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

[Paul Watton]

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

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.

 

[Jonathan Edwards]

Two things to note:
1. It was the antigen / antibody immune complex which was exposed to the cultured cell lines, not just IgG.

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.

 

[jnmaciuch]

1. It was the antigen / antibody immune complex which was exposed to the cultured cell lines, not just IgG.

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.

2. The IgG immune complex was selectively taken up by HUVEC cells but not Human Foreskin Fibroblasts.

Yes, as I already noted, it could be a cell-type specific effect. And per your last point:

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.

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.