The immune system is crucial in protecting us from disease. Researchers from the Stroke-IMPaCT network have helped conduct a study to see what happens to our immune system following a stroke.

Introduction

When blood stops flowing to a part of the brain, it can cause an ischemic stroke. Ischemic strokes damage the brain and can also change the way a person’s immune system works. Any changes to the way a person’s immune system works can mean a person:

• is less able to fight off infections;
• can take longer to recover from the stroke;
• may never fully recover after the stroke;
• finds that their health continues to get worse after they have had the stroke and that they develop other conditions like dementia.

There is still a lot that scientists don’t know about how a stroke changes the way that the immune system works. To develop treatments to help people after they have had a stroke, it is important to understand exactly how strokes change the way in which the immune system functions.

One way that scientists can do this is by examining the type and behaviour of the immune cells from the blood of people who have had a stroke. This sort of research can be very difficult to do.

One reason for this is that changes to the immune system occur very quickly after a stroke. This means that researchers need to be able to look at the blood of people very soon after they have had a stroke. This is very difficult, because there are many practical and ethical barriers to taking blood samples from people soon after they have had a stroke.

For example, after a stroke people can be very unwell and so the priority has to be doing everything possible to help them survive and recover rather than taking their blood for research.

A second reason is that after a stroke, many people acquire infections. This makes it difficult for researchers to know whether any changes in immune function are because of the stroke or because of an infection.

What did this study investigate?

In this study, the scientists looked at the blood from people in the first three hours after they had had an ischemic stroke. They wanted to know:

• what sorts of immune cells were present in the blood of people up to 3 hours after a stroke;
• if there was a difference in the types of immune cells that were present in the blood of stroke patients compared to people who hadn’t had a stroke.

What did the scientists find?

The researchers saw that the immune cells in the people who had had a stroke were different from those who hadn’t had a stroke in a number of ways. In general, the scientists noticed the following in the blood of people who had had strokes.

• There were changes to a particular sort of immune cell called monocytes. The sort of changes suggested that this particular sort of monocyte would be worse at entering the body’s tissues and not as good at letting the body know about infections after a stroke.
• There was a smaller proportion of a particular sort of immune cells called dendritic cells. Dendritic cells tell other cells in the immune system that a pathogen (germ) has entered the body and teach them how to get rid of the pathogen quickly.
• There was a smaller proportion of a type of B cell. These cells can help the body to get rid of pathogens (germs).

The researchers also found that the people who had had more severe strokes tended to have smaller numbers of a particular type of a specific sort of immune cell that helps the body to recognise and fight pathogens (germs) that it has seen previously. 

What does this tell us?

The findings from this investigation:

• provide further evidence that strokes change the immune system as well as damaging the brain, and that these changes happen very quickly;
• suggest particular sorts of immune cells and particular sorts of changes to them that the scientists should look at further;
• show that it is important to consider how the severity of a stroke changes how the immune system responds.

What do the researchers want to do next?

To continue this work, the researchers want to do the following.

• Perform a larger study using more patients from more than one hospital.

This would help the researchers to be more confident in their findings and help ensure that their findings are the case for all populations, nationalities and races.

• Look at the blood of people who have had had a stroke on different days after they have had a stroke.

This would help the researchers know which changes to the immune system are permanent and which ones are temporary.

• Understand exactly what part of having a stroke causes the changes that are seen in the immune system, and which of the changes to the immune system make the biggest difference to how well a person can recover after a stroke.

This would help the researchers to start to think about ways that they can help people to recover after a stroke.

• Look at the changes seen in a particular population of immune cells that are linked to people with Alzheimer’s disease or mild cognitive impairment.

This may help the researchers start to discover why people who have strokes later develop dementia or cognitive impairment.

• Better understand how having a smaller population of a particular sort of dendritic cells affects the way that people who have had a stroke can fight off infections.

Again, this may help the researchers to start thinking about ways that they can help people to recover after a stroke and be less susceptible to infections.

Study details

Authors: S. Krishnan, C. O’Boyle, C.J Smith, S. Hulme, S.M. Allan, J.R. Grainger, C.B. Lawrence.

Published title: A hyperacute immune map of ischaemic stroke patients reveals alterations to circulating innate and adaptive cells.

Published article: https://doi.org/10.1111/cei.13551

Funders:

This study was funded by grants from:

• the Dowager Countess Eleanor Peel Trust and Medical Research Council (MR/K501311/1) to O’Boyle;
• the President’s Doctoral Scholar Award from The University of Manchester to Krishnan;
• a Senior Fellowship funded by The Kennedy Trust for Rheumatology Research;
• a Sir Henry Dale Fellowship funded by The Wellcome Trust and The Royal Society (104195/Z/14/Z);
• a University of Manchester Institutional Strategic Support Fund Stepping Stones fellowship supported by The Wellcome Trust (grant 097820/Z/11/B) to R. Grainger.

We also acknowledge the Stroke IMPaCT Leducq Foundation (grant 19CVD01) award to S.M. Allan and C.J Smith.

The SCIL‐STROKE study was funded by the Stroke Association award (grant TSA 2012/08) to C.J Smith and S.M. Allan.

Related