The latest list of publications from the Cambridge Biomedical Research Centre with a brief summary.
Publication: PLOS Medicine
David Wastlund, Alexandros A. Moraitis, Alison Dacey, Ulla Sovio, Edward C. F. Wilson, Gordon C. S. Smith
16 April 2019
Despite the relative ease with which breech presentation can be identified through ultrasound screening, the assessment of foetal presentation at term is often based on clinical examination only. Due to limitations in this approach, many women present in labour with an undiagnosed breech presentation, with increased risk of foetal morbidity and mortality. This study sought to determine the cost effectiveness of universal ultrasound scanning for breech presentation near term (36 weeks of gestational age [wkGA]) in nulliparous women.View publication
Publication: Frontiers in Immunology
Manu Chhabra, Jawaher Alsughayyir, M. Saeed Qureshi, Mekhola Mallik, Jason M. Ali, Ivonne Gamper, Ellen L. Moseley, Sarah Peacock, Vasilis Kosmoliaptsis, Martin J. Goddard, Michelle A. Linterman, Reza Motallebzadeh and Gavin J. Pettigrew
23 January 2019
Different profiles of alloantibody responses are observed in the clinic, with those that persist, often despite targeted treatment, associated with poorer long-term transplant outcomes. Although such responses would suggest an underlying germinal center (GC) response, the relationship to cellular events within the allospecific B cell population is unclear. Here we examine the contribution of germinal center (GC) humoral alloimmunity to chronic antibody mediated rejection (AMR)…
This work is composed of two parts, of which this is Part II. Please read also Part I: Alsughayyir et al., 2019.View publication
Publication: Frontiers in Immunology
Jawaher Alsughayyir, Manu Chhabra, M. Saeed Qureshi, Mekhola Mallik, Jason M. Ali, Ivonne Gamper, Ellen L. Moseley, Sarah Peacock, Vasilis Kosmoliaptsis, Martin J. Goddard, Michelle A. Linterman, Reza Motallebzadeh, Gavin J. Pettigrew
22 January 2019
Humoral alloimmunity is now recognized as a major determinant of transplant outcome. MHC glycoprotein is considered a typical T-dependent antigen, but the nature of the T cell alloresponse that underpins alloantibody generation remains poorly understood. This paper examines how the relative frequencies of alloantigen-specific B cells and helper CD4 T cells influence the humoral alloimmune response and how this relates to antibody-mediated rejection (AMR).View publication
Publication: BMJ Open
John OO Ayorinde, Dominic M Summers, Laura Pankhurst, Emma Laing, Alison J Deary, Karla Hemming, Edward CF Wilson, Victoria Bardsley, Desley A Neil, Gavin J Pettigrew
17 January 2019
Most potential kidney transplant donors in the UK are aged over 60 years, yet increasing donor age is associated with poorer graft survival and function. Urgent preimplantation kidney biopsy can identify chronic injury, and may aid selection of better ‘quality’ kidneys from this group. However, the impact of biopsy on transplant numbers remains unproven. The PreImplantation Trial of Histopathology In renal Allografts (PITHIA) study will assess whether the introduction of a national, 24 hours, digital histopathology service increases the number, and improves outcomes, of kidneys transplanted in the UK from older deceased donors.View publication
Publication: Journal of Hepatology
Rhiannon Taylor, Elisa Allen, James A. Richards, Mingzheng A. Goh, James Neuberger, David Collett, Gavin J. Pettigrew, Liver Advisory Group to NHS Blood and Transplant
11 January 2019
This study looks at patients who require a liver transplant to save their lives; this liver can be donated by a person who has died either after their heart has stopped (donation after cardiac death – DCD) or after the brain has been injured and can no longer support life (donation after brainstem death – DCB). We know that livers donated after brainstem death function better than those after cardiac death, but there are not enough of these livers for everyone, so we wished to help patients decide whether it was better for them to accept an early offer of a DCD liver than waiting longer to receive a “better” liver from a DBD donor. We found that patients were more likely to survive if they accepted the offer of a liver transplant as soon as possible (DCD or DBD), especially if their liver disease was very severe.View publication
Publication: American Journal of Transplantation
Ines G. Harper, Olivera Gjorgjimajkoska, Jacqueline H. Y. Siu, Jasvir Parmar, Arend Mulder, Frans H. J. Claas, Sarah A. Hosgood, Michael L. Nicholson, Reza Motallebzadeh, Gavin J. Pettigrew
12 December 2018
Tissue resident lymphocytes are present within many organs, and are presumably transferred at transplantation, but their impact on host immunity is unclear. Here, we examine whether transferred donor natural regulatory CD4 T cells (nT‐regs) inhibit host alloimmunity and prolong allograft survival.View publication
Publication: Journal of Autoimmunity
M. Saeed Qureshi, Jawaher Alsughayyir, Manu Chhabra, Jason M. Ali, Martin J. Goddard, Christopher A. Devine, Thomas M. Conlon, Michelle A. Linterman, Reza Motallebzadeh, Gavin J.Pettigrew
7 December 2018
The development of humoral autoimmunity following organ transplantation is increasingly recognised, but of uncertain significance. We examine whether autoimmunity contributes independently to allograft rejection.View publication
Publication: Frontiers in Immunology
Jacqueline H. Y. Siu, Veena Surendrakumar, James A. Richards and Gavin J. Pettigrew
5 November 2018
Transplantation is unusual in that T cells can recognize alloantigen by at least two distinct pathways: as intact MHC alloantigen on the surface of donor cells via the direct pathway; and as self-restricted processed alloantigen via the indirect pathway. Direct pathway responses are viewed as strong but short-lived and hence responsible for acute rejection, whereas indirect pathway responses are typically thought to be much longer lasting and mediate the progression of chronic rejection. However, this is based on surprisingly scant experimental evidence, and the recent demonstration that MHC alloantigen can be re-presented intact on recipient dendritic cells—the semi-direct pathway—suggests that the conventional view may be an oversimplification.View publication
Jason M. Ali, Margaret C. Negus, Thomas M. Conlon, Ines G. Harper, M. Saeed Qureshi, Reza Motallebzadeh, Richard Willis, Kourosh Saeb-Parsy, Eleanor M. Bolton, J. Andrew Bradley, Gavin J. Pettigrew
9 February 2016
MHC alloantigen is recognized by two pathways: “directly,” intact on donor cells, or “indirectly,” as self-restricted allopeptide. The duration of each pathway, and its relative contribution to allograft vasculopathy, remain unclear. Using a murine model of chronic allograft rejection, we report that direct-pathway CD4 T cell alloresponses, as well as indirect-pathway responses against MHC class II alloantigen, are curtailed by rapid elimination of donor hematopoietic antigen-presenting cells. In contrast, persistent presentation of epitope resulted in continual division and less-profound contraction of the class I allopeptide-specific CD4 T cell population, with approximately 10,000-fold more cells persisting than following acute allograft rejection. This expanded population nevertheless displayed sub-optimal anamnestic responses and was unable to provide co-stimulation-independent help for generating alloantibody. Indirect-pathway CD4 T cell responses are heterogeneous. Appreciation that responses against particular alloantigens dominate at late time points will likely inform development of strategies aimed at improving transplant outcomes.View publication
Publication: Frontiers in Behavioural Neuroscience
George Savulich, Emily Thorp, Thomas Piercy, Katie A Peterson, John D Pickard, Barbara J Sahakian.
21 Jan 2019
A new ‘brain training’ game designed by researchers at the University of Cambridge improves users’ concentration, according to new research published today. The scientists behind the venture say this could provide a welcome antidote to the daily distractions that we face in a busy world.
A team from the Behavioural and Clinical Neuroscience Institute at the University of Cambridge, has developed and tested ‘Decoder’, a new game that is aimed at helping users improve their attention and concentration. The game is based on the team’s own research and has been evaluated scientifically.
In a study published in the journal Frontiers in Behavioural Neuroscience Professor Sahakian and colleague Dr George Savulich have demonstrated that playing Decoder on an iPad for eight hours over one month improves attention and concentration. This form of attention activates a frontal-parietal network in the brain. Read the full story hereView publication
Publication: Oxford Academic
Lisa Pennells, Stephen Kaptoge, AngelaWood, Mike Sweeting , Xiaohui Zhao, Ian White, Stephen Burgess, Peter Willeit, Thomas Bolton, Karel G.M. Moons, Yvonne T. van der Schouw, Randi Selmer, Kay-Tee Khaw, Vilmundur Gudnason, Gerd Assmann, Philippe Amouyel, Veikko Salomaa, Mika Kivimaki, Børge G. Nordestgaard, Michael J. Blaha, Lewis H. Kuller, Hermann Brenner, Richard F. Gillum, Christa Meisinger, Ian Ford, MatthewW. Knuiman, Annika Rosengren, Debbie A. Lawlor, Henry Vo¨ lzke, Cyrus Cooper, Alejandro Marı´n Iba~nez, Edoardo Casiglia, Jussi Kauhanen, Jackie A. Cooper, Beatriz Rodriguez, Johan Sundstro¨m, Elizabeth Barrett-Connor, Rachel Dankner, Paul J. Nietert, KarinaW. Davidson, Robert B.Wallace, Dan G. Blazer, Cecilia Bjo¨ rkelund, Chiara Donfrancesco, Harlan M. Krumholz, Aulikki Nissinen, Barry R. Davis, Sean Coady, Peter H.Whincup, Torben Jørgensen, Pierre Ducimetiere, Maurizio Trevisan, Gunnar Engstro¨m, Carlos J. Crespo, TomW. Meade, Marjolein Visser, Daan Kromhout, Stefan Kiechl, Makoto Daimon, Jackie F. Price, Agustin Go´mez de la Ca´mara, JWouter Jukema, Benoıˆt Lamarche, Altan Onat, Leon A. Simons, Maryam Kavousi, Yoav Ben-Shlomo, John Gallacher, Jacqueline M. Dekker, Hisatomi Arima, Nawar Shara, RobertW. Tipping, Ronan Roussel, Eric J Brunner, Wolfgang Koenig, Masaru Sakurai, Jelena Pavlovic, Ron T. Gansevoort, Dorothea Nagel, Uri Goldbourt, Elizabeth L.M. Barr, Luigi Palmieri, Inger Njølstad, Shinichi Sato,W.M. Monique Verschuren, Cherian V. Varghese, Ian Graham, Oyere Onuma, Philip Greenland, MarkWoodward, Majid Ezzati, Bruce M. Psaty, Naveed Sattar, Rod Jackson, Paul M. Ridker, Nancy R. Cook, Ralph B. D’Agostino,View publication
Loes CA Rutten-Jacobs, Susanna C Larsson,, Rainer Malik,, Kristiina Rannikmäe, MEGASTROKE consortium, International Stroke Genetics Consortium, Cathie L Sudlow, Martin Dichgans, Hugh S Markus, professor2, Matthew Traylor
Researchers investigated whether a genetic risk score for stroke is associated with actual (“incident”) stroke in a large population of British adults.
They developed a genetic risk score based on 90 gene variants known to be associated with stroke from 306,473 white men and women in the UK Biobank – a database of biological information from half a million British adults.
Participants were aged between 40 and 73 years and had no history of stroke or heart attack. Adherence to a healthy lifestyle was based on four factors: non-smoker, diet rich in fruit, vegetables and fish, not overweight or obese (body mass index less than 30), and regular physical exercise.
A high genetic risk combined with an unfavourable lifestyle profile was associated with a more than twofold increased risk of stroke compared with a low genetic risk and a favourable lifestyle. Full story hereView publication