Thesis Characterising the Electrophysiological Properties of Cells in Health and Disease [on ME/CFS], 2024, Clarke

[ME/CFS Science Blog]

Don't quite understand why figure 32 (below) shows decreases in % change in zeta-potential in ME/CFS patients while on Figure 21 that Murph posted above, it seems that zeta-potential increased after 1.5 hours in the ME/CFS patients.


Figure 32| Normalised ζ-potential data for PBMCs incubated in hyperosmotic NaCl media for 1.5 hours in severe ME/CFS (blue circles: n = 8), mild/moderate ME/CFS (red squares: n = 9), healthy controls (green triangles: n = 6) and MS (purple inverted triangles: n = 4). |A| The change in ζ-potential (%)

 

[petrichor]

Don't quite understand why figure 32 (below) shows decreases in % change in zeta-potential in ME/CFS patients while on Figure 21 that Murph posted above, it seems that zeta-potential increased after 1.5 hours in the ME/CFS patients.

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Figure 32| Normalised ζ-potential data for PBMCs incubated in hyperosmotic NaCl media for 1.5 hours in severe ME/CFS (blue circles: n = 8), mild/moderate ME/CFS (red squares: n = 9), healthy controls (green triangles: n = 6) and MS (purple inverted triangles: n = 4). |A| The change in ζ-potential (%)

I think it's because the zeta-potentials are negative values, and the "Change in zeta-potential" would have been calculated something like: (NaCl zeta potential value minus zeta potential value with no NaCl) divided by zeta potential value with no NaCl. That would give a negative number minus bigger negative number = positive number, then divided by zeta potential value with no NaCl (which is negative). That would give a negative value as a result

Whereas the magnitude changes are just the absolute values of the percent changes

 

[EndME]

Does anybody have a summary of what is going on? Skimming the thread I was under the impression the Nanoneedle findings by Davis et al didn't "replicate"(it's not quite the same experiment so I'm not sure whether it makes sense to talk of replication) but that they might have found a different angle that is worth further exploring and that has the potential to be able to give explainable clues? What could such clues be related to?

 

[hotblack]

My understanding was the original Davis test was just about impedance in white blood cells while the work here expanded the approach to look at a range of cell properties and found an ability to differentiate using ionic content in the cytoplasm, ion transport through and across the surface of the cell, and the cell surface charge.

So yeah, not replication but something which seems to be related and they could then get to work using standard commercial equipment. There’s more in this write up.

And this is the bit from the new funding announcement that seemed key to me

• explore how ion channels and plasma ions affect these electrical differences, and test whether a treatment called low-dose naltrexone (LDN) can help.

It would be good to get more information with specifics from either those running or funding this new study though.

Not sure if that helps add anything @EndME but it helped me trying to summarise it

 

[Jonathan Edwards]

It would certainly be useful to have more information. The first problem with looking at electrical properties of peripheral blood mononuclear cells is that any differences between ME/CFS and normals might relate to proportions of the wide range of cell types included and also their ageing status. No doing much exercise may change how long blood cells last in the circulation etc.

If there is a general abnormality of ion transport this might show up but so far we have not really had any reason to think there would be in ME/CFS. The Davis work measured impedance along the membrane as I understand it (at nanoscale), which would likely have nothing to do with ion transport across the membrane.

What may be useful here is developing a way to use the electrical testing as a readout for specific immune cell reactions to sera, other cells etc.. To make much of that you probably need to sort the cells into types but that is what Jackie Cliff does all the time so no problem there.

I am not sure that there is any coherent hypothesis or data thread from Davis to here but this may be one of those situations where exploring a method provides a way in to otherwise invisible events.