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Hope for an ME/CFS Autoimmune Subset: A German Researcher Steps Forward

German Researcher Steps Up

Carmen Scheibenbogen MD is another sign that the ME/CFS field is slowly but surely hopefully catching on. Scheibenbogen is relatively new to this field, but she’s not new to medical research. A trained oncologist and hematologist as well as a physician and Professor of Immunology in Berlin, her research resume includes over 150 publications dating back 25 years.

scheibenbogen

Dr Scheibenbogen has identified what she believes is an autoimmune subset in ME/CFS. (Image from Invest in ME)

In short, she’s a respected and established researcher, and one from Germany to boot. (I can’t remember the last German researcher to take on ME/CFS.) Her path to ME/CFS has not been an easy one. Germany hardly acknowledges ME/CFS as a disease, and doesn’t fund ME/CFS research – if I’m reading her right, there is apparently literally no avenue to apply for ME/CFS research funding there.

Yet she’s very quickly become one of our most prolific researchers. Over the past four years her team has published no less than seven papers, has won two Ramsay Awards, and played a central role in the development of the new European Research collaboration, EUROMENE. Her biosketch lists CFS/ME, Immunodeficiency, and Cancer Immunology as her main research interests.

Scheibenbogen’s first ME/CFS publication In 2014 found ME/CFS patients mounting a feeble response to Epstein-Barr virus (EBV) . The reduced response to EBV reactivation could help explain the ups and downs seen, particularly during stressful situations.

In 2016, figuring that when Rituximab worked in ME/CFS it probably did so by whacking antibody producing B-cells, her group examined antibodies against a variety of receptors that affect blood flow, the autonomic nervous system, etc. They found that about 30% of ME/CFS patients in a large study (n=293) had increased levels of antibodies to adrenergic (B2) and/or muscarinic M3/M4 acetylcholine receptors (M3/M4).

That suggested that the immune systems of a significant subset of ME/CFS patients might be attacking the receptors on cells which regulate blood flow, lung functioning, muscle contractions and attention. Furthermore, the finding (a “remarkable” one they said) that the antibody levels of two receptors correlated with a host of immune factors (immunoglobulin levels, T cell activation, elevated ANA, TPO antibodies) suggested that this subset of ME/CFS patients are suffering from an autoimmune disease. Scheibenbogen has suggested that the kind of ME/CFS you have may be dependent on the kind of autoantibodies present in your system.

See Bad Bacteria, Brainstem Abnormalities and Progress with Rituximab: the Invest in ME Conference

Similar antibody findings have been found in a range of diseases (postural tachycardia, regional pain syndrome, Alzheimer’s, Sjogren’s syndrome, asthma) some of which have been associated with ME/CFS.

They also noted that immunoadsorption factors that are able to mop up these antibodies had proven to be helpful in some diseases. Two years later they put that idea to the test.

Possible Autoimmune Treatment

PLoS One. 2018 Mar 15;13(3):e0193672. doi: 10.1371/journal.pone.0193672. eCollection 2018.
Immunoadsorption to remove ß2 adrenergic receptor antibodies in Chronic Fatigue Syndrome CFS/ME.Scheibenbogen C1,2, Loebel M1, Freitag H1, Krueger A3, Bauer S1, Antelmann M1, Doehner W4, Scherbakov N4, Heidecke H5, Reinke P2,3, Volk HD1,2, Grabowski P1.

Adsorption

Adsorption vs absorption – By Daniele Pugliesi – File:Absorbimento e adsorbimento.svg, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=20486772

They used a blood purification technique called immunoadsorption to eliminate the B2 antibodies from people with ME/CFS who’d had a post-infectious onset and high B2 antibody levels. Immunoadsorption (IA) was given five times over seven days to completely wash out the antibodies. Over the next six months the participants’ symptoms, muscle strength, endothelial functioning and immune factors were watched.

Findings

Significant improvement eventually followed by a relapse was the order of the day. One patient who could barely walk prior to the treatment was able to walk several hundred yards at the end of the IA process. She completely recovered for seven weeks and then relapsed. Another patient improved enough to go back to work but then relapsed. Five patients who improved started to relapse by the end of the six months. Three patients – a good third of the study – felt significant improvements in fatigue lasting at least 12 months.

The levels of all four antibodies (B1, B2, M3 and M4) declined after the treatment in all 9 participants. These are good results which are hampered by the small sample size and lack of a placebo control. Through our experiences with Rituximab, Synergy and Mirogabalin we’ve learned how little to trust early results.  Still, research has to start somewhere and the results thus far present hope for a significant subset of ME/CFS patients.

Present and Future Work

Ramsay Award Standout

The Solve ME/CFS Initiative (SMCI) provides funding to five or so researchers every year in its Ramsay Awards. The Awards are quite competitive with SMCI receiving far more applications than it can fund, but over the past two years the Scheibenbogen group has won two – the only group to do so.

2016 Award

Citing “ample evidence of an autoimmune pathomechanism” the Scheibenbogen team will be digging into the genetics of their “autoimmune subset”. They’ll be determining if genetic abnormalities in the enzymes or transcription factor that turn on the autoimmune processes are present. They’re also analyzing the immune cells (dendritic cells, regulatory B-cells) known to produce autoimmune responses.

This is one of the first times that I’m aware of that a research group has targeted a subset and dug deeper into it.  Scheibenbogen’s focus is clearly good news for people in that subset but it’s also good news for people outside of it. If she’s found a robust subset then it needs to be peeled off from other ME/CFS patients because it’s undoubtedly confounding study results for those patients.

2017 Award

The 2017 Ramsay Award will determine if T-cells and monocytes are up to the task in ME/CFS. We know that NK and probably T-cells are laggards in ME/CFS patients’ immune systems, but other immune cells are largely untested.

Following on recent findings of impairments in energy production, the Scheibenbogen group is going to determine if T-cells and monocytes have the energy to spring into action when needed. Immune cells are mostly quiescent until they come across a pathogen, at which point they’re required to rev up their engines and explode into action. If they don’t have the energy to “explode” they’ll have difficulty fighting off bugs.

If I have it right, they’re also going to stimulate cells using adrenergic and acetylcholinergic factors to see if they affect their metabolism or energy production. Given the role these factors appear to play in the deranged stress response found in ME/CFS, finding a metabolic tie-in would be exciting indeed.

Simmaron Scheibenbogen Collaboration Underway

The Simmaron Research Foundation is also working with Dr. Scheibenbogen to identify the subset of Dr. Peterson’s patients who fit the autoimmune profile, and to further characterize the subset from a clinical perspective.

A Leader

Over the past five years Scheibenbogen has become deeply immersed in ME/CFS. She was the lead author of a paper on the EUROMENE network, which contains researchers and clinicians from 17 European countries. Euromene was accepted into the COST (Cooperation in Science and Technology) framework which was established by the European Union to support collaboration in scientific endeavors. While COST does not fund research studies, it does fund networks and provides networking possibilities across the European Union.

EUROMENE members

EUROMENE members

One goal of Euromene COST Action is to establish a “sustainable integrated network of researchers in Europe working in the field of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and to promote cooperation between research groups.

Coordination and collaboration appears to be becoming a bigger and bigger theme. The OMF and the SMCI held collaborative and networking meetings last year. The NIH research centers are collaborating on one large project. Canada’s May Montreal conference is focusing on establishing cooperative efforts to understand ME/CFS. (Dr. Scheibenbogen will be attending.) The OMF’s next conference is set for September of this year.

However Dr. Scheibenbogen got interested in ME/CFS, it’s great to see her get so involved so quickly. She reminds me of another relatively new researcher in the field – Dr. Maureen Hanson – who quickly cranked out research studies and is now leading an NIH ME/CFS research center. It’s good to see new researchers have success in this field.

Of course, the going is still tough. In an SMCI interview Dr. Scheibenbogen seemed astonished at the lack of opportunities for research into what she described as a frequent and severe disease.

But still the situation is very disappointing with so little support for patients and research and almost no interest from pharmaceutical companies to perform clinical studies. I am a trained oncologist and hematologist and there the situation is so different with so much research and drug development.

Like everyone else in this field, Dr. Scheibenbogen is a pioneer and pioneers by definition have rough going. Like the pioneers of old she’s forging a path through some hostile territory, not as the pioneers did in the old West but this time German medical circles.  Her work is getting results, though, results that her colleagues will surely notice.  Here’s to a new presence in the field who’s put, perhaps for the first time, Germany – the most powerful nation in Europe – on the ME/CFS map.

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25 Comments

  • Amanda Farthing

    April 1, 2018 at 6:59 pm - Reply

    hello I have been ill for 17 years after surgery giving birth I suffered extremely low body temperatures chronic fatigue chronic drugged up feeling suffer every day sleep problem

    can’t have normal life and desperate for my life back

    I believe this doctor would find information from Dr Masud haq who works in spire hospital Tunbridge wells Kent. he knows something about this illness.

  • Guang Rong

    April 1, 2018 at 7:29 pm - Reply

    The good news is there are new researchers and the bad news is they all have different guesses.

    • Cort Johnson

      April 1, 2018 at 8:52 pm - Reply

      Ha….You have a point – there are a bunch of guesses but a focus is emerging around the idea that some sort of possibly atypical autoimmune process is occurring in ME/CFS. Fluge and Mella, Scheibenbogen, Montoya and I’m sure others that I cannot remember at the moment believe that. I think its Light who believes that that autoimmune process may fit in with the metabolic problems that are being found.

      Hopefully at some point the immune, metabolic and ANS will start to come together. They are all there – it’s matter of piecing them together.

      • Brian Thompson

        April 2, 2018 at 2:57 am - Reply

        Hi Cort,
        Isn’t Mark Davis also looking into autoimmunity with his T Cell study?
        Also, when did that small trial described in the article take place? The one that used a blood purification technique called immunoadsorption to eliminate the B2 antibodies. Is there a follow up study or trial in the works for that so that they can test it on a larger population?

        • Cort Johnson

          April 2, 2018 at 6:09 pm - Reply

          Yes he is – thanks for the reminder. From a former blog on Mark Davis:

          “Either an autoimmune process or some sort of foreign antigen; i.e. an infection or toxin, had to be setting those T-cells in ME/CFS on edge. Davis’ findings are preliminary; he’s finding a strong signal, but needs to test more samples. If his findings hold up, the next step is attempting to identify what is tweaking the T-cells in the ME/CFS patients. If Davis can find that out, he may have a shot at discovering what is triggering the disease.

          Right now his bet is on an autoimmune process probably initiated by an infection. Everything he sees about the disease says autoimmunity to him right now.”

          …I just could not find a way to get in touch with Scheibenbogen so I don’t know about a larger trial. I hope this doesn’t turn out to be another promising small trial that doesn’t get followup.

          We are certainly going to learn more about this subset, though. She has funding to do more studies on them. The more study evidence the more chance of a trial.

          The patients all of whom had infection induced ME/CFS were identified between 2014 and 2016 so I’m guess the trial started somewhere between 2014 and 2017.

  • Me

    April 1, 2018 at 7:50 pm - Reply

    Thank you for researching!! postural is on the table for me right now, and several more tests in the next month. You can not imagine my surprise reading this today. Crossing my fingers 2018 will be the year of huge discoveries leading us to a better quality of life!!

  • Francis Martin

    April 1, 2018 at 9:00 pm - Reply

    Hi there is supposed to be a system of co-operation across health care systems in the European Union.
    The United Kingdom is currently in the European Union (Brexit).
    Is it possible to access the testing provided by this laboratory if you live in the United Kingdom [antibodies to adrenergic (B2) and/or muscarinic M3/M4 acetylcholine receptors (M3/M4)]? Is it possible to access this testing privately and if so how/at what cost?

    Detecting the autoantibodies referred to is difficult (comment from Jonathan Edwards). One possible way to improve this type of assay was highlighted by researchers at the Stanford Genome Technology Center [Google “Tweak to assay could bolster disease detection (Stanford Medicine News Center)”].

    Regarding ways to make this testing available in the United Kingdom. Try making a suggestion to the National Institute for Health and Care Excellence (NICE) i.e. that the test should be provided in the United Kingdom.

    In terms of making the test more reliable etc. Try making a suggestion to the European Commission (Horizon 2020 program etc). The European Commission funded 40 million euros/dollars of research into Lyme disease in 10 years; this included funding for the development of a test. The European Commission has not funded any ME/CFS research [European Commission’s response to parliamentary question “E-006901/2017”]. Possibly writing to your European Parliament representative (MEP) might help. For the USA try the NIH (Vicky Whittemore). Think Jennifer Brea – unrest.

    To summarise. This appears to be a very promising line of research. It would be useful for individual patients to have access to this testing and treatment. How do we achieve that?

  • Francis Martin

    April 1, 2018 at 9:09 pm - Reply

    This appears to be a very promising line of research. It would be useful for individual patients to have access to this testing and treatment. How do we achieve that?

    The United Kingdom is currently in the European Union (Brexit).
    There is supposed to be a system of co-operation across health care systems in the European Union.
    Is it possible to access the testing provided by this laboratory through the United Kingdom public healthcare system [i.e, testing for antibodies to adrenergic (B2) and/or muscarinic M3/M4 acetylcholine receptors (M3/M4)]? Is it possible to access this testing privately and if so how/at what cost?

    Detecting some/all of the autoantibodies referred to is difficult (comment from Jonathan Edwards). One possible way to improve this type of assay was highlighted by researchers at the Stanford Genome Technology Center [Google “Tweak to assay could bolster disease detection (Stanford Medicine News Center)”].
    In terms of making the test more reliable etc. Try making a suggestion to the European Commission (Horizon 2020 program etc). The European Commission funded 40 million euros/dollars of research into Lyme disease in 10 years; this included funding for the development of a test. The European Commission has not funded any ME/CFS research [European Commission’s response to parliamentary question “E-006901/2017”]. Possibly writing to your European Parliament representative (MEP) might help. For the USA try the NIH (Vicky Whittemore). Think Jennifer Brea – unrest.

    Good news story how do we deliver it?

    • Cort Johnson

      April 2, 2018 at 2:02 am - Reply

      Thanks Francis for lending your insights. I imagine that this kind of testing is not available to doctors. It does seem that strides are being taken rather rapidly in being able to improve the efficacy of antibody testing. Hopefully they will show up in ME/CFS studies.

      I didn’t know about the European Commission. Getting them involved must be a high priority of Euromene. The more people understand the truth of this illness and the limitations it cause the more they will be involved. Europe has been tainted by years of focus on behavioral research. I don’t mind behavioral therapies at all; the right ones can surely be helpful in reducing stress but they are not the answer for the vast majority of us. I think people are starting to get that.

  • Furio Picco

    April 2, 2018 at 2:28 am - Reply

    I would like to be more informed about ME research.

  • Karin

    April 2, 2018 at 10:28 am - Reply

    Very interesting, thanks Cort. I live in the UK and believe I’m in that ‘subset’ group. I tested positive for both ‘acetylcholine receptor antibodies and TOP antibodies’. I was tested 4 times for the acetylcholine receptors as the neurologist who originally tested me for it couldn’t understand why I didn’t exhibit features of Myasthenia Gravis (normally associated with these antibodies) and thought perhaps a mistake had been made. It hadn’t as sure enough all 4 tests were positive.

    I believe as Francis Martin points out, there must surely be a way to achieve across the board testing for these antibodies for those with ME/CFS and subsequently combine the results.

    Does anyone know if Scheibenbogen or Dr. Peterson are taking on patients who belong to this subset ? I’d be more than happy to join a trial.

    • Cort Johnson

      April 2, 2018 at 6:06 pm - Reply

      So you fell through the cracks – a typical ME/CFS patient! We just don’t fit into any of there pictures. I’m glad these tests are available.

      I don’t know but if you can get to them it would be great to get into a trial. I don’t have Scheibenbogen’s email address – I was going to try and found out about a larger trial. (I also wanted to know how she got involved…)

      • Karin

        April 3, 2018 at 10:59 am - Reply

        Yes indeed Cort, I would very much like to take part in ‘any’ trial of this subset as the results of my tests point to likelihood I’m in that group. With the “Simmaron Scheibenbogen Collaboration Underway” is it possible I could gain an email address of Dr. Scheibenbogen through this collaboration ? I have googled every which way and cannot find a way to contact her. How does one put themselves forward if they are one of this subset for a trial? Frustrating.

    • Kurt

      April 2, 2018 at 10:19 pm - Reply

      @Karin, Glad you mentioned Mysethenia Gravis, that was my thought as I read this article. There are some interesting parallels between MG and ME/CFS.

      I am curious what your Neurologist concluded? Did you get any diagnosis, or a general statement about having an unknown autoimmune condition? Anything useful?

  • Francis Martin

    April 2, 2018 at 12:27 pm - Reply

    Cort, thank you for your reply.

    Here’s Jonathan Edwards comment regarding the difficulty in testing for muscarinic ACh receptor antibodies:
    “The only caveat to flag up is that muscarinic ACh receptor antibodies have a reputation for being a bit of a pain in terms of reproducibility—” [http://forums.phoenixrising.me/index.php?threads/antibodies-to-%C3%9F-adrenergic-and-muscarinic-cholinergic-receptors-in-patients-with-cfs.40109/page-3].
    Jonathan was commenting on Carmen’s 2016 paper titled “Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome”.

    I’ve only looked briefly at your article/the paper but it appears that these autoimmune antibodies may be causing the illness in some people. Once you know that autoimmune antibodies are causing an illness then a whole range of treatments may be available. E.g. NMDA receptor antibody encephalitis appears to be managed by off the shelf immunosuppressants. This emphasises the importance of the diagnostic test for these autoantibodies (muscarinic etc). MS, an autoimmune disease, also appears to be treated by wiping your immune system and rebooting with stem cells; not something you’d try unless you were sure you had the autoimmune form.

    Your article will be read in many countries which are members of the European Union. The European Union has developed similar tests for Lyme disease etc [Horizon 2020]. I think we (patient community/families) need to think about whether we can encourage the European Union to fund the development of a diagnostic test for these autoantibodies (muscarinic etc).

    I agree with your comments re the psychological approach. Ron Davis said some similar things in one of his videos. To partly plagiarise someone; I think the psychological approach will mean that if you’re currently housebound you still will be but you may be able to (better) deal with the psychological impact. Carmen’s study took someone who was housebound and helped them to walk hundreds of metres.

  • Caroline Christian

    April 3, 2018 at 1:11 am - Reply

    You can access this testing through a private lab in Germany called CellTrend. Costs about 500 Euro to get a panel of 8 autoantibodies done, including the autoantibodies against the adrenergic and muscarinic receptors. These tests were developed in conjunction with Dr. Scheibenbogen.

    Beta-1 adrenergic receptor auto-antibodies
    Beta-2 adrenergic receptor auto-antibodies
    Muscarinic cholinergic (M1) receptor auto-antibodies
    Muscarinic cholinergic (M2) receptor auto-antibodies
    Muscarinic cholinergic (M3) receptor auto-antibodies
    Muscarinic cholinergic (M4) receptor auto-antibodies
    Muscarinic cholinergic (M5) receptor auto-antibodies
    Alpha-1 adrenergic receptor auto-antibodies
    Alpha-2 adrenergic receptor auto-antibodies

    • Lynne

      April 11, 2018 at 12:31 am - Reply

      Caroline – have you been tested? Thanks for that info – I may look into it myself. I had the FM/A test done which my health care would not pay for, cost of $900. The goal of having the test is there’s expected to be a trial in Boston involving a vaccine. In order to have access to the eventual study, having a positive FM/A test is the gateway. Thanks again for that info.

      • Andrea

        July 23, 2018 at 10:16 pm - Reply

        Hi Lynne,
        Do you have any information about the trial in Boston that you mentioned, or know how I can find out about it?
        Thanks.

  • Petra

    April 3, 2018 at 10:41 pm - Reply

    What is confusing me about this theory is how these autoantibodies cause hypometabolism -PDH dysfunction?
    I have very high CellTrend antibodies, so this is missing puzzle for me to believe they’re very significant in my illness.

    BTW, Alzheimer was mentioned, if anything that’s the disease I relate most to (in less extreme form, but I am young). Can you share research where they found any of these antibodies in Alzheimer? I didnt run into that.

    • Cort Johnson

      April 5, 2018 at 8:25 pm - Reply

      I don’t know about Alzheimer’s but similar antibodies have been found in POTS.

  • Linda Julian

    April 4, 2018 at 4:23 pm - Reply

    Blood purification technique is brought up. My question for several weeks has been, blood irradiation. I have seen this work and help people with undefined medical issues, who have been run through the USA traditional medical mill. It’s effects are short term and require repetition. It was commonly used with dedicated clinics pre-penicillin. It is now used in homeopathy. It is comparatively cheap. In essence turning your own blood into a type of treatment for what ails you.
    I am intent on finding a homeopath to try this myself.

    • Cort Johnson

      April 5, 2018 at 8:21 pm - Reply

      Thanks for passing that on and good luck!

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