Astounding Norwegian research breakthrough with Rituximab can solve CFS mystery!!!

[richvank]

Hi, all.

The more I read and hear from people, the more I believe that the role of Rituximab and other immune suppressants in ME/CFS is to lower the inflammation, and hence the oxidative stress, allowing glutathione to rise. If it rises enough to break the vicious circle involving the B12 functional deficiency, the partial methylation cycle block and the folate draining, the person recovers. If not, when the drug treatment wears off, down they go again. It has occurred to me, and some others have suggested this also, that doing methylation treatment while suppressing the immune system, at least somewhat, might help more people to achieve recovery. This is just a hypothesis, and would have to be entered upon very carefully, with supervision of a licensed physician. I would be leery of continuing to suppress such an important part of the immune system indefinitely.

I think that concluding from this study that ME/CFS is an autoimmune condition would be following a red herring. It could cause a lot of effort to be wasted in the wrong direction. That's just my opinion, and as always, I could be wrong.

Best regards,

Rich

 

[aquariusgirl]

I have a friend with an autistic son who has apparently made great gains by doing a year of IVIG followed by a year of steroids.
Presumably the steroids do what you are suggesting. They suppress the immune system, dampening inflammation.
Not recommending this therapy....just saying.

 

[Dreambirdie]

Pardon my scientific ignorance, but my general question is this:
If ME patients have already got low NK cells, and then they kill of a whole bunch of B cells with Rituxan, what happens over the long term to the immune system?

And since it is frequently the herpes family of virus that appears to be infecting the B cells (did I get that part right?) when they are active, what happens later, when the latent virus in the CNS pops back out to infect the new B cells? More Rituxan?

I feel a little frightened of killing off a whole segment of a compromised immune system--although it's not lost on me that that segment is itself infected with something bad.

I like the sound of that new antiviral Cort was talking about that appears to be able to go straight to the CNS--which is where a lot of the nasty buglets we contend with like to hang out (herpes, spirochetes.) It seems it is a non-toxic yet much stronger version of Vistide. (but that's OT on this thread.)

I like that an expensive chemo drug is bringing attention to the ME dilemma. I think that's the only way to gain traction; but big pharma does not always have the best interests of patients in mind, and the view of the disorders/treatments can be myopic. Still I think the best part of this study is the validation and attention from Medical World, and might signal the end of an era of abuse, neglect, and demeaning.

Me too, leela. Those are my questions and concerns as well (bolded).

When I had my B cells tested several years ago, I had only ONE THIRD the normal amount. SO I would not be willing to risk killing off more.

I am glad however, to see the attention the study is bringing to ME, though I would like to see MUCH MORE, especially on US media.

Maybe by signing this petition for an apology from our own government for neglecting ME patients, we can make that happen....
http://www.change.org/petitions/apologize-for-not-responding-appropriately-to-the-mecfs-epidemic

 

[klimt]

Rituximab B cells Enterovirus?

Hi everyone,

very interested to hear the discussion on a great study, good things to come I hope.

I'm new here but I have been following the forum for quite a while now. I had had a bad relapse and writing just hasn't been an option for me until now!
I was wondering what you thought of an enterovirus connection as I'm near convinced that this may be the cause of my ME and fibro. I got sick as a kid about 12 years ago with really bad gastroenteritis. It landed me in hospital twice in two months, for about six weeks in total and I have had severe stomach pains and aches since then. Things got really bad five years ago after a series of immunisations and I have been pretty much housebound with ME and fibro since then!

But this also seems to run in the family. My father has ulcerative colitis and epididymitis (hoping never to have that!) which get really bad if he overworks etc. and these are enteroviral in nature as far as I know. My mother has also been sick for most of her life but her main complaint is the stomach/gut but she also gets terrible throat infections every few months which knock her down for quite a while. While watching Dr. Chia's talk on the invest in M.E., he talked of a patients history (non ME) which seemed very similar and said an enterovirus was at play...

Anyway, I was thinking... not that I have done much research on it (brain won't allow), but do you guys think that an enterovirus might fit into the Rituximab story in any way???

In the limited search that I did, I came across an article which was on an enteroviral outbreak in China in 2008 and in it it stated that - "Comparisons between severe and mild cases demonstrated significant elevations of B cells and IgG levels and corresponding general decreases in natural killer (NK) cells and T lymphocytes in severe cases at the acute stage of infection (p < 0.01 for all)."

http://www.ncbi.nlm.nih.gov/pubmed/20950217

I had heard that B cells were elevated in the Rituximab patients and as I understand it NK cells are depleted in most ME patients...

Is it possible that an enterovirus could be at work that keeps the immune system on its toes, causing the B cells to increase and NK cells decrease??

I'm probably missing some very simple piece of information that suggests otherwise. But I would love to see what you guys think as I don't have the muster to figure it out by my onesie at the moment!

Many Thanks,

Best

 

[FancyMyBlood]

I think that concluding from this study that ME/CFS is an autoimmune condition would be following a red herring. It could cause a lot of effort to be wasted in the wrong direction. That's just my opinion, and as always, I could be wrong.

Best regards,

Rich

Hi Rich,

I have a different opinion. To me the autoimmune hypothesis sounds very plausible and it gives some very elegant explanations for the characteristics of this illness. It would explain the female:male ratio, it would explain the autoantibodies found in ME/CFS and it would also somewhat unify the viral/toxin origin with the psychological origin. I believe both can trigger an autoimmune condition.

 

[Tristen]

Hi, all.

The more I read and hear from people, the more I believe that the role of Rituximab and other immune suppressants in ME/CFS is to lower the inflammation, and hence the oxidative stress, allowing glutathione to rise. If it rises enough to break the vicious circle involving the B12 functional deficiency, the partial methylation cycle block and the folate draining, the person recovers. If not, when the drug treatment wears off, down they go again. It has occurred to me, and some others have suggested this also, that doing methylation treatment while suppressing the immune system, at least somewhat, might help more people to achieve recovery. This is just a hypothesis, and would have to be entered upon very carefully, with supervision of a licensed physician. I would be leery of continuing to suppress such an important part of the immune system indefinitely.

I think that concluding from this study that ME/CFS is an autoimmune condition would be following a red herring. It could cause a lot of effort to be wasted in the wrong direction. That's just my opinion, and as always, I could be wrong.

Best regards,

Rich

I agree not an "autoimmune disease". More like a component of me/cfs being autoimmune. And this seems true for some, but not all. Maybe it's a progression or a subtype issue.

 

[Jenny]

Hi, all.

The more I read and hear from people, the more I believe that the role of Rituximab and other immune suppressants in ME/CFS is to lower the inflammation, and hence the oxidative stress, allowing glutathione to rise. If it rises enough to break the vicious circle involving the B12 functional deficiency, the partial methylation cycle block and the folate draining, the person recovers. If not, when the drug treatment wears off, down they go again. It has occurred to me, and some others have suggested this also, that doing methylation treatment while suppressing the immune system, at least somewhat, might help more people to achieve recovery. This is just a hypothesis, and would have to be entered upon very carefully, with supervision of a licensed physician. I would be leery of continuing to suppress such an important part of the immune system indefinitely.

I think that concluding from this study that ME/CFS is an autoimmune condition would be following a red herring. It could cause a lot of effort to be wasted in the wrong direction. That's just my opinion, and as always, I could be wrong.

Best regards,

Rich

Hi Rich

We can always rely on you for thoughtful responses to new hypotheses!

FWIW I have very high levels of several neurologic antibodies, some of which apparently indicate neuro autoimmunity. Some autistic children have some of these too.

They are:

BBB Protein IgA, IgG and IgM
Myelin basic protein IgG and IgM
Neurofilament IgM

Any views on the relevance of these to anything?

Best wishes

Jenny

 

[Enid]

Don't at all believe in FancyMy Blood post 313 - nothing whatsoever to do with psychology. Howcome all this nonsense creeps back now. What all the mind again.....gee have I got a dickey personality.....bunk.

 

[SilverbladeTE]

Don't at all believe in FancyMy Blood post 313 - nothing whatsoever to do with psychology.

Agreed, sort of.

psychological stress can of course, worsen just about ANY health problem
Wessely's insane arrogance is in believing that that "false belief in an illness" can cause specific even lethal health problems, as opposed to low grade/long term worsening of things or, psychological problems leading to self harm (like anorexia, which now seems ot have a biological issue, too)

as opposed to

emotional distress worsening an ongoing autoimmune/infection problem (which seems the case with ME and completely NOT the same as what Wessely etc believe, and I've said such before)

hands up, how many of us have had a "bad day" after truamatic or just simply overpowering EMOTIONAL events, hm? lot of if not all of us I bet. And for us, "overpowering" cna merely be the normal issues of dealing with loved ones! :/

See how we react to multi-tasking, too many people etc. Same thing, it is NOT psychological, it's varied damage/inflammation of nervous system (akin to low grade menigitis) as underlying problem, and nasty feedback/over reaction to any "stressor" as some strange part of that (the body actively expecting/seeking stressors and reacting to them to prevent an infectiosu agent reahcing brain/heart, as it does with Flu liek bugs, hence much of our symptoms)
("stressor" is anything that stresses the body, from exercise to injury to strong emotions, *not* merely "emotional stress")

But same can be said for many other illnesses, ME I suspect has very strong over reaction to any indicators of stress ot the body : infection, injury, poison; emotional heck even metal exercise (hence I have problems with doing art projects, not jsut heaedaches etc getting in the way...literally thinking too much worsens my condition as it's exercise, brain uses huge amount of energy)

As research has shown, a broken heart is, for the sufferer, far more painful than about any bodily injury
it does not *itself* hower, cause specific, sudden, catastrophic disregulation/reaction of the body
Wessely put the freakin' cart before the horse, or rather, had the horse driving the cart, the blithering idiot!

 

[mellster]

Here's a hypothesis - I borrowed all of its elements from Rich and the other great researchers/scientists out there, and I don't know if it has been formulated as a whole like this:

Multiple (partially opportunistic, partially causative) chronic infections and other stressors bring down the body's defenses, with a definite involvement of one or many viruses that are capable of tricking body into a continued Th2 (extracellular) immune response while they infect one or many types of immune cells (e.g. B cells). This then will cause a ripple effect of hormonal (HPA axis)/vitamin/mineral deficiency/imbalance and methylation dysfunction causing a wide range of neurological and non-neurological symptoms.

Bringing down the viral load by either arming/modulating the immune system for a better Th1 response or using drugs with antiviral properties that knock out the virus and/or its infected cells will correct the Th2 imbalance since less viral load = less viral excretion tricking the body into a Th2 response and also calm down the entire immune response. Esp. when using immune modulators, a temporary increase in symptoms might be experienced, but in the long term this could be the favorable approach to drugs using the "sledgehammer" as it allows the body for continued self-healing - that is unless it is proven in the future that the auto-immune-response is stuck/chronic in the majority of patients, then continued use of targeted immune suppressors might be needed. Also methylation and hormonal support will likely be needed for a prolonged time.

This is obviously very simplified but I just wanted to throw it out there

 

[FancyMyBlood]

Don't at all believe in FancyMy Blood post 313 - nothing whatsoever to do with psychology. Howcome all this nonsense creeps back now. What all the mind again.

So you're denying that, at least in a subset of patients, ME/CFS symptoms appeared after a very stressful period?

I'm NOT saying it's all in the mind AT ALL. I'm saying the autoimmune hypothesis (which is by definition not in the mind) could unify the theories of different causes for ME/CFS. Some get ill after a viral infection and some after stressful periods. In the latter case a psychological cause is the trigger, but this doesn't mean ME/CFS is a psychological disorder at all. For example, in SLE (another autoimmune condition) some patients get so called 'flare-ups' after they experience a stressful event/period.

 

[mellster]

Agree with Fancy here - aggressive resting is believed to bring best relief, don't forget that resting does not only involve resting the body, it also allows the mind to calm down. Also, there is a difference between a psychological disorder (which CFS/ME most likely has nothing to do with) and psychosomatic/mental stress which has been proven to impact physical functioning of the body. That does not at all mean that you give into the harmful psycho-babble surrounding ME/CFS.

 

[Enid]

Stress is part of life for everyone - it is quite a normal thing in good health even (mentally/emotionally of course). But the stress we now discover is a pathology - let's keep it that way now we know more of the dysfunctions of the immune/neurological/endocrine systems. Oh and the viruses commonly found involved. Isn't this thread about Astounding Norwegian breakthrough (nothing to do with psychology as far as I can see).

 

[kurt]

We hear all the time in science that correlation is not cause. Well, reality is complicated, just found this interesting study about the correlation between autism and autoimmune conditions. The whole article is available free. Also, a brief search shows that the topic of autoimmune disease in autism is recent but there are significant studies already showing evidence. So maybe we have a new way to connect the dots now beween ME/CFS, Autism, and autoimmune diseases. What is the common connection here?

Pediatrics. 2009 Aug;124(2):687-94. Epub 2009 Jul 5.
Association of family history of autoimmune diseases and autism spectrum disorders.
Atladttir HO, Pedersen MG, Thorsen P, Mortensen PB, Deleuran B, Eaton WW, Parner ET.
Source
Nanea, Department of Epidemiology, Institute of Public Health, bNational Centre for Register-Based Research, and eInstitute of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark. hoa@soci.au.dk
Abstract
OBJECTIVES:
Recent studies suggest that familial autoimmunity plays a part in the pathogenesis of ASDs. In this study we investigated the association between family history of autoimmune diseases (ADs) and ASDs/infantile autism. We perform confirmatory analyses based on results from previous studies, as well as various explorative analyses.

METHODS:
The study cohort consisted of all of the children born in Denmark from 1993 through 2004 (689 196 children). Outcome data consisted of both inpatient and outpatient diagnoses reported to the Danish National Psychiatric Registry. Information on ADs in parents and siblings of the cohort members was obtained from the Danish National Hospital Register. The incidence rate ratio of autism was estimated by using log-linear Poisson regression.

RESULTS:
A total of 3325 children were diagnosed with ASDs, of which 1089 had an infantile autism diagnosis. Increased risk of ASDs was observed for children with a maternal history of rheumatoid arthritis and celiac disease. Also, increased risk of infantile autism was observed for children with a family history of type 1 diabetes.

CONCLUSIONS:
Associations regarding family history of type 1 diabetes and infantile autism and maternal history of rheumatoid arthritis and ASDs were confirmed from previous studies. A significant association between maternal history of celiac disease and ASDs was observed for the first time. The observed associations between familial autoimmunity and ASDs/infantile autism are probably attributable to a combination of a common genetic background and a possible prenatal antibody exposure or alteration in fetal environment during pregnancy.
see: http://www.ncbi.nlm.nih.gov/pubmed/19581261

One point that keeps nagging my brain is the common trigger of EBV for ME/CFS. Nearly everyone has EBV, but most people manage the virus. We often don't, and often also have CMV (the other HGV - Herpes Gama Virus). I've posted previously the NK cell connection, the NK cells help keep EBV from converting B cells. So whatever causes the low NK cytotoxicity, might that be our ultimate core pathology? If the NK can not keep EBV controlled and B cells get converted, there is higher risk of an autoimmune response, which creates oxidative stress. When this happens in a person with weak methylation, we get the MB-GD situation, mitochondria melt-down, etc. If this is our etiology, then killing off the B cells might not be the ultimate therapy, restoring NK cytotoxicity would be higher up in the chain of events that leads to the eventual MB-GD/mitochondria problem... sorry this is a bit cryptic, still thinking this through. Anyway this model resonates well with the fact that we now have three different therapies that significantly alter the course of ME/CFS, anti-virals (particularly those targeting EBV/CMV), methylation support, and now B cell depletion. IF the model of

NK=>EBV=>B-cell=>Autoantibody=>Oxidative Stress=>MB-GD=>Mito

is correct, then the divergent therapy success is explainable, each works on different areas of the etiology. Or not. Will be interesting to see who 'cracks' the ME/CFS model first, seems like we have our Rosetta stone now, thanks to the works of many (now incl. Mella/Fluge).

 

[mellster]

Kurt, I agree in this that if one has low or low normal NK cell count and/or cytotoxicity, then correcting this problem should probably be the first objective. There could be an ultimate core pathology or there could just be a vicious feedback cycle when multiple stressors hit you at the very same inconvenient time.

 

[leela]

aggressive resting

I love this! Best oxymoron EVER! I am going to borrow this, mellster, and use not only as a practice but as my answer when people ask me "And what do you do?"

 

[mellster]

Thx, feel free to use it although I have seen this used before and just adopted it

 

[kurt]

Kurt, I agree in this that if one has low or low normal NK cell count and/or cytotoxicity, then correcting this problem should probably be the first objective. There could be an ultimate core pathology or there could just be a vicious feedback cycle when multiple stressors hit you at the very same inconvenient time.

Good point. There is research showing a connection between stress and NK function. Stress might start a vicious circle, but the NK may be at the 'high point' or top of the circle, the lynch-pin, if that makes sense.

Incidentally, laughter is known to enhance NK function.

Altern Ther Health Med. 2003 Mar-Apr;9(2):38-45.
The effect of mirthful laughter on stress and natural killer cell activity.
Bennett MP, Zeller JM, Rosenberg L, McCann J.
Source
Indiana State University School of Nursing, Terre Haute, Ind., USA.
Abstract
CONTEXT:
A recent survey of rural Midwestern cancer patients revealed that humor was one of the most frequently used complementary therapies. Psychoneuroimmunology research suggests that, in addition to its established psychological benefits, humor may have physiological effects on immune functioning.

OBJECTIVE:
To determine the effect of laughter on self-reported stress and natural killer cell activity.

DESIGN:
Randomized, pre-post test with comparison group.

SETTING:
Indiana State University Sycamore Nursing Center, which is a nurse-managed community health clinic in a mid-sized, Midwestern city.

PARTICIPANTS:
33 healthy adult women.

INTERVENTION:
Experimental subjects viewed a humorous video while subjects in the distraction control group viewed a tourism video.

MAIN OUTCOME MEASURES:
Self-reported stress and arousal (Stress Arousal Check List), mirthful laughter (Humor Response Scale), and immune function (chromium release natural killer [NK] cell cytotoxicity assay).

RESULTS:
Stress decreased for subjects in the humor group, compared with those in the distraction group (U32 = 215.5; P = .004). Amount of mirthful laughter correlated with postintervention stress measures for persons in the humor group (r16 = -.655; P = .004). Subjects who scored greater than 25 on the humor response scale had increased immune function postintervention (t16 = 2.52 P = .037) and compared with the remaining participants (t32 = 32.1; P = .04). Humor response scale scores correlated with changes in NK cell activity (r16 = .744; P = 001).

CONCLUSION:
Laughter may reduce stress and improve NK cell activity. As low NK cell activity is linked to decreased disease resistance and increased morbidity in persons with cancer and HIV disease, laughter may be a useful cognitive-behavioral intervention.

(LOL is now a CBT for ME/CFS... LOL)

 

[beaker]

aggressive resting

I love this! Best oxymoron EVER! I am going to borrow this, mellster, and use not only as a practice but as my answer when people ask me "And what do you do?"

something that might interest you to know --

A.R.T. ( Agressive Rest Therapy ) was actually used somewhat and often talked about as treatment back in the 80s. Obviously it did not make anyone better, just kept them from getting worse. (mostly)

 

[Snow Leopard]

If ME patients have already got low NK cells, and then they kill of a whole bunch of B cells with Rituxan,
what happens over the long term to the immune system?

It is a good question and we don't really know what the long term effects of B-Cell suppression are - there are claims it doesn't affect the levels of immunoglobulins but I think that might only be for immunoglobulins for which the immune system is already sensitised to. There are suggestions (and in my opinion highly likely) that long term Ritxuximab use will result in a significantlyh higher rate of (malignant) cancer.