RME Conferences in Stockholm and Malmö, October 2017.

[Jo Best]

Two meetings hosted by the Swedish National Society for ME Patients, RME, in October 2017.
Full details here: http://rme.nu/konferens

Dates:

Wednesday 18th October in Stockholm

Thursday 19th October in Malmö

Topic:

'Exhaustion even on cellular level. Cardinal symptoms, biomarkers and possible treatment'.

Speakers:

Jonas Blomberg, Uppsala.

Maureen Hanson, Cornell.

Geraldine (Jo) Cambridge, UCL.

Per Julin, MD, Stora Sköndal Neurorehabilitation

RME is a member of the European ME Alliance: http://www.euro-me.org/news-Q22017-004.htm

​

 

[Helen]

Titles of the talks in English, as it might be difficult for most to navigate on a site in Swedish:

Anomalous microbiome and metabolic profiling in ME/CFS-patients
Prof Maureen Hanson, Cornell University, USA

ME/CFS and the immune system. Where are we now?
Geraldine (Jo) Cambridge, PhD, Dep. Medicine, University College, London

Biomarkers for ME /CFS in the cerebrospinal fluid
Prof. Jonas Bergquist, Inst. f kemi, Uppsala Universitet

Neuroradiological studies in ME/CFS
Dr Per Julin, MD, ME/CFS-mottagningen, Stora Sköndals Neurorehabilitering, Stockholm


The talks during these annual seminars use to be video-recorded and posted about on PR. Though, I believe that only the first and second one will be in English.

 

[Jo Best]

Thank you @Helen.

 

[Helen]

The conference in Malmö tomorrow will be LIVE-streamed here from 1 p.m.

Maureen Hanson and Joe Cambridge will be the second and third speaker to give their talks, according to the program here

The talks will probybly be video-recorded and published later, but this is for you who can´t wait to hear them .

 

[Helen]

The conference in Malmö tomorrow will be LIVE-streamed here from 1 p.m.

Sorry, the LIVE-streamed conference in Malmö will be on Thursday, 19th.

@Jo Best , @BurnA , @Scarecrow , @Joh

 

[Hajnalka]

I fell ill while living and studying abroad in Uppsala (and this dream turned into a nightmare) - so I feel a strange interest/connection to Sweden and ME.

 

[Helen]

@Joh , sorry for that. Both that you actually fell ill (wherever it happened), and that it was in a quite nice city (or is it a town in your view?). It must have been really hard to be sick as a foreign student, both young and away from home.

I do hope that you´ll recover and will be able to go back and fully enjoy Uppsala and Sweden .

 

[Jo Best]

Live now - http://rme.nu/malmo-2017-live-stream

 

[Demepivo]

I was impressed by Jonas Berquist when he spoke at the recent Stanford Symposium. Explained his work with enthusiasm & clarity

 

[ukxmrv]

Maureen Hanson talking in English now.

Starting with the SF36 questionnaire. ME/CFS patients causes more impact than congestive heart failure and MS

Then outbreaks with a slide of a list. She is hoping that physicians will report and investigate outbreaks using modern technology.
Lyndonville (sp?) people displayed subtypes years after the outbreak (i.e some had more pain) but she thinks same pathogen.

Talking about some biological differences that cannot be explained by psych

Gut microbiome - can be affected by diet, healthy or sick, genotype. age

ME being investigated because patients complain of gut symptoms

Need to characterise ME gut vs healthy individuals

Leaky gut allows pathogen to slip in between cells and get into bloodstream and this creates inflammation

Studied patients of one particular ME doctor (maybe Leveine?). ME patients had 3 higher proteins LBP, LPS, and something else.

Fatty liver disease, Crohns, HIV/AIDS disease and a few others have the same finding

Lower diversity of species in ME samples. Controls had more species. Loss of species richness. 24 genera were either greater or lower in ME/CFS. They were all known to be beneficial and were higher in controls. Produce Buterate.

In conclusion - less diversity, less anti-iinflammatory bacteria

83% accuracy rate to determine if one has ME/CFS from these samples

They have started looking at the viral-like composition in the gut called Bacteriaphages. These play a role in Crohns and ulcerative colitis.

They haven't done enough to detect human viruses in the gut as yet.

What attempts to alter microbiome - diet, prebiotics, probiotics, (can't grow most of the bacteria that are in our gut to make probiotcis), anti-biotics (both good and bad results), fecal transplant.

People can get worse with pre or pro biotics. Can do harm.

Norway study - new which will be coming up. They will be looking at 74 ME patients who will get fecal transplants. Do tests before and after. CD14 and LBP will be studied

 

[Murph]

Hanson talking about the gut.

 

[ukxmrv]

Now on to PEM (Maureen Hanson)

Talking about how PEM is described in the IOM report

For some people lying in bed and getting out of bed causes PEM and others getting out of the house to a doctors appointments

One way to induce PEM is to use a Cardio-pulmonary test over 2 days. Talking about Snell et al paper

How do we know these results are valid or not faked by patients not doing their best effort.? No way anyway can deliberately alter the amount of (and then talks bout a couple of tests - sorry didn't get a note of them)

Collaborating with Betsy Kellar. Finds sedentary controls. Compares to ME/CFS patients. If she puts a control on an exercise bike and the Vo2 max increases. Respiratory exchange rate, BP, HR goes up. 2nd day Vo2 max is similar. Max HR and BP slightly lower.

A ME/CFS patient on the same test. Vo2 max is better than controls on day 1 but not on day 2. Their Aerobic Threshold is also lower on day 2.

One patient's BP didn't go up during exercise. There are different types of dysfunction in the ME patients - not all the same.

Has tested 94 patients and 39% had an aerobic dysfunction, 30 something % an autonomic dysfunction, 33% reproduced normally. Younger patients and not sick as long reproduced more normally

 

[ukxmrv]

- Metabolites now (Maureen Hanson)

Different results due to different testing methods

Nothing new to report

- talking about new studies and her labs

study 1 - Oxydative stress using brain scans (MRI and PET) before and after exercise test. Looking for neuro-inflammation and antioxydants

study 2 - metabolites in plasma before and after exercise test. Extracellular vesticles (sp?). She wants to see if these are implicated in PEM

study 3 - RNA / gene expression. Particular type of white blood cell in ME/CFS. Get the RNA out of individual cells and find out if there is a particular cell. Single cell sequencing

Biomarkers - don't need to be specific to ME for treatment. Doesn't matter if the same as in Parkinson's disease. Do they normalise under a drug treatment. Could reveal identity of existing drugs that could be used to improve patients.

- Questions now

1. Why no outbreaks since 1990 ?

The pathogenic virus could be weaker OR these viruses are now out in the general population and it's now sporadic and there is some immunity, OR our health system could be better now

Interesting that outbreaks tracked with HIV/AIDS she says

COFFEE BREAK now and then back with Jo Cambridge "ME and the immune system"

 

[Murph]

Hanson's slide on the Keller CPET tests. 70% of patients who meet criteria fail to reproduce their day 1 performance on day 2.

Some have blood pressure problems, she said. Others test normal - these are mostly young people who have not been ill for very long.

 

[Murph]

There was one new thing in Hanson's talk I think. Her as yet unpublished Study of the gut virome found more bacteriophages (viruses that attack bacteria) than in controls. A similar effect has been seen in chrons and colitis. She hypothesised that the phages could be killing off gut bacteria contributing to the well documented lack of diversity and dysbiosis.

I've always thought there needs to be somethign upstream of simply hvaing the wrong bacteria in your guts. Why is it so hard to change them? After all, even if FMT works it seems to reverse after a while. A chronic oversupply of bacteriophages could be locking in dysbiosis.

 

[A.B.]

What does physiologic dysfunction refer to?

 

[Jo Best]

Continuing at a diffent youtube link -

 

[ukxmrv]

Jo Cambridge - Uni College London

Prof of Immunology. Works with Jonathan Edwards

Co-operates with Norwegian team

What B cells are doing in ME/CFS. Results of Norway. Big results should be out in next few weeks

How to possibly identify patients who could benefit from Rituximab treatment?

ME is being recognized as a physical disease now, people in my department in the UK will not agree with me but at least we are here

Virtually ever patient we have studied relates to a viral or inoculation onset

Signalling pathway in stress

Need something that perpetuates the chronic disease. Need something that is hard wired and keeps come back.

3 steps
Any kind of insult will cause a damage / danger signal
When the infection takes hold the immune system steps in
Memory immune response - B cells make antibodies

Innate immune system - killing of virus infected cells - NK cells - initial response in ME/CFS could be where things start to go wrong

NK cells results published in ME - could be antibody or soluble factors

Cytokines profiles - can tell you what the stimulus is and what the effects will be in lots of tissues

In ME/CFS different cohorts - some cytokines up and down. Decent control cohorts - look at PWME after EBV. Disease duration. Adolescent patients

B cells - inconsistent data. Some say more /less etc.

What did strike us when we reviewed the data was the B-cell viruses were involved in onset for many patients. Onset of B-cell Lymphoma.

Some of the Cytokines reported raised in ME/CFS are related to B-cells

Rituximab used for 20 years in RA and 10 years in Lymphoma. Brave Norwegians she calls them. Rituximab used in 8/10 different diseases in her unit?

Ethical approval could be hard to get as it is a IV infusion - has been said to her. In her own patients not much in the way of problems with reactions. They currently do a test to see if B cells are killed.

Peripheral B cells come out of bone marrow. New naive B cells, most die but some are selected and turn into memory cells or plasma cells. Rituximab doesn't kill stem cells and pro-B cells. Rituximab using immune system to kill B cells. They coat cells and the macrophages kills them.

In tissues B cells are resistant to being killed.

Rituximab is given in large quantities 1-2 grams and coats the B cells in the bone marrow and stops them coming out plus kills the peripheral cells.

Summary of data so far (running through existing research)

£2000 pounds a go for Rituximab in the UK. The blood levels of Rituximab in the Norway studies was huge. She thinks they used a lot of the drug.

She talks about RA in the UK - there are seropositive and seronegative patients. They only use seropositive patients. Showed a slide of all the different condition they treat and the antibody tested

IResponse to Ritaximab epends on how quickly the autoantibody cells regenrate - precusors of autoantibdies

A lot of patients are being treated off label and they haven't responded but it takes a while. She thinks it is a soluble factor or something subtle rather than just the B cells themselves.

Maybe stopping the B cells interacting with other immune cells that could be happening.

If Rituximab works we need to look at B cells.

When the B cells comes back they come back from the naive and the interesting things is that when they B cells relapse is it bad B cells or the number? It's the quality and not the number

Graph of patient in Norway - during period of getting better there were no B cells in the blood. When B cells removed get rid of all the ones turning into memory cells. When they come back (maturing) the ME symptoms came back.

This helps them to work out how to give a dose to stop patients relapsing

Some B cells trigger a relaspe when they come back but some Norway patients are still fine. That suggests that the B cells need to do soemthing to activate again.

Metabolism - B cells sensitive to metabolic activity. How they interact with other cells / pro-inflammatory etc. T cells boring.

B cells can maybe give us indication of what could be happening in our cells. 2 years ago with Fane looked at extended phenotype analysis. 20/30 patients.

No differences in subsets with controls. Then looked at something else - major differences. Subtle. Overlapping populations of B cells. CD24 higher in ME B cells and more molecules per cell. Importnat molecule in B cell maturation. 2 difference in EBV response. AMPK is a key producer. ATP levels. This is related to CD24 and they don't know if the pathway is functioning in ME patients.

Talks about IGM antibodies to EBV

EBV response may be disturbed

B cells have different energy requirements depending on stimulus.

Graph on products between T and non-T dependent responses - lactic acid higher on one

Question - do any of these ME patients have IGM rheumatoid factor or CCP antibodies ?

Answer - in Norway a few IGM but low titres and UK no CCP antibodies

 

[Jo Best]

Many thanks @ukxmrv and @Murph.

 

[Jo Best]

What does physiologic dysfunction refer to?

I'm not sure but this extract is from the 'Physiology research' page on the center website:

Maureen Hanson’s group is currently seeking funding to measure changes in gene expression, signaling molecules, and metabolites in patients at baseline and following induction of post-exertional malaise through CPET testing. The Hanson group has already collaborated with Dr. Keller to measure physiological and molecular responses to exercise by a healthy twin and his identical twin who has ME/CFS.
http://neuroimmune.cornell.edu/research/physiology/