyridopoulos, Ioakim [0000-0002-2750-2444], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Senescence, Aging, T cell, 030204 cardiovascular system & hematology, Brief Communication, 03 medical and health sciences, 0302 clinical medicine, 692/53, Medicine, ddc:610, business.industry, brief-communication, Hazard ratio, RC952-954.6, CD28, Immunosenescence, medicine.disease, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, 631/80/509, Geriatrics, Heart failure, Immunology, Geriatrics and Gerontology, business, Serostatus, Biomarkers, CD8
Abstract

Cytomegalovirus (CMV) seropositivity in adults has been linked to increased cardiovascular disease burden. Phenotypically, CMV infection leads to an inflated CD8 T-lymphocyte compartment. We employed a 8-colour flow cytometric protocol to analyse circulating T cells in 597 octogenarians from the same birth cohort together with NT-proBNP measurements and followed all participants over 7 years. We found that, independent of CMV serostatus, a high number of CD27−CD28+ CD8 EMRA T-lymphocytes (TEMRA) protected from all-cause death after adjusting for known risk factors, such as heart failure, frailty or cancer (Hazard ratio 0.66 for highest vs lowest tertile; confidence interval 0.51–0.86). In addition, CD27−CD28+ CD8 EMRA T-lymphocytes protected from both, non-cardiovascular (hazard ratio 0.59) and cardiovascular death (hazard ratio 0.65). In aged mice treated with the senolytic navitoclax, in which we have previously shown a rejuvenated cardiac phenotype, CD8 effector memory cells are decreased, further indicating that alterations in T cell subpopulations are associated with cardiovascular ageing. Future studies are required to show whether targeting immunosenescence will lead to enhanced life- or healthspan.

Published
2020

2. Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing

Author

Sifrim, Alejandro, Hitz, Marc-Phillip, Wilsdon, Anna, Breckpot, Jeroen, Turki, Saeed H Al, Thienpont, Bernard, McRae, Jeremy, Fitzgerald, Tomas W, Singh, Tarjinder, Swaminathan, Ganesh Jawahar, Prigmore, Elena, Rajan, Diana, Abdul-Khaliq, Hashim, Banka, Siddharth, Bauer, Ulrike MM, Bentham, Jamie, Berger, Felix, Bhattacharya, Shoumo, Bu'Lock, Frances, Canham, Natalie, Colgiu, Irina-Gabriela, Cosgrove, Catherine, Cox, Helen, Daehnert, Ingo, Daly, Allan, Danesh, John, Fryer, Alan, Gewillig, Marc, Hobson, Emma, Hoff, Kirstin, Homfray, Tessa, INTERVAL Study, Kahlert, Anne-Karin, Ketley, Ami, Kramer, Hans-Heiner, Lachlan, Katherine, Lampe, Anne Katrin, Louw, Jacoba J, Manickara, Ashok Kumar, Manase, Dorin, McCarthy, Karen P, Metcalfe, Kay, Moore, Carmel, Newbury-Ecob, Ruth, Omer, Seham Osman, Ouwehand, Willem H, Park, Soo-Mi, Parker, Michael J, Pickardt, Thomas, Pollard, Martin O, Robert, Leema, Roberts, David J, Sambrook, Jennifer, Setchfield, Kerry, Stiller, Brigitte, Thornborough, Chris, Toka, Okan, Watkins, Hugh, Williams, Denise, Wright, Michael, Mital, Seema, Daubeney, Piers EF, Keavney, Bernard, Goodship, Judith, UK10K Consortium, Abu-Sulaiman, Riyadh Mahdi, Klaassen, Sabine, Wright, Caroline F, Firth, Helen V, Barrett, Jeffrey C, Devriendt, Koenraad, FitzPatrick, David R, Brook, J David, Deciphering Developmental Disorders Study, Hurles, Matthew E, Sifrim, Alejandro [0000-0001-8247-4020], Thienpont, Bernard [0000-0002-8772-6845], Banka, Siddharth [0000-0002-8527-2210], Pollard, Martin O [0000-0001-8738-0920], Mital, Seema [0000-0002-7643-4484], Keavney, Bernard [0000-0001-9573-0812], Barrett, Jeffrey C [0000-0002-1152-370X], and Apollo - University of Cambridge Repository

Subjects
Heart Defects, Congenital, Male, Protein Conformation, Syndrome, Autoantigens, CDC2 Protein Kinase, Mutation, Humans, Exome, Female, cardiovascular diseases, Protein Kinase C, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Sequence Deletion
Abstract

Congenital heart defects (CHDs) have a neonatal incidence of 0.8-1% (refs. 1,2). Despite abundant examples of monogenic CHD in humans and mice, CHD has a low absolute sibling recurrence risk (∼2.7%), suggesting a considerable role for de novo mutations (DNMs) and/or incomplete penetrance. De novo protein-truncating variants (PTVs) have been shown to be enriched among the 10% of 'syndromic' patients with extra-cardiac manifestations. We exome sequenced 1,891 probands, including both syndromic CHD (S-CHD, n = 610) and nonsyndromic CHD (NS-CHD, n = 1,281). In S-CHD, we confirmed a significant enrichment of de novo PTVs but not inherited PTVs in known CHD-associated genes, consistent with recent findings. Conversely, in NS-CHD we observed significant enrichment of PTVs inherited from unaffected parents in CHD-associated genes. We identified three genome-wide significant S-CHD disorders caused by DNMs in CHD4, CDK13 and PRKD1. Our study finds evidence for distinct genetic architectures underlying the low sibling recurrence risk in S-CHD and NS-CHD.

Published
2016

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