Tracking peripheral immune cell infiltration of the brain in ME

Principal Investigator

Prof. Jarred Younger


University of Alabama at Birmingham, Birmingham, Alabama, USA

Start date

June 2018

Background and aim

Many of the characteristic symptoms of ME/CFS suggest that the immune system is activated in the brains of people with the illness, leading to the release of inflammatory chemicals.

This neuroinflammation is known to cause a variety of symptoms, including  fatigue, pain sensitivity, cognitive problems and sleep disturbances, all of which are common in people with ME/CFS. But how might this occur?

The central hypothesis behind a new project, funded by ME Research UK and led by Prof. Jarred Younger at the University of Alabama, is that activated immune cells from elsewhere in the body infiltrate the brain, so driving these symptoms of ME/CFS.

Prof. Younger explains that the brain and body have distinct immune systems which are separated by what is known as the blood-brain barrier. These two immune systems employ different kinds of cells: microglia in the brain, and T cells, B cells and NK cells in the rest of the body.

During neuroinflammation, the blood-brain barrier can become damaged, allowing peripheral immune cells to infiltrate the brain, and this has been observed in other neuroinflammatory disorders such as multiple sclerosis. These infiltrating T cells can then push the native microglia of the brain into an activated and inflammatory state.

To investigate whether this is happening in ME/CFS, Prof. Younger and his team plan to track peripheral immune cells and see whether they do indeed break the blood-brain barrier and infiltrate the brain.

This is quite a challenge, and the team has developed a new technique where they will take a sample of the patients’ own peripheral immune cells, label them with a radioisotope called zirconium-89, and inject them back into the patients. The investigators will then use positron emission scanning to track the cells and detect whether they enter the brain.

The plan is to study 15 women with ME/CFS and 10 age-matched healthy control women, and to scan them at 24 hours and then 96 hours following the injection. This should allow enough time for the cells to cross the blood-brain barrier (if they are going to).

As well as advancing our understanding of the pathogenesis of ME/CFS and the role of the immune system, the results of this study may indicate that neuroinflammation is a worthwhile target for treatment of the illness, and even help in establishing a diagnostic test that can distinguish between patients and healthy control subjects.

Prof. Younger spoke about this study during his talk at the NIH conference in April 2019. His talk begins at around 4 hr 5 min.

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