Blog: ‘Let’s not forget children in research on immune system disruption and ME/CFS'

There are signs that certain processes in specific immune cells known as monocytes are disrupted in people with ME/CFS. These are important cells of the immune system involved in communication with nerve cells, among other things. It also seems that the mitochondria – the ‘powerhouses’ of the cell – are damaged in the monocytes. The disruptions in the monocytes can also have implications for nerve cells, preventing them from transmitting signals properly. Researcher Niels Eijkelkamp of UMC Utrecht plans to investigate what exactly is going wrong in the monocytes, and what impact this has on nerve cells. He also plans to study whether antibodies that target the patient’s own body – autoantibodies – might be causing the disruption in the monocytes and, ultimately, the ME/CFS symptoms. 

On part of his research Eijkelkamp is collaborating with Jeroen den Dunnen, an immunologist at Amsterdam UMC (see also the blog on Jeroen den Dunnen). While Den Dunnen is investigating which autoantibodies are the real culprits in ME/CFS, Eijkelkamp is interested in what exactly happens to the metabolism of monocytes. He is also looking at how autoantibodies ‘attack’ the monocytes. 
‘As soon as we have a clearer picture of what mechanisms have been affected, we hope to pinpoint a cause of severe symptoms of ME/CFS’, says Niels Eijkelkamp. ‘This knowledge could help us develop a treatment for ME/CFS in the future.’ 

To find out more about the disruptions in the monocytes and the impact on nerve cells in ME/CFS, blood needs to be collected from ME/CFS patients. The material from adult patients will come from the Dutch ME/CFS Cohort and Biobank consortium (NMCB). ‘I think it’s important that we don’t forget children in our research into ME/CFS. We don’t know exactly how many children are affected by ME/CFS in the Netherlands, but it’s estimated to be about 20,000. Often, we think of children as small adults, but that’s not the case. Their immune system and nervous system are still developing, so it’s important to know whether biological changes – in the mitochondria for example – also happen in children. That’s why we’re including children aged 8 to 18 in our study.'

‘After collecting the blood, we’ll categorise patients on the basis of their bloodwork. This makes research among highly different groups of patients a little easier. We’ll look at the proteins in the blood and at substances that play a role in the immune system. We’ll also look at markers, substances that indicate a particular disease. Specifically, we’ll be looking at substances from the nervous system or immune system, like markers that indicate nerve damage or inflammation. We will make the subgroups with Jeroen den Dunnen. We hope to have 20 to 30 patients in each group. Den Dunnen will identify what autoantibodies the different groups have. Then, my colleagues and I will investigate in the lab, what exactly is going wrong with the metabolism of the monocytes in each subgroup, and what effects this has.’ 

‘So, we’ll be looking specifically at monocytes, using special techniques to look deeper into the cells in the laboratory to find out exactly what’s going wrong. We’ll follow metabolites – tiny metabolic products – in the cell from beginning to end. We’ll also be looking at energy management in the mitochondria, because something is probably going wrong there, too.'

Eijkelkamp also plans to investigate what causes the disruption in the monocytes. Antibodies that target the body’s own immune cells might play a role. He will study how these autoantibodies damage the monocytes. ‘We’ll investigate this in the laboratory by adding the autoantibodies of ME/CFS patients to petri dishes containing immune cells from healthy people, to see whether autoantibodies from people with ME/CFS cause the same changes in the monocytes of healthy people.'

‘We will also investigate whether the changes in the monocytes have implications for nerve cells (see the box down below for more information), by cultivating nerve cells in petri dishes. We’ll then add monocytes that have been disrupted by autoantibodies, and see whether the nerve cells continue to work properly. We’ll also monitor whether the nerve cells acquire new mitochondria from the monocytes.’

‘Finally, we’ll investigate whether the disruptions found in monocytes and nerve cells cause ME/CFS symptoms. We will need to use animal models for this. The autoantibodies will be introduced into mice, then we’ll see whether their monocytes have been affected, and carry out tests to establish whether the mice develop ME/CFS symptoms.'

‘The results of the study should not only help us to gain a better understanding of the disease and the cause of ME/CFS symptoms, but also to develop diagnostic tests for adults and, more especially, children. As soon as we know more about what goes wrong inside the cell, we will probably be able to start thinking about therapies using supplements, like treatment with specific metabolites (metabolic products).'

For more information on the research project and ZonMw’s ME/CFS research programme, visit the pages below.

• Go to the project page
• Go to the consortium website
• Go to the ME/CFS Programme page
• Go to the page on the theme of fatigue

Text: Ilse Bos
Photography: Robert Tjalondo