The link doesn't seem to be working, or at least for me...
Who is more likely to gain improvements/remission from Rituximab?
- Thread starter kiwigirl29
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The link doesn't seem to be working, or at least for me...
Hip
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That's something I think you would have to test in a study. I am not sure where @kiwigirl29 got her info about this.
Would you have a link to that info by any chance?
AndyPR
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Don't know why, works for me, sorry.
ScottTriGuy
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Me either:
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AndyPR
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Pass. For whatever reason it looks like your browser has issues with Cort's website. I'm using the latest version of Firefox and it's happy with the site, why it should be different for anybody else I don't know, sorry.
ScottTriGuy
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More mysterious web weirdness.
Jonathan Edwards
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It may the other way around. 'Catching' a cold is mostly showing an immune response to the virus. The symptoms of a cold are chiefly caused by your immune system responding, not the virus being there. So not catching colds is not particularly likely to be a sign of an 'active immune system'.
I honestly do not think that the concept of an immune system being 'up' or 'down' is of any use to us.
AndyPR
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Jo Best
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Hello @kiwigirl29, responding in haste as am about to log offline, saw this posted today by Invest in ME Research about their international conference, not rituximab-related as far as I know, but hopefully of interest if you are in NZ - http://investinme.eu/IIMEC12-news-170204.shtml
I’m a little obsessed with the question of who might respond to rituximab because of strong autoimmune family history and some antibodies all of my own. My understanding is that Fluge and Mella think that there’s an autoimmune subgroup of ME/CFS patients who may potentially benefit. This quote is from the “Metabolic profiling indicates impaired pyruvate dehydrogenase function” paper: “Our previous findings in interventional clinical trials evaluating B lymphocyte depletion therapy, using the monoclonal anti-CD20 antibody rituximab, suggest that ME/CFS in a subgroup of patients could be a variant of an autoimmune disease (38–40), possibly involving antibodies.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161229/
Fluge and Mella collaborated with German researchers in a study with Norwegian and German patients looking at more closely at antibodies (Loebel et al 2015 link below). The Norwegian patients were in the rituximab trial so they were able to begin to piece together some antibodies that may be at play. Loebel et al say “We provide evidence that 29.5% of patients with CFS had elevated antibodies against one or more M acetylcholine and b adrenergic receptors which are potential biomarkers for response to B-cell depleting therapy.” https://www.ncbi.nlm.nih.gov/pubmed/26399744 (free full access when you click through).
They also make an interesting point that regular testing won’t pick up these antibodies:
“Our observation of a decrease of M and b receptor autoantibodies in patients responding to rituximab, in whom levels pre-treatment were within the normal range of control subjects, suggests that we may miss functionally pathogenic antibodies by just assessing quantitative levels by ELISA.”
I got more than a little excited when they mentioned that they found a correlation between the antibodies that may make a person a candidate for rituximab and elevated ANA and TPO antibodies (among other immunological measures, p.36-7) because I have them. Woo hoo! Abnormalities that may be good for something!
Loebel et al do mention chronic immune activation, firstly to highlight immunological irregularities that form part of the evidence that hints at a possible autoimmune pathophysiology (I think):
In the abstract Loebel et al say “Infection-triggered disease onset, chronic immune activation and autonomic dysregulation in CFS point to an autoimmune disease directed against neurotransmitter receptors.” In the paper they talk a good bit about T cell activation, which they defined as HLA-DR high CD8+ T cells >30%), and they were also interested in diminished C3c levels (<900 mg/l), or elevated TPO (>35 kU/l)/TG (>100 kU/l) antibodies, or elevated ANA titres (>1:160). My understanding is that they may be using the term “chronic immune activation” to refer to all of those – perhaps @Jonathan Edwards would be able to shed light on whether that’s feasible?
I suspect susceptibility to infections won't correlate with response to rituximab. I haven’t come across any convincing evidence correlating autoimmunity with whether a person does or doesn’t get infections. My autoimmune family members get infections. When I was milder and still able to work I did notice that I rarely picked up infections despite plenty of exposure, including working in a hospital, whereas before ME if a cold or norovirus worked its way through the hospital or my department, I generally got it. The odd infection that got through presented oddly too, I’d start off mildly ill and then get worse, and worse, and worse, rather than a few bad days followed by a gradual improvement. I’m housebound now so have very little exposure to infections, but when I do get a cold, it often gets worse over time.
Here’s to being major responders! (You know, if phase III trials work out.)
Fluge and Mella collaborated with German researchers in a study with Norwegian and German patients looking at more closely at antibodies (Loebel et al 2015 link below). The Norwegian patients were in the rituximab trial so they were able to begin to piece together some antibodies that may be at play. Loebel et al say “We provide evidence that 29.5% of patients with CFS had elevated antibodies against one or more M acetylcholine and b adrenergic receptors which are potential biomarkers for response to B-cell depleting therapy.” https://www.ncbi.nlm.nih.gov/pubmed/26399744 (free full access when you click through).
They also make an interesting point that regular testing won’t pick up these antibodies:
“Our observation of a decrease of M and b receptor autoantibodies in patients responding to rituximab, in whom levels pre-treatment were within the normal range of control subjects, suggests that we may miss functionally pathogenic antibodies by just assessing quantitative levels by ELISA.”
I got more than a little excited when they mentioned that they found a correlation between the antibodies that may make a person a candidate for rituximab and elevated ANA and TPO antibodies (among other immunological measures, p.36-7) because I have them. Woo hoo! Abnormalities that may be good for something!
Loebel et al do mention chronic immune activation, firstly to highlight immunological irregularities that form part of the evidence that hints at a possible autoimmune pathophysiology (I think):
In the abstract Loebel et al say “Infection-triggered disease onset, chronic immune activation and autonomic dysregulation in CFS point to an autoimmune disease directed against neurotransmitter receptors.” In the paper they talk a good bit about T cell activation, which they defined as HLA-DR high CD8+ T cells >30%), and they were also interested in diminished C3c levels (<900 mg/l), or elevated TPO (>35 kU/l)/TG (>100 kU/l) antibodies, or elevated ANA titres (>1:160). My understanding is that they may be using the term “chronic immune activation” to refer to all of those – perhaps @Jonathan Edwards would be able to shed light on whether that’s feasible?
I suspect susceptibility to infections won't correlate with response to rituximab. I haven’t come across any convincing evidence correlating autoimmunity with whether a person does or doesn’t get infections. My autoimmune family members get infections. When I was milder and still able to work I did notice that I rarely picked up infections despite plenty of exposure, including working in a hospital, whereas before ME if a cold or norovirus worked its way through the hospital or my department, I generally got it. The odd infection that got through presented oddly too, I’d start off mildly ill and then get worse, and worse, and worse, rather than a few bad days followed by a gradual improvement. I’m housebound now so have very little exposure to infections, but when I do get a cold, it often gets worse over time.
Here’s to being major responders! (You know, if phase III trials work out.)
Looks like they are taking a lot of angles on this awful illness!
Jonathan Edwards
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I don't really buy the argument in the quoted sentence. Infective triggers do not suggest autoimmunity. And I am not sure what they are referring by immune activation. What they are trying to home in on is, however, an interesting and reasonable idea. The suggestion is that antibodies to certain receptors involved in the autonomic nervous system and also present on B and T cells may be involved. The trick would be that the antibodies not only affected vascular regulation but fed back on to antibody producing cells to encourage the making of more antibody. That is very much in line with the way I personally think autoimmune states work.
To be honest I think the quoted sentence is rather a broad brush introductory remark that is not worth putting too much weight on. What is of interest is the idea of activation of specific cell populations. These may actually have a negative feedback effect on other cells so there is no general 'immune activation' involved.
Gingergrrl
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@KME Thanks for posting those quotes! My feeling is that people who have the M & B autoantibodies and those Aut-Abs are the cause of their symptoms (whether or not they have ME/CFS per se) will be responders to RTX or B-Cell depleting therapy.
I am exactly the same and also have an elevated ANA and TPO antibodies.
This is my own theory but I think it is the combination of having the autoantibodies PLUS not getting infections which makes someone a potential candidate for RTX. I have a very close friend with lupus who tried RTX many years ago but it did not help her. However, she is in the group of people who is constantly getting sick with colds, flu, and even recently got shingles out of the blue. So even though she is autoimmune, she still gets sick constantly. I suspect the autoimmune group who also does NOT ever get sick, will be the potential responders.
Thanks for clarifying, @Jonathan Edwards. I agree, I think that sentence is just an introductory remark. To me, it would make more sense if they had said that X, Y and Z point to immune dysregulation, but not necessarily autoimmunity. I’ll leave the poor sentence alone – I don’t think it has much to give, whereas the paper does.
I really liked your explanation of this:
Is it possible that a person could have some antibodies to these receptors long before ME appears, causing either no or minimal/subclinical symptoms, as a kind of predisposing factor, and that a triggering infection could then cause the feedback system to go a little awry, leading to pathological antibody levels and a clinically obvious disease?
This makes a lot of sense to me:
So there is specific immune activation, which due to negative feedback on cells outside of that specific population, end up causing a bit of disarray/dysregulation beyond that specific cell population? Aha. This would explain why the immune dysregulation findings tend to be a bit patchy/inconsistent – if different patients have activation of different specific cell populations, then perhaps those different cell populations have negative feedback effects on different “other cells” – or perhaps there are too many variables involved for this to be meaningful.
Really interesting, thanks.
I really liked your explanation of this:
Is it possible that a person could have some antibodies to these receptors long before ME appears, causing either no or minimal/subclinical symptoms, as a kind of predisposing factor, and that a triggering infection could then cause the feedback system to go a little awry, leading to pathological antibody levels and a clinically obvious disease?
This makes a lot of sense to me:
So there is specific immune activation, which due to negative feedback on cells outside of that specific population, end up causing a bit of disarray/dysregulation beyond that specific cell population? Aha. This would explain why the immune dysregulation findings tend to be a bit patchy/inconsistent – if different patients have activation of different specific cell populations, then perhaps those different cell populations have negative feedback effects on different “other cells” – or perhaps there are too many variables involved for this to be meaningful.
Really interesting, thanks.
Maybe we're in the same subgroup! Time will tell.
It's a complex business, figuring out what distinguishes the responders from the non-responders. I like that Fluge and Mella are proceeding in a no-stone-unturned fashion.
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I find it so interesting this is the case!! I know for a fact I used to catch everything under the sun, and now I haven't had a proper cold or flu for over a year!! Would love to know the reasons or theories behind this occurrence!
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Hip
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The only hypothesis I heard was Rich Van Konynenburg's idea that interferon responses in ME/CFS might be ramped up and constantly activated, thus quickly killing any cold virus before it has a chance to take hold. I am not sure if there is any evidence to support this idea though.
I thought you read something about this, as you mentioned that you "came across information where it says that Rituximab might be helpful in treating a subset of CFS patients who have a chronically activated immune system."
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Found that information in the "Purpose" section of this current Rituximab trial study record detail: https://clinicaltrials.gov/ct2/show/NCT02229942