A potential trigger for cryptogenic strokes in young adults is the long-lived hyper-inflammation associated with chronic peripheral inflammatory diseases including inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). These diseases involve systemic inflammatory responses, similar to that observed during acute infection, and are relatively common in the UK population, cumulatively affecting almost 1 million people.
Our hypothesis is that heightened thromboinflammatory responses during peripheral inflammatory diseases drive increased incidence and/or severity of stroke.
To test this hypothesis we will access and analyse electronic health records held in large, longitudinal patient registries of patients with confirmed diagnosis of IBD (https://ibdregistry.org.uk) or RA (https://bioresource.nihr.ac.uk/centres-programmes/imid-bioresource). We will compare the incidence of imaging-confirmed, ischaemic stroke in each patient population compared to a healthy (i.e. without diagnosis of inflammatory disease) control population. Sub-group analyses, within each registry, will also be performed to assess patient’s disease activity (documented clinical exacerbations/flares and serial inflammation measures) and biologic treatment status prior to stroke diagnosis. This will generate the first estimates of the increased stroke risk associated with inflammatory diseases that are based on longitudinal, real-world data and take into account fluctuations in disease activity and treatments.
Available plasma samples from IBD and RA patients with confirmed ischaemic stroke will be retrieved from the NIHR National Biosample Centre along with all available samples from an equal-sized and matched, stroke-free patient group from each registry and equal-sized, matched healthy control groups from the NIHR blood donors Bioresource. In house ELISAs and commercially available LengendPLEX panels will be used to measure pro-inflammatory cytokines, markers of thromboinflammation and fibrinolysis factors. This cross-sectional analysis aims to identify pre-existing thromboinflammation in patients with inflammatory disease who have gone on to have a stroke, compared to those that have not, and will be the first step in assigning a causal link between these pathologies.
Entry Requirements
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area/subject. Candidates with previous laboratory experience are particularly encouraged to apply.
How To Apply
For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title.
For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/”
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