B-cells in stroke-associated infection
Research type
Research Study
Full title
Understanding stroke-induced B cell changes and their relationships with stroke-associated infection
IRAS ID
237040
Contact name
Craig Smith
Contact email
Sponsor organisation
Salford Royal NHS Foundation Trust
Duration of Study in the UK
2 years, 3 months, 31 days
Research summary
Summary of Research
Why - The study will examine the affect that stroke has on the body’s immune system. The most frequent complication of stroke that reduces the chances of a good recovery is infection, particularly from bacteria causing pneumonia in the lungs, which normally occurs in the first few days after stroke. At the moment, there are no treatments that are effective at reducing stroke-associated infection.What – A blood sample will be obtained from stroke patients between 24-48h hours of admission to hospital to measurement of levels of b-cells (type of immune cell in the blood) and to observe how stroke changes their function. Further assessments will be performed at 7days from stroke onset to record infection and antibiotic therapy and at 3month to assess functional recovery (modified Rankin Scale).
Who - The study will recruit patients who have suffered a stroke, caused either by a blocked artery (ischaemic) or a bleed (intracerebral haemorrhage) and who have difficulty with swallowing putting them at a higher risk of pneumonia. In addition, a single blood sample will be obtained from people with no history of stroke (controls).
Where/How –Participants will be recruited from Salford Royal NHS Foundation Trust beginning on 1st July, 2018 with follow-up completed by 3oth June, 2020. Recruitment of non-stroke volunteers and analysis of data will be completed no later than 31st October, 2020.
Summary of Research
In this research study we showed that following acute ischaemic stroke, the abundance and function
of marginal zone (MZ)-like B cells, a subset of B cells in the blood, are markedly reduced. Release of
antibodies (immunoglobulin (Ig) M), a key factor important in anti-bacterial responses, and other
inflammatory molecules, from these cells were impaired. Lower MZ-like B cell frequencies were
associated with mortality and dependence at 3 months, but not when severity of stroke was taken
into account. Reduction of MZ-like B cell numbers was not associated with development of infection.
Taken together, these findings demonstrate stroke rapidly alters specific subsets of blood B cells and
highlight altered innate-like B cell function as an important feature of the immunological response to
acute stroke.
Dissemination, outputs and impact:
Findings from this research has been presented at several scientific meetings including Stroke
Immunology, British Society of Immunology and European Stroke Organisation Conference. Work
from this study formed part of a successful PhD thesis. The main research paper that describes the
full results of the study is currently under review in Journal of Clinical Investigation Insights.
Patient and public involvement:
We have disseminated the main findings of the study to our local PPIE group.
Conclusions and future plans:
This project, along with companion studies in experimental stroke has found that certain B cell
subsets are significantly altered after a stroke, with reduction of the numbers and functionality
(including reduced antibody production) of subsets that are important in defence against infections.
Although we did not find a definite link between MZ-like B cells and development of infection, this
remains a possibility which we think requires further study. Plans are currently in place to evaluate
immunoglobulin therapy as a means of helping to prevent stroke-associated infections, initially in
experimental stroke.Summary of Results
In this research study we showed that following acute ischaemic stroke, the abundance and function of marginal zone (MZ)-like B cells, a subset of B cells in the blood, are markedly reduced. Release of antibodies (immunoglobulin (Ig) M), a key factor important in anti-bacterial responses, and other inflammatory molecules, from these cells were impaired. Lower MZ-like B cell frequencies were associated with mortality and dependence at 3 months, but not when severity of stroke was taken into account. Reduction of MZ-like B cell numbers was not associated with development of infection.
Taken together, these findings demonstrate stroke rapidly alters specific subsets of blood B cells and highlight altered innate-like B cell function as an important feature of the immunological response to acute stroke.This project, along with companion studies in experimental stroke has found that certain B cell subsets are significantly altered after a stroke, with reduction of the numbers and functionality (including reduced antibody production) of subsets that are important in defence against infections. Although we did not find a definite link between MZ-like B cells and development of infection, this remains a possibility which we think requires further study. Plans are currently in place to evaluate immunoglobulin therapy as a means of helping to prevent stroke-associated infections, initially in experimental stroke.
REC name
North West - Greater Manchester South Research Ethics Committee
REC reference
18/NW/0415
Date of REC Opinion
2 Jul 2018
REC opinion
Favourable Opinion