Invest in ME/Prof Jonathan Edwards statement on UK Rituximab trial, 30 July

[aimossy]

@Marco Thanks for the above, that is really interesting. I did find some papers about some conditions with low ADMA and have no clue where I found those in now. I came away after flicking through these feeling that quite a few illnesses may have low ADMA, so I thought well it may not be unique to ME but still abnormal in some illnesses. I wonder if its one of those things where if your body is under strain it shows up ( yes rudimentary thinking, I'm not proclaiming some scientific brain).

 

[Marco]

@Marco Thanks for the above, that is really interesting. I did find some papers about some conditions with low ADMA and have no clue where I found those in now. I came away after flicking through these feeling that quite a few illnesses may have low ADMA, so I thought well it may not be unique to ME but still abnormal in some illnesses. I wonder if its one of those things where if your body is under strain it shows up ( yes rudimentary thinking, I'm not proclaiming some scientific brain).

Interesting. The only other one I found was sickle cell disease. You may be right about low or high this or that being a compensatory reaction to the underlying illlness rather than contributing to it?

 

[aimossy]

Well, yeah exactly! That is what I was wondering
Still if it is "significantly low" and the stats are good and across the board in short duration patients with decent cohort, you would think this is significant?
Like you say, seems involved with various pathologies. I was thoroughly interested how low levels could possibly effect NO after googling it.

 

[Leopardtail]

I'm sorry if this is dragging up an old point, I've only recently been going through this thread for the comments I have missed. The concept of 20+ autoantibodies being present within the entire potentially autoimmune based ME cohort is something that sounds very interesting and is something I doubt many people have ever considered.

From my reading around the subject it seems clear that there is a definite 'neurological' dysfunction in ME patients and the most common term I see when reading articles around this subject are autonomic dysfunction (which, while an interesting topic is something of an overly broad term) and HPA axis dysfunction (hypothalamic-pituitary-adrenal axis). I admit that much of the discussion regarding this is somewhat beyond me (although I intend to read up on the subject at some point) however it seems an interesting concept, especially given that there could be thousands of unique targets within the hypothalamus and pituitary gland. I'll be interested to see whether the study investigating possible hypothalamus targeted antibodies comes up with anything.

Such dysfunction could go some way to explain the vast array of symptoms patients experience and also the seemingly vast spectrum of morbidity between patients, with some completely bed bound while others are able to struggle on, working full-time. It could also explain why generic test such as blood counts, ESR and CRP are very often normal in patients despite high levels of disability.

That aside, I do have a query regarding the rituximab trial. Are you also recording patients self reported symptoms alongside results from the pre-trial study? It would be interesting to see whether certain symptoms such as swollen lymph nodes, headaches, tremors etc are more or less frequent in a possible responding group - although I doubt this will prove a significant difference I would expect some symptoms to appear more frequently in those who respond. Acute/gradual onset could also have a huge difference although i'm certain these are things you've already considered. I was reading a paper recently exploring how cytokine fluctuations in Lupus appear to correlate to differing symptom complexes (http://www.ncbi.nlm.nih.gov/pubmed/8445045). It's interesting to see the variation that exists even within a fairly well defined disease such as lupus. If ME did truly have numerous different causative autoantibodies perhaps the degree of variation within ME would be even greater.

Leg,

this is a weird one, most chronic diseases elevate ESR and diagnostically that is all medics look for. There is however opinion that in ME we have low ESR and that is highly exceptional.

Just thought that might interest both you and prof edwards.

Leo

 

[Leopardtail]

Professor Edwards,

I have seen claims in the past that low melatonin can be associated with allergy, and high melatonin with auto-immunity. Do you have any opinion on this?

 

[Sasha]

Not sure if an epigenetics study by McGowan has been discussed here - it's on Cort's blog today, who says (among other things):

High rates of epigenetically altered immune regulating genes suggested ME/CFS patient’s immune systems are skewed to a Th2 immune response. Altered methylation rates in the genes involved in regulating the adaptive immune response (T and B cells) could help explain the inflammation present in ME/CFS. The authors highlighted a few genes that had been epigenetically altered. One hypermethylated gene (BCL10) in the ME/CFS patients activates a transcription factor called NF-kB that’s responsible for triggering a wide inflammatory response. Maes has proposed that the NF-kB inflammatory pathway is enhanced in both ME/CFS and depression. Another epigenetically altered gene in ME/CFS is associated with EBV infection of B-cells.

Read more: Epigenetics Study Highlights Immune Issues in Chronic Fatigue Syndrome http://www.cortjohnson.org/blog/201...ights-immune-issues-chronic-fatigue-syndrome/​

There's a webinar today by McGowan on ME/CFS and epigenetics, linked to from Cort's blog.

 

[Jonathan Edwards]

Not sure if an epigenetics study by McGowan has been discussed here - it's on Cort's blog today, who says (among other things):

High rates of epigenetically altered immune regulating genes suggested ME/CFS patient’s immune systems are skewed to a Th2 immune response. Altered methylation rates in the genes involved in regulating the adaptive immune response (T and B cells) could help explain the inflammation present in ME/CFS. The authors highlighted a few genes that had been epigenetically altered. One hypermethylated gene (BCL10) in the ME/CFS patients activates a transcription factor called NF-kB that’s responsible for triggering a wide inflammatory response. Maes has proposed that the NF-kB inflammatory pathway is enhanced in both ME/CFS and depression. Another epigenetically altered gene in ME/CFS is associated with EBV infection of B-cells.

Read more: Epigenetics Study Highlights Immune Issues in Chronic Fatigue Syndrome http://www.cortjohnson.org/blog/201...ights-immune-issues-chronic-fatigue-syndrome/​

There's a webinar today by McGowan on ME/CFS and epigenetics, linked to from Cort's blog.

We flagged up this paper in one thread earlier in the week (I forget which). It is interesting to me because it picks out two genes relevant to B cell maturation BCL10 and CD23. The UCL lab has already homed in on CD23 as an interesting molecule for ME studies. If that means we are on to a real biological effect that would be tremendous, but it might just be coincidence. Its exciting but we need to be careful.

I have a few comments about the commentary. I personally do not interpret things in terms of TH1/TH2. To me these are artificial categories derived from mouse experiments. In the human I think we have to consider each pathway and cytokine on its own merits. BCL10 links in to nF-kB but then so does almost everything and I doubt this has much to do with inflammation - which is OK since I don't think there is much inflammation in MEs. I would also make the point that epigenetics is a new word but it doesn't mean anything different from what we used to call 'differentiation' or 'maturation' - i.e. a rather long term commitment to a particular pattern of gene expression. It is not a 'new causal factor in disease', it is part of the downstream mechanisms we have been aware of for a long time. The methylation mechanism has been known since 1980 at least but has only recently been reasonably easy to measure in bulk. Exactly how methylation is retained in dividing clones is I think still uncertain - that was the bit that was always a bit mysterious.

 

[NK17]

This is more than interesting guys!
I actually smell something big here.
EBV infected B cells, hyper and hypo methylated genes! This fits perfectly for some of us. My ME started back in 1981, my annus horribilis, when I came down with a glorious case of Infectious Mono. Keep on digging guys

 

[catly]

This is more than interesting guys!
I actually smell something big here.
EBV infected B cells, hyper and hypo methylated genes! This fits perfectly for some of us. My ME started back in 1981, my annus horribilis, when I came down with a glorious case of Infectious Mono. Keep on digging guys

Webinar with McGowan is being held now for those who are interested. They'll probably have it posted up on the SolveCFS Initiative website in a couple of weeks for those who missed it.

 

[catly]

I don't mean to highjack this thread, but just wanted to say that I listened to the webinar I noted above and honestly I wasnt' that impressed. I'm not sure how valid the whole field of "epigentics" is in terms of advancing medical science. Of course all of this is way over my head but when anyone starts talking about meditation and diet as an intervention for MECFS they start to loose credibility with me.

For anyone who is interested they said the webinar should be posted in a few days on their youtube channel.

I do think the field of genomics in MECFS and all of medical science is very exciting and worth investing in. In this area, I would give my support to Ronald Davis at Stanford http://cfsresearchcenter.org/.

 

[NK17]

I don't mean to highjack this thread, but just wanted to say that I listened to the webinar I noted above and honestly I wasnt' that impressed. I'm not sure how valid the whole field of "epigentics" is in terms of advancing medical science. Of course all of this is way over my head but when anyone starts talking about meditation and diet as an intervention for MECFS they start to loose credibility with me.

For anyone who is interested they said the webinar should be posted in a few days on their youtube channel.

I do think the field of genomics in MECFS and all of medical science is very exciting and worth investing in. In this area, I would give my support to Ronald Davis at Stanford http://cfsresearchcenter.org/.

I could not listen to this webinar, I will catch up when it will be uploaded on Youtube.
I completely agree with you @catly on recoiling when I hear lifestyle's tips mentioned in conjunction with ME/CFS! Meditation, really?! I meditate consciously and unconsciously, every single day, just to survive this nightmare I've been living with for so many years I've lost counts!

I also wholeheartedly second @catly support to Dr. Ronald Davis research center at Stanford. PWME can't ask for a better ally, a brighter mind, a greater scientist, a more amazing human being.
I think he is our dark horse and he will bring us out of the tunnel.

 

[lansbergen]

which is OK since I don't think there is much inflammation in MEs.

I disagree. There is much imflamation during flare ups. It just manifest different. Not all classic sighns show.

 

[Valentijn]

I disagree. There is much imflamation during flare ups. It just manifest different. Not all classic sighns show.

Agreed ... my ESR has been consistently high since becoming ill, and sometimes CRP as well. Every urine sample taken over the past three years has had traces of blood, of which mild inflammation is a common cause. And I'd imagine there's a lot of inflammation involved when I eat the wrong foods and swell up for about 24 hours afterward Oh, and the chronic ME headache seems likely a result of inflammation, since fish oil keeps it away for some of us.

 

[Jonathan Edwards]

I don't mean to highjack this thread, but just wanted to say that I listened to the webinar I noted above and honestly I wasnt' that impressed. I'm not sure how valid the whole field of "epigentics" is in terms of advancing medical science. Of course all of this is way over my head but when anyone starts talking about meditation and diet as an intervention for MECFS they start to loose credibility with me.

For anyone who is interested they said the webinar should be posted in a few days on their youtube channel.

I do think the field of genomics in MECFS and all of medical science is very exciting and worth investing in. In this area, I would give my support to Ronald Davis at Stanford http://cfsresearchcenter.org/.

Hijacking welcome to my mind. Interesting to hear your take. I had to miss the webinar but it would be good if someone flags up if it gets on the YouTube site. I agree that epigenetics is a distraction buzzword. But the result they came out with might be important. Mixing that with meditation and diet does sound a bit worrying!

 

[MeSci]

Agreed ... my ESR has been consistently high since becoming ill, and sometimes CRP as well. Every urine sample taken over the past three years has had traces of blood, of which mild inflammation is a common cause. And I'd imagine there's a lot of inflammation involved when I eat the wrong foods and swell up for about 24 hours afterward Oh, and the chronic ME headache seems likely a result of inflammation, since fish oil keeps it away for some of us.

I think that my ESR/CRP have (almost?) always tested normal. Subgroups again...?

 

[MeSci]

Hijacking welcome to my mind. Interesting to hear your take. I had to miss the webinar but it would be good if someone flags up if it gets on the YouTube site. I agree that epigenetics is a distraction buzzword. But the result they came out with might be important. Mixing that with meditation and diet does sound a bit worrying!

I agree re the meditation. However, diet fits into microbiome and immune research. Diet modifies the gut microbiome, which I consider a likely reason why some see so much benefit from it. The gut microbiome affects the immune system - indeed it is crucial to the development of a functioning immune system. I posted an article from Scientific American on this topic here.

 

[Marco]

Just flagging up a sceptical view of some microbiome research :

Microbiology: Microbiome science needs a healthy dose of scepticism

http://www.nature.com/news/microbio...of-scepticism-1.15730?WT.mc_id=TWT_NatureNews

 

[MeSci]

Just flagging up a sceptical view of some microbiome research :

Microbiology: Microbiome science needs a healthy dose of scepticism

http://www.nature.com/news/microbio...of-scepticism-1.15730?WT.mc_id=TWT_NatureNews

I skim-read it incompletely and didn't really get the main points as not time or brain function to absorb it properly. But I like some of the comments, especially:

Yes, its true that microbiome science needs a healthy dose of scepticism. Just like every other branch of science, lets not lose sight of that.

which sums up my own view!

 

[Gijs]

Dear professor Edwards, can it be that EBV is messing up the B-cels to a different state? Or is this to simple.

 

[catly]

Webinar is posted. Interested in hearing others opinions. I think I will start a separate thread on this.