‘These new results are remarkable, showing a biological signal of ME – a clear sign of abnormal biology in the blood that has only been revealed now that patients have been looked at as a very large group, and that is not due to inactivity.'
By Simon McGrath
In a huge study, researchers at Edinburgh University analysing blood biomarker data have found many differences between people with ME and healthy controls. The team also showed that these differences do not result from inactivity, which blows another hole in the deconditioning theory of ME/CFS.
- The paper is a preprint, which means it hasn’t yet been reviewed by other researchers or published. The authors plan to submit their work for review and publication in a journal.
A big data study
The study by mathematicians and scientists, including DecodeME’s Professor Chris Ponting, used data from UK Biobank (UKB) which enrolled around half a million people when they were aged 40 to 65.
- The UKB is different from the UK ME/CFS Biobank, which is much smaller but has more carefully diagnosed patients.
The study compared up to 1,450 people who reported they had a diagnosis of either chronic fatigue syndrome or ME with just over 130,000 healthy controls. No biomedical study to date has had as many patients and controls. The team looked at 300 blood molecular and cell biomarkers. They also looked at nearly 3,000 proteins in the blood, though in a much smaller group of people with ME.
This is big data, so it was important to have mathematicians taking the lead. They used sophisticated data models that took account of blood biomarker differences between individuals due to age, sex and – critically – activity levels (UKB has three measures of activity, including the average daily time spent walking).
The models showed that hundreds of these blood-based biomarkers were different between people with ME and healthy controls, even after allowing for the small impact of inactivity. 115 of these were significantly different for both men and women. This suggests that women and men share a common basis for the illness.
The cellular and molecular differences found in the blood point to chronic inflammation, insulin resistance and liver disease. The research team said this combination of blood differences is not seen in any other disease they know.
They also said that the differences in blood biomarkers for a chronic illness such as ME are likely to be the consequence of the disease rather than its cause.
No diagnostic biomarker
Despite hundreds of positive findings in the study, no single molecular or cell difference could reliably split those with ME from controls. This isn't surprising as many studies have looked at single biomarkers and found nothing convincing.
So how did this study find so many biomarker differences? Big data: the 1,400+ patients and 130,000+ controls gave this research statistical power to find differences that wouldn't show up in smaller studies.
These differences are modest and/or only affect a subset of people with ME. For example, C-reactive protein (CRP) was significantly higher in patients than controls. Yet only 4.5% of those with ME had CRP levels that would be considered high in normal medical tests, compared with 2.2% than for healthy controls.
Instead, it is the large number of modest differences between people with ME and controls that reveal that something is going on.
Limitations
Like every study, this one has limits. The blood differences might be due to something that hasn't been measured, such as people with ME being on medications or supplements, or eating a different diet.
Further, severely ill (housebound or bedbound) people are unlikely to participate in the biobank, so those with ME/CFS in this study will be more mildly affected than in most studies and might not be typical patients.
These new results are remarkable, showing a biological signal of ME – a clear sign of abnormal biology in the blood that has only been revealed now that patients have been looked at as a very large group, and that is not due to inactivity.