[IgG] Complexes from infectious ME/CFS, including post-COVID ME/CFS Disrupt Cellular Energetics and Alter Inflammatory Marker Secretion, 2026, Prusty+

jnmaciuch said:
Somewhat. If antibodies induced substantial differences in mitochondrial capacity then you might expect to see that in the Ryback study too (though different cell types were used and that could theoretically make a difference).

But that wasn't a main finding in this paper anyways, and the Ryback study didn't measure mitochondrial fragmentation, which was the main (albeit weak) finding of this paper
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Two things to note:
1. It was the antigen / antibody immune complex which was exposed to the cultured cell lines, not just IgG.
2. The IgG immune complex was selectively taken up by HUVEC cells but not Human Foreskin Fibroblasts.

Notably, they split-off the FC and Fab fragments in order to investigate the effect that would have and found that the complete IgG immune complex was needed in order to bring about alterations in the Mitochondrial architecture.
 
Paul Watton said:
Two things to note:
1. It was the antigen / antibody immune complex which was exposed to the cultured cell lines, not just IgG.
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The trouble is that we have no idea what these 'immune complexes' are. We spent a three decades in the 1960s-1980s trying to make sense of immune complexes in diseases where we are pretty sure they are crucial and it was never possible to make much of the findings. A real life immune complex is a transient state that may last minutes and during that time undergoes a series of changes in composition. More stable immune complexes probably, almost by definition, probably don't do much. We gave up this sort of work in RA by 1990.
 
Paul Watton said:
1. It was the antigen / antibody immune complex which was exposed to the cultured cell lines, not just IgG.
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Yes that's implied when I state that samples were exposed to IgG from blood samples, because the way you sort IgG is through a Protein G pull-down, which would not discriminate between bound and unbound antibody. Either way it's not relevant to the point you're quoting, since if immune complexes purified from the blood were the deciding factor, they'd also be present in the Ryback study samples.

Paul Watton said:
2. The IgG immune complex was selectively taken up by HUVEC cells but not Human Foreskin Fibroblasts.
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Yes, as I already noted, it could be a cell-type specific effect. And per your last point:

Paul Watton said:
Notably, they split-off the FC and Fab fragments in order to investigate the effect that would have and found that the complete IgG immune complex was needed in order to bring about alterations in the Mitochondrial architecture.
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You're right that only the unfragmented IgG induced (small effect size, small n) changes in mitochondrial surface area, despite both Fab and Fc fragments being perfectly capable of entering the HUVECs on their own. That doesn't mean that immune complexes were required, it only means that whole IgG was required--HUVECs express neonatal Fc receptors, which have an important role in internalizing unbound IgG.

The fact that only HUVECs showed this difference is actually support that immune complexes don't matter, since fibroblasts express regular Fc receptors specifically for phagocytosis of immune complexes. And regardless, they failed to show that this small difference in mitochondrial fragmentation has an important functional effect.
 
Well that sucks. Are there doubts about Prusty? Sometimes researchers have their own pet theories and adjust their research to push it.
 
How big of a finding is it that patients IgG enters these endothelial cells yet healthy controls don't?
Even if the differences in o2 consumption were minor to my untrained eye this shows that the disease could be caused by IgG antibodies. Are there any other normal circumstances were IgG would enter endothelial cells, like if the patient was sick in some other way?
 
sb4 said:
How big of a finding is it that patients IgG enters these endothelial cells yet healthy controls don't?
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I think all IgG entered the endothelial cells?

HUVECs were permissive to human IgG, while HFFs did not allow entry of IgG into the cells (Fig. 1C), suggesting cell-specific selective entry of IgG into human cells. IgG entry into HUVEC cells was also confirmed using immunofluorescence staining of human IgG (Fig. 1D). IgG that entered HUVEC cells was efficiently detectable up to 16 h post-exposure (Fig. 1E). However, IgG levels decreased within the cells in a time-dependent manner (Fig. 1E), suggesting potential IgG recycling and degradation within the cell. Fc-specific fragments (∼35 kDa) of IgG remained abundantly detectable within the cells till 48 h post-exposure (Fig. 1E). No significant differences in IgG entry and survival of Fc-specific IgG fragments were observed between different disease groups (Fig. 1F).
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@jnmaciuch My mistake, I must have misread something. All the groups IgG enter the endothelial cells. The only difference was it caused fragmentation in some patients cells.
 
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