Meshing the positive Rituximab treatment results with the GD-MCB hypothesis

[jenbooks]

Rich, as far as I know, it goes like this:

Bcells go through natural selection in the body. Even given the same stimulus exactly, they also seem to have some kind of internal tendencies, as to what role they will exactly play. In any case, in the IgM form they have five places to bind, they are rough and ready so to speak, in responding to an antigen. They bind to it but imperfectly. IE there are classes of bcells, ready to do their best, to bind roughly but strongly (five places) to an antigen. Then they these active bcells compete against each other, in successive generations in a form of evolution and natural selection, shuffling genes and refining binding until one emerges with a really really good fit.

The tcells approve that one to clonally expand. It goes into the bone marrow becoming a long lived plasma cell (I'm pretty sure--it's been over a month since I looked at this stuff).

It clonally expands, and at that point, your fever breaks, so to speak. You've got zillions of IgG antibodies, bcells generating antibodies in the dimer form, with a nearly exquisite specificity for the antigen. And you get over your flu and that bug never bugs you again.

Anyway, the plasma cells can regenerate the bcells, they are long lived, for at least ten years in the bone marrow.

So when you deplete circulating bcells, and the antibodies they made gradually fall away, you get temporary recovery from the CNS autoimmune disease known as ME/CFS. But eventually the plasma cells create a new generation of bcells.

Most of the time, at that point, the disease returns. And you have to re-treat.

Therefore, the idea that at that point, glutathione is normal because inflammation and oxidative stress is down, doesn't make sense to me.

I suggest before trying to fit it into or out of your theory, that you go and read a lot of Jonathan Edwards' work, and then Fluge & Mella's view--have you read the actual studies? If not you are free to email me and I can forward you some good stuff for you to chew your noggin' on.

It doesn't seem you may have delved into this enough, and into the history of bcell depletion and Rituximab, to necessarily understand all the details. Not trying to sound annoying at all...just trying to help.

 

[slayadragon]

>I guess that with your model I would be concerned that if the people who had biotoxin illness were re-exposed to biotoxins after their "recovery" from the Rituximab treatment, they would relapse.

Isn't that what we're seeing? I was under the impression that there was an assumption that eventually the Rituximab treatment would need to be repeated, as the B cells came back.

Maybe if people were living in good places and then got Rituximab, it wouldn't be as necessary to for them to get treated again. My guess is that the people who have been studied so far are in super-bad places, which is why they were desperate enough to be willing to get the drug -- and thus that it probably won't be a permanent cure for them.

The problem here is that the researchers looking into this aren't even asking the questions. If they were to do an ERMI test on people's houses to make sure they weren't terrible, perhaps there would be more of a chance that the gains on Rituximab would be permanent.

Doubtful that they'd want to do that though. It might ruin their study, if people moved and then made enough improvements that they no longer were desperate for the drug!

Best, Lisa

 

[richvank]

***Hi, Lisa.

During the past four years, I've interacted extensively with many dozens of people with classic ME/CFS. All of them have been skeptical about whether environmental biotoxins could be a factor for them. Some were just about convinced that they weren't. The only reason that they've been willing to talk to me is because nothing (including, with all due respect, your protocol) helped them enough to bring them back to anything approaching an acceptable life.

***O.K. It's possible that there was some self-selection involved here, which might bias the results of your informal "study."

For those who have been curious or committed enough to pursue it, EVERY SINGLE ONE has concluded that biotoxin reactivity is a factor for them. I'm not talking cause here. We need more information (such as a study looking at whether mold exposure is a risk factor for acquiring the illness) before we conclude that. I'm just suggesting that reactivity to the toxins is universal in the illness -- and thus, that any level of avoidance that people are able to pursue may be relevant to their ability to feel better and to benefit from treatment (such as the one that you favor).

***O.K. Again, there may have been some self-selection involved.

In terms of the measures you bring up, I agree that the visual contrast sensitivity test is not universally positive in this illness. As Shoemaker concedes, there are many false negatives to it.

***There might be some true negatives as well. Bear in mind that until recently, Ritchie has not wanted to concede that all cases of ME/CFS are not "his" cases, i.e., biotoxin illness cases. He's doing gene expression testing now to try to distinguish different types of cases, so we may be hearing more about this from him soon.

I myself had my own VCS go to normal within a couple of months after moving out of my moldy house, even though I still was quite sick with classic ME/CFS and still getting substantial biotoxin exposures. My own understanding is that biotoxin that is "loose" in the brain may affect vision and thus cause the person to fail the VCS, but that having toxin that is more tightly sequestered in the tissues (including other parts of the brain) still may have a general effect on immune functioning.

***I don't have any knowledge about possible different effects of "loose" or "sequestered" toxins. What is this based upon?

The ERMI test measures whether people are living in a blatantly moldy house. This is good for people to know, since no one -- and especially people who have CFS -- should be living or working in a moldy building. However, this has nothing to do with whether people have biotoxin illness, in terms of a) whether they are reacting to small amounts of biotoxin in their environments or b) whether they previously were exposed to moldy buildings. Once certain people have been made ill by mold, this illness does not go away just because they move out of the moldy place. Part of this illness is a hyperreactivity to various biotoxins -- ones that can be present in buildings (even ones that don't seem that bad on the ERMI), in the outside air, or on their contaminated possessions. In addition, this is a poisoning, not an allergy. For instance, if biotoxins are sequestered in the brain, this can affect cognition regardless of what current exposure is.

***O.K. The ERMI test can be very helpful, though, if a person has been living in a house that has a serious mold issue, and they don't know it.

Shoemaker's panel is extensive and takes skill to read. Just because (for instance) C4a happens to be low on a particular day does not mean that people do not have mold illness or even that they are not being exposed to large amounts of mold. Unfortunately, there is no one single measure that shows whether people have mold illness, which is why Shoemaker requires such a wide panel (costing more than $1k). I would be interested in seeing the panel results of people with severe ME/CFS that you cite as not having mold illness, therefore.

***That's a reasonable request, and I'd like to see lots of them! However, the very cost factor you noted makes it difficult to get this kind of data. People don't usually want to plunk down that much cash unless they have a very strong suspicion that they have biotoxin illness. I think Ritchie has data of this sort, but getting it out of him could be tough, because as I mentioned above, he is loathe to admit that such cases exist, although I think he is moving in that direction a little more now.

In terms of HLA DR, every single severely ill ME/CFS patient that I have encountered (and who has gotten the test) has one of the following genotypes as described by Shoemaker: 1) Multi-Susceptible (or Multi-Susceptible + Something Else), 2) Lyme Susceptible + Low MSH, 3) Mold Susceptible + Low MSH. This is the worst 5% of all genotypes, according to Shoemaker. (Of these severely ill sufferers, I would guess that a whopping 25% or so have Multi-Susceptible + Mold-Susceptible, Multi-Susceptible + Low MSH, or double Multi-Susceptible -- equal to about 1/4 of 1% of the population.) Of the moderately ill CFS patients I have encountered, some have the preceding genotypes, and some have specific other genotypes (Mold-Susceptible, Lyme-Susceptible or Low MSH). Again, many of these patients have no belief that mold is a factor for them and had the test performed either a) routinely by their regular CFS/Lyme doctors or b) out of desperation, because they felt like there was no other treatment possibility that might help available to them. I'm thus interested in the HLA DR types and the specific case histories of the "ME/CFS" patients that you have seen that you don't think are biotoxin illness patients.

***Well, I don't have a collection of them, though I do recall seeing some in the past. Very few of the people whose cases I have studied have run the HLA DR DQ typing panel. If I suspect from their history and symptoms that they may have biotoxin illness, I suggest that they or their physician consult with Ritchie. But in a lot of histories, there are other factors that appear to be causal, and I don't see anything suggesting biotoxin illness. And I have seen improvements in cases where no avoidance or cholestyramine treatment were involved.

Ever since the beginning of this illness, people have been dismissing biotoxins as "just one factor that only applies to some people." Certainly, we don't know for sure that it is relevant to everyone. Stating before we have the proper data that it _doesn't_ apply to everyone is being unscientific though.

***I agree. There really should be a good study of this. Ritchie may end up doing it. I'm hopeful that his gene expression work will shed light on this. He sounds pretty upbeat about it.

***Best regards,

***Rich

 

[richvank]

Hi, jenbooks.

It's true that I am not an immunological wizard! That is an area I need to go back to, among a few more! It's fascinating stuff, and it is continuing to develop rapidly.

Best regards,

Rich

 

[richvank]

>I guess that with your model I would be concerned that if the people who had biotoxin illness were re-exposed to biotoxins after their "recovery" from the Rituximab treatment, they would relapse.

Isn't that what we're seeing? I was under the impression that there was an assumption that eventually the Rituximab treatment would need to be repeated, as the B cells came back.

Maybe if people were living in good places and then got Rituximab, it wouldn't be as necessary to for them to get treated again. My guess is that the people who have been studied so far are in super-bad places, which is why they were desperate enough to be willing to get the drug -- and thus that it probably won't be a permanent cure for them.

The problem here is that the researchers looking into this aren't even asking the questions. If they were to do an ERMI test on people's houses to make sure they weren't terrible, perhaps there would be more of a chance that the gains on Rituximab would be permanent.

Doubtful that they'd want to do that though. It might ruin their study, if people moved and then made enough improvements that they no longer were desperate for the drug!

Best, Lisa

Hi, Lisa.

As I understand it, there were a small number of people who had what seemed like a permanent recovery. Of course, I don't know what their living environments were like, or whether they moved to better places after the treatment. These are good questions.

Best regards,

Rich

 

[slayadragon]

Hi Rich,

Yes, we definitely need studies looking at the propensity of ME/CFS sufferers to have biotoxin issues. I've been talking to Lenny Jason about the idea of working on this with him, and challenges (even if funding were to become available) are not in any way lacking.

Primary is the one that you keep bringing up with Shoemaker's patients: the idea that only someone who already suspected mold illness would go to him. Thus, we would need a sample of well-vetted, random CFS patients, such as the ones that were used for the XMRV studies. That means that ME/CFS doctors would have to participate, and persuade their patients to participate. Well, who knows, maybe I can figure out a way to make it happen.

The study that I am envisioning would look at whether living in a moldy home is a "risk factor" for getting ME/CFS. One thought is that this could involve taking patients who are living in the same homes where they initially got sick and doing ERMI tests. Probably we'd have to have matched controls (e.g. from the same city), since the ERMI is a national test and homes can vary in moldiness by region.

I'd also like to look at HLA DR because, as I say, it seems to be that this is extremely highly correlated with ME/CFS. Shoemaker, of course, already has done this, but his data is worth relatively little with regard to ME/CFS because he is a "mold doctor" and his sample thus is perceived to be biased. If we're going to try to show causality in ME/CFS, it needs to be a random sample of people, as you say.

Until such work (or other work) is done, I can't say conclusively that biotoxin issues are a factor for everyone with the illness. Nor can you say, based on the data that you are describing here, that biotoxin issues are not a factor for everyone with the illness.

Even if not all CFS patients have mold-susceptible genotypes and previous exposures to moldy buildings, they still conceivably could be mold responders (getting sick as a result of small mold exposures), due to some other factor. Unfortunately though, there aren't any tests yet to measure hyperreactivity (such as the kind that all the CFS patients that I have encountered demonstrate once they're unmasked). The C4a is not nearly responsive enough or accurate enough for that, it seems.

Just FYI, when I start talking to people about their histories, very very rarely is there anything that suggests to them or to anyone else biotoxin illness. (Sometimes I can see it, but only because I'm really familiar with this weird paradigm.) They always turn out to biotoxin responders anyway though, and to benefit from avoidance. Just because something doesn't seem obvious upfront doesn't mean that it doesn't exist!

My feeling (and you can tell me if this is conceptualizing it wrong) is that when people are getting active toxic exposures, they often have high levels of those toxins in the bloodstream. The body tries to deal with them as well as it can. If it can't process and eliminate them, then they get stored in the fat cells. If people then get out of a bad environment and clear what is in the blood, they still may have problems as a result of the toxins stored in the fat (including the fat in the brain). But I don't think those problems affect their vision specifically, because the vision dimming seems to be largely related to toxins in the bloodstream that get into the eyes/brain. (As sites go, the eye would seem to be the last place that an intelligent system would want to store toxins -- that is pretty delicate tissue and an especially important organ. So if the blood is clear of toxins, the eyes may seem unaffected even if the rest of the body is still having major problems.)

I'm not a medical scientist though (like Lenny Jason, my training is social psychology), so I could have it all wrong though.

It would be interesting to have your thoughts, especially on the proposed study designs.

Best, Lisa

 

[brenda]

Hi

Could anyone tell me please where the best place to have an ERMI mould test done from either the UK or US? I have become worse after living for 8 months in a home where black mould is growing on the window ledge.

 

[anciendaze]

This discussion has veered in a direction which highlights a misunderstanding of my earlier post here. I am not talking about too much or too little in the way of oxidative reactions in this illness, I am talking about misdirected responses. Even in healthy people these reactions are used to degrade malformed proteins. These molecules may be the result of innate defects in cell metabolism, environmental toxins or pathogens. Accumulation of undesirable biochemicals is common in this illness. Either they are coming in too rapidly or they are being eliminated too slowly. Even with evidence of too much oxidation patients still show elevated levels of a variety of substances healthy people eliminate quickly. One patient I know would have to live in a plastic bubble (of a suitable non-toxic plastic) to avoid environmental toxins. My conclusion is that she has a defect in the processes which eliminate toxins. Because she had a sudden onset, I would say that this is an acquired defect.

Because some malformed molecules may serve purposes in the life cycle of a pathogen these processes form part of the defense against pathogens. We have evidence of multiple low-grade viral infections in ME/CFS patients, except for cohorts where signs of viral infection have been used for exclusion. Some of these infections may be new pathogens and some may be reactivated ones. Destroying molecules vital to the life cycle of a pathogen is one way of holding it latent. In an extreme case oxidative reactions may destroy an entire defective cell, a last-ditch defense against disease.

There have repeatedly been reported parallels between immune dysfunction in cancer and ME/CFS

All of this fits a hypothesis about misdirected response.

 

[equestrian111]

I suggest emsl phone 8002203675 in nj, USA. You can order kit in there web site WWW.moldinspectionkit.com they give a very detailed analysis. Ugggg mine was not pretty.

 

[slayadragon]

BTW, from what I have heard, England has a real dearth of professionals who can properly deal with mold in the way that the knowledgeable professionals in the U.S. do. The only person that I have heard who seems really competent is Jeff Charlton in London (tech at 999team dot org).

If folks have other questions about mold, I suggest posting them on this section of the Phoenix Rising board.

http://forums.phoenixrising.me/foru...sing-Biotoxin-Chemical-and-Food-Sensitivities

Best, Lisa

 

[place]

all though I can't say I understand all or any of this but I can tell you that I think you will find your answer in the correlation between ALL of those solutions people have recovered. If there is none, than only the means that what got them into the situation will dictate how they will get out. When I look at the solutions it reminds me of detox all the junk out of the system and support the immunity via environment, supplements, pacing, ATP production to help move stuff along.

Personally I believe it is immunity issue. I have been sick my whole life. When "it" all started, I had moved into a moldy apartment with a 6.3' olympic swimmer. I had never ever had to share my queen size bed with anyone and I struggled with sleeping (and not for the good reasons=). So it started with two items that evolved into chronic sinus infections. Then into fibro.

My energy and feeling of sickness go from 2 (bad) to a 9 (great) in 5 seconds. How? I get the infection out of my Maxillaires by any means necessary. Its always a table spoon worth of green/yellow stuff.

Rituximab is only a temporary fix and our B cells are apart of the problem but its not the main problem or the main solution. However, Its a big beautiful piece of the puzzle!

Place