Rituximab Phase III - Negative result

[pibee]

I couldn't remember if you had 7 or 8 positives. From the small sample size that I am gathering of people who have done Cell Trend testing, either from PR or other groups, my anecdotal results are that the people who are positive for Cell Trend Abs, are also positive for other autoantibodies, such as Mayo, Cunningham Panel, etc. Vs. the people who were completely negative on 9/9 Cell Trend Abs, were negative on all Abs, including common ones like the Hashi's Abs. So it seems like the Cell Trend tests are positive in those who already meet an autoimmune profile (vs. it meaning that every single person with positives has POTS). But like I said, this is just anecdotal so far.
.

I dont have POTS. I did only ENA, ANA, thyroid (anti-tg, anti TPO) and CellTrend. I am positive for SS-A (my aunt and sister too, have Sjogren), anti-TPO (Hashimoto, again mom, sister and me) and 8/9 CellTrend, all except beta1. I didn't do Cunningham panel because expensive and also latest research says doing it via European lab is not reliable, but if anything I'd expect to have that positive because I fit PANS since childhood and antibiotics reduced OCD and anxiety symptoms in me.

Do you test positive for anti NMDA, or other brain autoantibodies, besides Cell Trend?

.

I will find out results in a week. Not sure if I want positive or negative result. Both sucks.

 

[PinkPanda]

I read about a few people with hashimoto antibodies now, and in addition histamine problems or MCAS.

I have high hashimoto antibodies, mildly elevated ANA, histamine intolerance (and leaky gut syndrome and 'Adrenal Fatigue'). My hashimoto is inactive though and TSH is in norm so I'm not taking anything to treat it.

I find it interesting that there seem to be some common factors in a group of people, maybe this could indicate an autoimmune subtype, where autoimmunity causes ME/CFS?

 

[Learner1]

Just catching up here as I've been traveling, but this has been an interesting discussion. This might seem random as I pick up various threads...

Jarred Younger found an autoimmune subtype. Mark Davis suggested it could be autoimmune. My ME/CFS specialist, after collecting my history went looking for other forms of autoimmunity, explaining, if you already have one autoimmune problem, its likely you have a genetic tendency to develop others.

Younger also found an infection subset. And, when I asked him if patients could have autoimmunity and infections, he said "Absolutely."

Someone wrote earlier about IGG levels and autoimmunity, with the idea that if one has low IGG, one can't have autoimmunity. This is not the case for some of us. I had low IGG, a tendency to infections, and several autoimmune problems. My ME/CFS doctor describes it as a dysfunctional immune system, which likely many of us have. Though some only may have an under or an overactive immune system.

The link regarding IVIG not helping ME/CFS is disappointing. What criteria was used to select patients? IVIG is helping many of us. However, its difficult to qualify, as these studies have been used to set criteria for insurance companies, where chronic fatigue syndrome is excluded as a qualifying condition. This is unfortunate as some patients who might benefit can't get it. Fortunately, my ME/CFS doctor was able to qualify me based on other criteria.

We are all different.

We have different genes, history of infections, nutritional and biochemical and immune status, levels of toxicity, diets, social situations, etc. The metabalomics studies have shown subsets of similarities among the many markers, but large variations in others.

The discussion of ICC vs. CCC vs. Fukuda illustrates this as well. We have some glaring similarities, but we don't all match. And the list of symptoms goes across multiple organ systems and represents a huge amount of biochemical complexity. Its ridiculous to think one solution will fix all of us.

While I wish there were a magic bullet, and am wondering if I still might fit into the Rituximab responder subset, I think its far more likely that we have a heterogeneous set of problems that need a sharp set of tools for astute doctors to use to snap us out of this. Or rather, gradually pull us out of this. We are not there yet.

But this has been one of the best discussions I've seen on this site in a long time, and I have faith that we can collect the rough tools we have, continue to gather formal and informal data, and eventually build the ideal toll set to tackle these diverse and vexing problems.

 

[Joolz]

Thanks. Non responder. No effect whatsoever.

Crap. Sorry to hear.

I was one of the participants who received placebo.

Obviously, I was devastated when I got the phone call / letter with the negative result of the study some weeks ago.

 

[bertiedog]

We have different genes, history of infections, nutritional and biochemical and immune status, levels of toxicity, diets, social situations, etc. The metabalomics studies have shown subsets of similarities among the many markers, but large variations in others.

I absolutely agree with you here, I have never believed there will be a magic bullet although its very obvious that people would like one. I think there are many layers to the lines and we have to peel them away one by one which is what I think Dr Myhill does and it works for many of her patients (according to her) but she admits it doesn't work for all but she does still go looking and seems quite open minded taking on board the role of infections, viruses, autoimmunity, hormones, diet, and environmental factors too.

I watched one of her You Tube videos recently and I couldn't help but be impressed by the fact she covered all known aspects and she does take note of the latest research. There wasn't anything I saw that I could disagree with and the only criticism is of course that this sort of treatment and sharing of information with a knowledgeable doctor who can actually prescribe a drug if indicated, isn't available to the majority of patients here in the UK. This just shows that if you want to feel better and get some professional help you have to have some money to throw at it to get some testing done with the sort of tests that aren't available on the NHS.

I have been very fortunate that I could do this and therefore my basic condition has been helped to the extent I average over 8000 steps daily but without that help I received (nothing from the NHS to get me on the path to improvement) I don't honestly know how I would have survived because I was so ill and spent most of my time housebound in 2000/2001, I also think that subsets are definitely to be found and wonder if this could be one of the reasons that we had such trouble on this Forum recently?

Pam

 

[ljimbo423]

I have been very fortunate that I could do this and therefore my basic condition has been helped to the extent I average over 8000 steps daily

Hi Pam- According to Mr. Google, that's about 4 miles a day!

Jim

 

[bertiedog]

Hi Pam- According to Mr. Google, that's about 4 miles a day!

Actually I think that is a bit of an exaggeration. I wear a Garmin Viofit device and the App it links to reckons that for instance on Tuesday this week I did 8618 steps which the App says was 3 1/2 miles and yesterday was 3.15 miles which I know sounds a lot but it is very much spread out through the day and evening when I might even manage a short dance round my living room whilst I am playing music and doing a jigsaw puzzle! But this doesn't happen every night for sure, sometimes I just lie down all evening doing nothing more than watch TV and dozing trying to recover. Also on many days I wouldn't be able to do this and the quick dance round the room never happens in the day, it take till about 10 am before I have got sufficient energy to do anything that is physical.

If I didn't pace my activities I wouldn't be able to do a fraction of what I do and when I have a virus the steps drop right back to maybe only 4500. I know this only too well having had 2 different viruses in the past week!

Pam

 

[neweimear]

Actually I think that is a bit of an exaggeration. I wear a Garmin Viofit device and the App it links to reckons that for instance on Tuesday this week I did 8618 steps which the App says was 3 1/2 miles and yesterday was 3.15 miles which I know sounds a lot but it is very much spread out through the day and evening when I might even manage a short dance round my living room whilst I am playing music and doing a jigsaw puzzle! But this doesn't happen every night for sure, sometimes I just lie down all evening doing nothing more than watch TV and dozing trying to recover. Also on many days I wouldn't be able to do this and the quick dance round the room never happens in the day, it take till about 10 am before I have got sufficient energy to do anything that is physical.

If I didn't pace my activities I wouldn't be able to do a fraction of what I do and when I have a virus the steps drop right back to maybe only 4500. I know this only too well having had 2 different viruses in the past week!

Pam

What treatments helped you Pam?

 

[Learner1]

There's also been a lot of discussion around if we all don't have the same problems which match all known criteria, then we can't possibly have ME or CFS or both. There was an insinuation that other diseases had more homogeneity.

This is false. There are different causes/sets of symptoms/states of biochemistry and damage/treatments/responses to diseases like Parkinson's, MS, cancers, and many others. In performing a differential diagnosis, doctors go according to symptoms and lab tests, grouping people with different genes, health histories, levels of toxicity, and comorbidities into convenient groupings so they can apply some drug that's gone through clinical trials with varying levels of success.

Here, it's not particularly productive to boot people out of our little club if they're not a perfect match for our own favorite symptoms. What would be productive is to collect data on genetics, mitochondrial function, toxicity, nutrient status, immune system status, microbiome composition, comorbidties, and treatments tried, and then come up with some algorithm to sift through it, and come up with some analysis of the driving issues, predictions for what try, and then trialing these solution sets on each targeted subset.

I've watched repeatedly as the same sledgehammers have been applied to Parkinsons, depression and anxiety, and cancers, with wildly unpredictable results due to these individual differences, and am reminded that people die every day from medications taken as prescribed by their doctors.

We are still in the Dark Ages on many fronts. There are some common problems here, with switches that need to be turned on, but we need solutions that account for our individual idiosyncrasies to increase our individual odds of success.

 

[Londinium]

I read about a few people with hashimoto antibodies now, and in addition histamine problems or MCAS.

I find it interesting that there seem to be some common factors in a group of people, maybe this could indicate an autoimmune subtype, where autoimmunity causes ME/CFS?

AFAIK, I have neither - but a sister with Hashimoto’s and a half brother with a rare mast cell disorder that almost killed him in the three years it took to get a diagnosis. This, plus a history on that side of the family that includes rheumatoid arthritis and fatal pernicious anaemia, is what convinces me what I have is highly likely to be autoimmune in nature - and the RituxME result isn’t enough to cause me to question that belief just yet.

 

[bertiedog]

What treatments helped you Pam?

Firstly it was getting my thyroid and adrenals treated, I needed medication for both these major problems but the NHS wouldn't help. I had 24 hour saliva cortisol/DHEA test done and blood tests for thyroid which were abnormal. About 10 months before this I had found out that I had high levels of mercury in my hair and in my blood so gradually had all 13 amalgams removed and over the next 2 years chelated it out as per Andy Cutler. It took over 5 years for the levels to get back to normal. Last time I was tested I still have Nickel over the range and will have to get it checked again to see if its back to normal.

During 2007 I learned about the mitochondria and had Dr Myhill's ATP test done showing only 48% ATP whereas it should have been more than 60 and it was rapidly used up during the test. There were blockages in the Translocation Test, first time round it was a virus and when done about 4 years later nickel showed up again.

I started supporting my mito with things like very high dose magnesium, various minerals to help with my detoxification issues, Fish Oil, GLA, Co Q10 and the active B Vits. I knew I had a high need for folate but I cannot tolerate it in supplements because it gives me awful migraines but I now have a diet high in natural folates so that is sufficient hopefully.

Since then I have had my genetics done through 23andme and it explains why I have had the build up of toxic metals and also tests have shown high levels of things like PCBs, I don't posses one of the major enzymes for detoxification, GSTM1 and have loads of other SNPs that make detoxification of heavy metals and some drugs/compounds very difficult. My genetics explain why I had a stillborn baby in 1973 linked to Spina Bifida and also why there is so much cancer in my family. I am just grateful I found out about all this so at least I can support my body with various targeted supplements but without the testing I wouldn't have known exactly where the problems were.

I have just had Genova's Organic Comprehensive Profile done so see what is exactly happening with the metabolites and hope to see some improvements from when I last had an Organic Acids test done in 2013.

The other major thing that has helped me was getting an oxygen concentrator about 5 years ago when I had autonomic testing done at Breakspear here in the UK. It showed that at that time I only had 50% of the normal oxygen at cellular level. Nothing wrong with my lungs, they are fine but I had this issue of poor oxygen and also high CO2 and was told this was very bad for me and I needed to breath oxygen from a concentrator for up to an hour at a time and could do this 3 times daily. I should say that I was at my worst for that test because I had gone for a swim only about 3 hours before the test and was absolutely worn out at the time of the test not having recovered at all but I suppose that was a good thing to do because it showed up a massive problem with how poor my oxygen was at cellular level.

It made a really big difference to how I felt and as time has gone on I only use it for about 20 minutes at a time and 30 if a bad day. It puts back energy into my body that I have used up.

I have also taken many different herbal products as I was diagnosed with Lyme and borrelia but I am still not sure if this was valid or not but the herbal tinctures definitely helped me to improve for at least a period of time but usually during winter because of the viruses I would pick up so easily my health would drop back.

Finally I should mention I have been very strict over my diet, eating low carb but lots of veg, nuts/seeds, some dairy, small amounts of meat and fish and as mentioned previously since September have started taking specific probiotics and beneficial fibres like acacia, psyllium and chia to try and feed the good bacteria that I am so short of as per Ken's suggestions at CFS Recovery.

Hope this helps.

Pam

 

[Martin aka paused||M.E.]

There's also been a lot of discussion around if we all don't have the same problems which match all known criteria, then we can't possibly have ME or CFS or both. There was an insinuation that other diseases had more homogeneity.

This is false.

Exactly.

You think that it would be productive "to collect data on genetics, mitochondrial function, (...) and then come up with some algorithm to sift through it, and come up with some analysis of the driving issues, predictions for what try, and then trialing these solution sets on each targeted subset." But that's what happens in Stanford and this Lipkin Study, isn't it? Or do you mean we on PR could help with it?

Sometimes I think it would be interesting if we could launch a big PR survey about symptoms and successful treatments... maybe there are patterns to be found just among PR users ...

 

[fingers2022]

Are we surprised?
If I understand it, rituximab is based on a theory of autoimmune disease.
Anyone who has ME knows that this is not autoimmune.
The immune system is fucked, not overactive...just like in AIDS.

 

[JES]

Are we surprised?
If I understand it, rituximab is based on a theory of autoimmune disease.
Anyone who has ME knows that this is not autoimmune.
The immune system is fucked, not overactive...just like in AIDS.

In fact we don't know what causes ME, nobody knows. And saying CFS is just like AIDS is factually wrong. AIDS patients tend to die due to secondary infections if the disease is left untreated. CFS patients (with a few exceptions) don't die, they survive for centuries even when their condition is miserable. Many CFS patients actually report they have never caught a cold after they got CFS, so the immune system is not fucked in that sense.

 

[Learner1]

Are we surprised?
If I understand it, rituximab is based on a theory of autoimmune disease.
Anyone who has ME knows that this is not autoimmune.
The immune system is fucked, not overactive...just like in AIDS.

Many doctors and researchers think there's an autoimmune component. It was discussed at the OMF Symposium by Mark Davis, Jonas Bergquist, and others and Jarred Younger found a subset with autoimmunity.

My ME/CFS doctor has a long history of treating HIV/AIDS patients and I'm finding his insights into dysfunctional immune systems to be very helpful.

Most of the research seems to indicate there's something very wrong with our immune systems, with a lot of collateral damage along the way.

 

[fingers2022]

In fact we don't know what causes ME, nobody knows. And saying CFS is just like AIDS is factually wrong. AIDS patients tend to die due to secondary infections if the disease is left untreated. CFS patients (with a few exceptions) don't die, they survive for centuries even when their condition is miserable. Many CFS patients actually report they have never caught a cold after they got CFS, so the immune system is not fucked in that sense.

Did I say 'CFS is just like AIDS'?
Don't think so.
I said the immune system effects are like in AIDS....re read my post please?
Autoimmune is not a cause...it's an effect...as a theory it is fucking useless.
Sorry, but there is a lot of research which shows that expletives are good for the immune system.

ME (not CFS...that's a very unhelpful name) is also characterised by secondary infections.
Colds...now that is interesting...it is our immune system that makes us feel like shit when we have a cold. If the immune system isn't working we might just feel vaguely unwell and not really functioning for a long time.

 

[fingers2022]

Many doctors and researchers think there's an autoimmune component. It was discussed at the OMF Symposium by Mark Davis, Jonas Bergquist, and others and Jarred Younger found a subset with autoimmunity.

My ME/CFS doctor has a long history of treating HIV/AIDS patients and I'm finding his insights into dysfunctional immune systems to be very helpful.

Most of the research seems to indicate there's something very wrong with our immune systems, with a lot of collateral damage along the way.

has anyone defined autoimmunity?
AIDS is caused by a retrovirus...duh

 

[Learner1]

has anyone defined autoimmunity?

From Medicine Net:

Autoimmunity: A misdirected immune response that occurs when the immune system goes awry and attacks the body itself.

Autoimmunity is present to some extent in everyone and is usually harmless. However, autoimmunity can cause a broad range of human illnesses, known collectively as autoimmune diseases.

Autoimmune diseases occur when there is progression from benign autoimmunity to pathogenic autoimmunity. This progression is determined by genetic influences as well as environmental triggers.

Autoimmunity is evidenced by the presence of autoantibodies (antibodies directed against the person who produced them) and T cells that are reactive with host antigens.

From Wikipedia:

Immunodeficiency and autoimmunity

There are a large number of immunodeficiency syndromes that present clinical and laboratory characteristics of autoimmunity. The decreased ability of the immune system to clear infections in these patients may be responsible for causing autoimmunity through perpetual immune system activation.

One example is common variable immunodeficiency (CVID) where multiple autoimmune diseases are seen, e.g.: inflammatory bowel disease, autoimmune thrombocytopenia and autoimmune thyroid disease.

AIDS is caused by a retrovirus...duh

From Wikipedia:

Human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV).

Following initial infection, a person may not notice any symptoms or may experience a brief period of influenza-like illness.

Typically, this is followed by a prolonged period with no symptoms. As the infection progresses, it interferes more with the immune system, increasing the risk of common infections like tuberculosis, as well as other opportunistic infections, and tumors that rarely affect people who have working immune systems. These late symptoms of infection are referred to as acquired immunodeficiency syndrome (AIDS)

A doctor who is familiar with immunodeficiency syndromes and opportunistic infections which can cause autoimmunity may be well-versed in the mechanisms that may help us.

Better than your GP.

 

[Martin aka paused||M.E.]

@fingers I don't really get your point. In many cases of ME there is a immune deficiency. And you can see that in the blood. And theoretically these patients can also die from it: Infections like systematic candida or clostridium difficile are very dangerous when you have a immune deficiency. So are many others... I think why ME patients with immune deficiency don't get as much dangerous infections as AIDS patients is because we are house or even bed bound! Where should these little nasty viruses and bacteria come from?

But what I think makes really sense is your theory that autoimmunity is not a cause but a an effect. Scientists now find that the microbiome in the gut, if it's "out of control" because you have a serious dysbiosis, can lead to autoimmunity. But even if it's only an effect, immunosuppressant drugs help... while it's not treating the cause of ME. So yes, I would find that surprising that the phase III study failed if these patients are in the immune deficiency subgroup!

 

[Gingergrrl]

So are many others... I think why ME patients with immune deficiency don't get as much dangerous infections as AIDS patients is because we are house or even bed bound!

I've heard many people say this as a theory (that people with ME don't get sick b/c they do not leave the house and are not exposed) but in my case, nothing could be further from the truth. I am not certain that I am in an ME sub-group, or a different illness, but I have not gotten a cold, flu or traditional illness in almost five years. During that time I was exposed to my (step) daughter, my niece, and other family members while they were sick, including while they had strep throat and all kinds of infections. Even though I use a wheelchair, I was never home-bound and I was at schools, hospitals, grocery stores, restaurants, taking my dog to the vet, etc. I was exposed to everything under the sun (even when my niece had scarlet fever) and I have caught nothing. Not even after Rituximab and technically being immunocompromised.

But what I think makes really sense is your theory that autoimmunity is not a cause but a an effect.

This makes sense to me that auto-immunity is the effect not the cause (and I think that is true in all autoimmune diseases but I could be wrong)? Even in Hashimoto's, I think my Endo said that a virus or something initially attacked my thyroid before it turned autoimmune? I started off with viral and mold exposure which, from my understanding, shifted into autoimmune chaos.

But even if it's only an effect, immunosuppressant drugs help...

That is my experience as well but I think it is the combination of an immune modulator (IVIG) and Rituximab that has helped in my case. But I will never be able to separate the two to know for sure.