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Klimas London presentation, CD26/DPPIV impaired in CFS - retroviral involvement?


Senior Member

Hi, determined.

Thank you for tracking that down. I'm familiar with that paper, and discussed it with Kevin Maher when it was first reported. I think that was a real breakthrough in getting a better understanding of one of the ways the immune system is dysfunctional in ME/CFS. I told Nancy Klimas a few years ago that the GD-MCB hypothesis can account for all the observations her group has made with regard to the immune system, but I don't think she has been able to get hold of this yet. She and her group pretty much stay within the discipline of immunology, and don't venture to look into the underpinnings of the immune system in biochemistry. They do seem to be networking with others more now, though, which is a hopeful sign. This has pretty much been true of the other specialized ME/CFS researchers as well. There's the problem of the forest vs. the trees, or the elephant and the six men of Industan.

O.K., so it looks as though most of the available evidence (which is not terribly abundant!) is still consistent with my hypothesis about defective perforin synthesis due to glutathione depletion in the NK cells, so I'm going to hang onto it for now.

Based on Sushi's and Emootje's results, these poor cells are pushing hard, trying to make more perforin, but they just can't do it, and the mechanism I have suggested would explain why, as well as being consistent with many other aspects of ME/CFS.

The nefarious thing about the GD-MCB mechanism in ME/CFS is that it impacts the immune system in several ways which combine to subterfuge the ability of the immune system particularly to combat viruses, intracellular bacteria, and fungi, including yeasts. And of course, these are the types of infections we see in ME/CFS. In my view, the whole activated Rnase-L thing is there because the T cells are not able to come to the rescue, again because of glutathione depletion, which removes the "teeth" from the cytotoxic T-cells, but also because of depleted folate and thus inability to undergo rapid T-cell clonal proliferation in response to infections signalled by cytokines. The cytokines stay high, calling for help, but the T cells are not able to respond. Because the NK cells are also dysfunctional, for the same reason, the RNase-L system is left to fight the battle alone, and it is a blunt instrument, intended to be temporary.

A frustrating thing to me is that it seems obvious to me that the basic problems in ME/CFS are in the fundamental metabolism, but the researchers don't seem to want to look down there. Instead, they prefer to continue looking at the "higher level" aspects, which are actually downstream in the pathophysiology, in my opinion. Until the basic issue is dealt with, treatment of these higher order issues is going to produce only limited benefits.

Best regards,