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

[Legendrew]

Yes, I tend to agree. But there may be subtleties. In RA there are HSP60 antibodies but I doubt they cause fatigue in RA - I think that comes from the specific antibodies - rheumatoid factor or anti-citrulline - and TNF release. HSP60 antibodies look to be a bit like the 'smoke with a fire' - an epiphenomenon maybe. As another example, in scleroderma you get more or less the same symptoms from one of three quite different autoantibodies. Everyone with scleroderma has an autoantibody but each person only has one of the three options. So, despite some sceptical remarks from some quarters, I am a believer in each autoimmune ME patient having their own specific autoantibodies (maybe twenty options?) as well as anti-HSP60 smoke. The difficulty with twenty different autoantibodies is that none of them might each show up in enough cases for anyone to take notice, so we may learn more from looking for the smoke at the moment. But I could be wrong.

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.

 

[aimossy]

nice to see @Legendrew still with us!.
@Jonathan Edwards I was wondering what you make of the new research published by Griffith Uni. You may be fully familiar with it allready.
It is in the latest research section.I can not remember the full title as I write this, I think it was something along the lines of the role of adaptive and innate immune system in chronic fatigue syndrome.
Any comments on it from people with knowledge in autoimmune diseases and immune system will be much appreciated.
It is pretty hefty reading and requires so much knowledge to make sense of with respect to what it means as in progress or more information on our immune systems.
Some of the tables in this study I found later were at the end of all the references.

 

[Kati]

@Jonathan Edwards I have a 'loaded' question for you.

Do you think ME is a rheumatologic diorder, and why or why not?
And in your opinion, what medical specialty would be best suited to see patients with ME

Thank you.

 

[MeSci]

nice to see @Legendrew still with us!.
@Jonathan Edwards I was wondering what you make of the new research published by Griffith Uni. You may be fully familiar with it allready.
It is in the latest research section.I can not remember the full title as I write this, I think it was something along the lines of the role of adaptive and innate immune system in chronic fatigue syndrome.
Any comments on it from people with knowledge in autoimmune diseases and immune system will be much appreciated.
It is pretty hefty reading and requires so much knowledge to make sense of with respect to what it means as in progress or more information on our immune systems.
Some of the tables in this study I found later were at the end of all the references.

I guess you mean this thread.

 

[aimossy]

Thanks @MeSci yes!

 

[Jill]

http://www.medpagetoday.com/Rheumat...=breaking-news&xid=NL_breakingnews_2014-01-14

Sanjay Gupta and others at Med Page review to trials and potentials of EBV. Very interesting.
Links EBV with RA

 

[MeSci]

http://www.medpagetoday.com/Rheumat...=breaking-news&xid=NL_breakingnews_2014-01-14

Sanjay Gupta and others at Med Page review to trials and potentials of EBV. Very interesting.
Links EBV with RA

Very interesting indeed, thanks.

 

[Firestormm]

http://www.medpagetoday.com/Rheumat...=breaking-news&xid=NL_breakingnews_2014-01-14

Sanjay Gupta and others at Med Page review to trials and potentials of EBV. Very interesting.
Links EBV with RA

Thanks Jill. You might think of posting as a separate thread and allow others to have a read. I am sure they will be interested. Or I can if you like

Edit: was reading the comments and there is one from Tom Hennessy which kind of freaked me out for a few seconds...

 

[Bob]

I've started a new thread for the article that Jill posted, because i think it's worth sharing widely.
http://forums.phoenixrising.me/inde...d-a-wily-virus-is-there-a-link-article.27989/

 

[lansbergen]

@ jonathan Edwards How would you classify the peritoneum and pleura B1 cells? Innate or adaptive system?

 

[Jonathan Edwards]

Re the Griffith study: For some reason I have not been getting flags for PR posts recently so I have not seen this until today. Thanks to those who picked it up. The results are complicated and I will need to go through the whole paper carefully. The markers for immature B cells are different from those used by others so there may be no direct comparison possible. Nevertheless, it will be important to see if there is a consistency here or not.

 

[Jonathan Edwards]

To catch up: Is ME rheumatological? I am afraid rheumatological just means something seen by a rheumatologist. Rheumatologists tend to reckon that pain in the arms legs or back is something they should at least be able to handle as a diagnostic issue so it would qualify for that reason. They tend to end up looking after problems most associated with joints but that is not exclusive. Muscle disease is often dealt with by rheumatologists, and also multisystem disorders of immune origin. So there isn't really a clear cut answer I fear!

 

[Jonathan Edwards]

@ jonathan Edwards How would you classify the peritoneum and pleura B1 cells? Innate or adaptive system?

B cells are adaptive. I am not sure that humans have peritoneal B1 cells. As far as I know this is a subset found in mice.

 

[Sasha]

To catch up: Is ME rheumatological? I am afraid rheumatological just means something seen by a rheumatologist. Rheumatologists tend to reckon that pain in the arms legs or back is something they should at least be able to handle as a diagnostic issue so it would qualify for that reason. They tend to end up looking after problems most associated with joints but that is not exclusive. Muscle disease is often dealt with by rheumatologists, and also multisystem disorders of immune origin. So there isn't really a clear cut answer I fear!

I had my first every rheumatology referral last week and was explaining the possible autoimmune connection in the light of the Norwegian findings and meeting with a blank look until I mentioned your name and the UK trial - you're very good PR for us in a consultation!

Are you able to update us on anything?

 

[aimossy]

@Jonathan Edwards alerts seem to stop if your watched threads gets full....at least that was the problem for me.
I had wondered whether you had seen the Griffiths paper or not. The people involved will be at the Invest in ME conference in the UK this year.

 

[Jonathan Edwards]

I had my first every rheumatology referral last week and was explaining the possible autoimmune connection in the light of the Norwegian findings and meeting with a blank look until I mentioned your name and the UK trial - you're very good PR for us in a consultation!

Are you able to update us on anything?

I don't really have any significant updates I am afraid, except to say that things are moving forward as fast as bureaucracy allows and I am very much looking forward to the IIME research meeting where I can meet all the researchers we have been discussing properly.

 

[Bob]

@Jonathan Edwards, if you are not receiving alerts for this thread (which has happened to me occasionally), you can easily fix it by clicking on 'unwatch thread' (top-right-hand-corner of the webpage, directly above the first post): After clicking on it once, it will now say 'watch thread', and if you click on it again then it will reset your alerts (for this thread only.)

 

[Mark]

Hi Jonathan. I'd be very interested in your thoughts on this paper re: an autoimmune basis for POTS:
http://forums.phoenixrising.me/index.php?threads/autoimmune-basis-for-pots.28723/

Potentially significant for ME/CFS?

 

[Jonathan Edwards]

Hi Jonathan. I'd be very interested in your thoughts on this paper re: an autoimmune basis for POTS:
http://forums.phoenixrising.me/index.php?threads/autoimmune-basis-for-pots.28723/

Potentially significant for ME/CFS?

This is quite a detailed study and the various components do seem to corroborate the idea that there may be antibodies binding to adrenergic receptors in these cases. My main worry is why they only apparently give an immunofluorescent result for one patient. If these were antibodies and they gave fluorescence of the sort indicated then it would seem obvious to screen the whole panel. I would also like to see more detailed images to confirm that the staining pattern was consistent with membrane receptors. It does look as if these patients have some sort of circulating factor that interferes with receptors but I would like to see it repeated by another group before I concluded that this was autoantibody.

If this finding can be confirmed I think it would add impetus to the search for autoantibodies in ME/CFS. The question would be what target receptor to set up your assays with to look for the antibodies.

 

[Bob]

Interesting Rituximab case report, in relation to EBV infection, posted by Ecoclimber:
http://forums.phoenixrising.me/inde...lt-successfully-treated-with-rituximab.29208/

Case Report
Epstein-Barr Virus Infection in an Elderly Nonimmunocompromised Adult Successfully Treated with Rituximab
Jacob P. Smeltzer, Matthew T. Howard, Wilson I. Gonsalves, and Thomas E. Witzig.
Case Reports in Hematology
Volume 2014 (2014), Article ID 641483, 4 pages
http://www.hindawi.com/journals/crihem/2014/641483/

Abstract
Epstein-Barr virus (EBV) is a ubiquitous virus that commonly affects children and adolescents. In addition to causing a viral illness, it is also associated with various malignancies in particular B cell lymphomas and lymphoproliferative disorders. Differentiating between the two processes can be a diagnostic challenge. Here, we present a case of an atypical EBV infection in an elderly patient with severe systemic symptoms, multiorgan involvement, lymphadenopathy, and negative EBV serology. Excisional lymph node biopsy demonstrated features of a lymphoproliferative process involving EBV. Despite supportive care, she experienced continued clinical deterioration and was successfully treated with rituximab. This case illustrates the diagnostic challenges of these cases particularly in the elderly who may have age related immunosenescence, the utility of EBV PCR testing, and the clinical efficacy of rituximab in clearing the infected cells.

I think it's a slightly different recovery time to that seen in ME patients in the Norwegian study:

Within two days of her first treatment, she had a dramatic clinical recovery. Her lymphadenopathy, confusion, headache, nausea, and fatigue all improved considerably.