Rituximab in ME/CFS

I found this post by Rich Van Konyenburg very interesting. His theories based on there being a block in the methylation cycle in most people with CFS/ME, seems some of the most accurate research to date.

It also applies to me very much, as substances that enhance methylation, such as Sam-e, DMG and B12 shots etc, make a much more noticable difference in many aspects of my biochemistry, more than any of the myriad of supplements I’ve tried. This is his theory on why Rituximab likely helps in CFS.

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Proposed mechanism for Rituximab in ME/CFS
(By Rich Van Konyenburg)

I think this is a very interesting development, and I want to suggest what I think is going on when Rituximab is used to treat ME/CFS.

It will probably come as no surprise to those familiar with my history here that I will propose a mechanism that fits with the GD-MCB hypothesis for the pathophysiology of ME/CFS.

O.K., here it goes:

Based on the body of immunological studies that have been done in ME/CFS over quite a few years, we know that the immune system is dysfunctional in this disorder. In particular, it has a pronounced shift to the Th2 type of response, away from cell-mediated immunity.

The NK cells and the cytotoxic (CD8) killer-T cells are ineffective, partly because they are unable to produce enough perforin to punch holes in cells that are infected with viruses. Since this is the main mechanism normally used to knock out viral infections, these infections cannot be knocked out.

The immune system is forced to use its fall-back mechanisms, which are the humoral immune response (antibodies produced in Th2 by the B cells, which become plasma cells), and the interferon-induced mechanisms, including RNase-L.

These are less effective and are not able to completely knock out viral infections (The cell-mediated cavalry never arrives). This is the reason for the ongoing guerrilla war in the person’s body, with both the reactivated viruses which have been in the body in the latent state, and with new ones that come along and infect the person after the onset of ME/CFS

As has been noted, the B cells do produce proinflammatory cytokines, which of course promote inflammation. Because most PWCs also have a dysfunctional HPA axis, cortisol tends to be low, and the inflammation is allowed to intensify to a higher level than normal.

Note that one of the main features of inflammation is oxidative stress, because cells of the immune system produce oxidizing species to attack the body’s enemies. Oxidative stress is well-documented in ME/CFS, with perhaps 20 published papers reporting evidence of it now.

And those familiar with the body’s antioxidant system will know that when a state of oxidative stress is present, the antioxidant system is losing the battle between oxidants and antioxidants.

Those familiar will also know that glutathione is the basis of the antioxidant enzyme system in the body. So now we come to realize that in the subset of PWMEs/PWCs in whose bodies infection is a major aspect of their illness, we can expect that a major part of the oxidative stress, and hence a major part of the demand on glutathione, will be due to inflammation, which is being stimulated by the B cells in the overactive Th2 immune response.

O.K., so now we put in Rituximab, which kills the B cells. What happens?

Well, the inflammatory cytokines drop down, as does inflammation. This lowers the oxidative stress, taking a big demand off glutathione, which is then able to rise to at least some degree.

Aficionados of the GD-MCB hypothesis will immediately suspect that a big part of the symptomatology of ME/CFS will diminish, since the causes of a large fraction, perhaps the majority, of ME/CFS symptoms can be traced directly to the depletion of glutathione.

So voila! The patient feels better, until her/his B cells grow back, and the whole process repeats itself, making her/him miserable again. So we hit the patient with another dose of Rituximab, and she/he bounces back up, and so on. If we do succeed in permanently devastating the B cells, what happens in the longer term? Certainly they were there for a purpose. Will the body be adequately defended against its enemies in the future? I think that’s a big question.

The main point I want to make is that this treatment, like many others that have been used or proposed for ME/CFS, addresses a down-stream issue in the pathophysiology, and does not get to the root of the problem, which I believe (and have evidence to support this belief) is a vicious circle mechanism that includes glutathione depletion, a functional deficiency of vitamin B12, a partial block of methionine synthase in the methylation cycle, and draining of folates from the cells. So far, the only way it seems to be possible to break this vicious cycle is to lift the partial block in the methylation cycle with appropriate treatment that includes simultaneous use of active forms of folate and high dosage of forms of vitamin B12. Among other effects, this should rebalance the immune system, so that the B cells as well as the other components of the immune system will return to their normal functions. I do need to add that some other things will likely need to be done as well to help this process along, and which things will depend on the details of each case. But lifting the partial methylation cycle block is the fundamental thing that needs to be done.

I would welcome any criticisms of this proposed mechanism. As far as I can tell, everything fits together well.

If anyone wants to get more information on the GD-MCB hypothesis, I recommend watching the video at

http://iaomt.media.fnf.nu/2/skovde_2011_me_kroniskt_trotthetssyndrom/$%7Bweburl%7D

The slides from the talk are available there too, if you don’t want to hang in for the whole 3-plus hours.

Best regards,

Rich
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