Identification of actin network proteins, talin-1 and filamin-A, in circulating extracellular vesicles as blood biomarkers...ME/CFS 2019, Eguchi et al

The finding of increased extracellular vesicles in people with ME/CFS looks pretty solid for the population they were sampling in. I can't comment on the methodology and the version of the report I'm looking at doesn't have the figures and tables.

Sample 1 - 33 healthy controls; 39 people with Fukuda ME/CFS.
# of EVs was higher in ME/CFS P=0.001

Sample 2 - another 30 people with Fukuda ME/CFS.
#of EVs was higher in ME/CFS (presumably compared to Sample 1 HCs). P=0.001
They also note that the ME/CFS #EVs of Sample 1 was 'similar' to that of Sample 2.

Sample 3? - 20 healthy controls; 30 people with Fukuda ME/CFS.
Me/CFS # EVs also significantly higher. P=0.001
(The way it is written suggests to me that the 30 ME/CFS were in addition to those of Sample 2)

Supplementary Fig 1B hopefully makes it clear. Edit: in the methods they talk about 99 ME/CFS patients in the study, so it seems likely there were those 3 separate samples.

Edit - it is later noted that the number of EVs was not significantly different between people with depression (8), ME/CFS (99) or idiopathic chronic fatigue (6).

 

They found a correlation between CRP and # of EVs.

They noted that this correlation was true even with data points within the normal range for CRP.

They comment that CRP is a marker known to be increased in ME/CFS, quoting Fukuda 2016
Fukuda, S., Nojima, J., Motoki, Y., Yamaguti, K., Nakatomi, Y., Okawa, N., Fujiwara, K., Watanabe, Y., Kuratsune, H., 2016. A potential biomarker for fatigue: Oxidative stress and anti- oxidative activity. Biological psychology 118, 88-93.

I haven't heard this talked of elsewhere, in fact I thought I had heard the opposite, that CRP is not different. And I keep an eye on that, because my CRP levels have been consistently moderately elevated since becoming ill. I wonder if there is anything different between the Japanese ME/CFS population sampled here and ME/CFS populations elsewhere.

 

In contrast to the #EV study, the determination of what is in the EVs was much more of a pilot study.

They purified EVs from the plasma of 3 healthy controls and 3 PwME. There were 124 proteins identified overall, with a number of proteins only in PwME or only in HCs. 75 of the proteins were significantly different in PwME compared to healthy controls - which is quite remarkable given the small sample size. I don't know if they accounted for multiple comparisons in that, probably not.

They identified specific pathways that the proteins that were significantly different seemed to be relevant to:

Then they analysed the contents of EVs for 4 PwME, 4 with depression and 4 with idiopathic chronic fatigue.
they used a different process for concentrating the EVs I think, I'm not sure what impact this had, but this time a total of 579 proteins were identified.

At this point I was despairing slightly, over the size of the EV characterisation samples and so on. But this point was encouraging:

So they seemed to find the same differences between PwME and (depression and ICF) as they had found between PwME and healthy controls.
These quotes are the guts of it:

Where it says '12 most abundant proteins in the EVs' - I assume they mean, of the 31 proteins identified as significantly different. Table 1 has this data, so it would be worth looking to see exactly how they chose those 12.

 

So, looks like early days to me. I'm not going to spend time googling actinin etc at this point. I think Maureen Hanson's team is working on EVs, it will be interesting to see what they come up with.

Where to start with the suggestion that the fact that GET helps people with ME/CFS indicates there is a muscle damage problem.

Hmm

Before I finish up, I just want to comment on this:

What a weird three symptoms to pick to characterise ME/CFS. Depression? I don't know where they are getting that from.