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The easiest breakthough possible: MBL deficiency and CFS

Discussion in 'Action Alerts and Advocacy' started by Leitwolf, Aug 7, 2011.

  1. Leitwolf

    Leitwolf

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    I could get nuts over it, because it is so obvious. Still, nothing is moving.

    MBL deficiency is the most common immune defect. I do know, from various boards, that its prevalence among CFS patients is high above the average. Of course, most of them have never been tested for it

    A simple blood test for MBL costs around 30 Euros (might be somewhat more expensive in the U.S.). Running the test on a sample of 100 patients would thus cost a few thousand dollars / euros.

    What is to be gained? If there is an correlation between the two (and I have little doubts there is), there would be a crystal clear physiological cause for CFS. For a large group of CFS patients there would also be a ready treatment, or should I rather say cure available. Human MBL can both be gained from plasma as well as a recombinant product.

    What's more: MBL is known to be a relevant contributing factor in chronic herpes infections:
    http://www.biochemsoctrans.cn/bst/031/0768/0310768.pdf

    Up to the present day however, it seems there has not even made an attempt to link the most frequent immune defect to a disease with 17 mio sufferers world wide. This is ridicolous! There must be a patient organization or a specialist willing and able to run this simple research.
    merylg and alex3619 like this.
  2. eric_s

    eric_s Senior Member

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    I will check it out and if the test is available, it might be relatively easy to have a significant number of people doing it. Of course that would not be in the context of a study, but it would still be data.

    Btw. can you tell me something about the situation in Austria? As far as i know there is no Austrian group anymore, right? I think there used to be one, but it doesn't exist anymore.
  3. eric_s

    eric_s Senior Member

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    Can you post links to labs that offer the test? And papers or articles linking it with ME/CFS? That would save me some time and energy. Thanks.
  4. mellster

    mellster Marco

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    Wow - very interesting. A quick glance does not suggest tests ready in the US that can be ordered online and standard labs do not seem to have it either. It is interesting that this seems to be a genetic defect as it would explain why it often runs in the family. Is there any supplement that can enhance the MBL pathway or provide MBL directly even slightly except for plasma infusions?
  5. mellster

    mellster Marco

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  6. Leitwolf

    Leitwolf

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    This table gives you an idea on how frequent deficiencies are:

    http://diabetes.diabetesjournals.org/content/53/6/1570/T2.expansion

    My MBL level is <10ng/ml
    I found another user "Jenny" stating her level might be about just as low:
    http://forums.phoenixrising.me/show...-Fatigue-clinic-London/page4&highlight=lectin
    (sorry, but the search function on this board is miserable)

    These ultra-low levels are quite rare among healthy ppl but seem pretty common in CFS patients.

    I did a simple inquiry on a german board:
    User / MBL
    Sonnenblume1703 / <50
    katimaki / <50
    popo01 / "high"
    aspi / ~140
    spooky / >4000
    Leitwolf / <10

    I know, I counted myself twice ;). But given the fact, that very few CFS patients ever got tested, this is yet a very remarkable clustering.

    There are a lot of resources over the net explaining what MBL is. Here just one example
    http://www.congrex.ch/2006/escmidschool2006/pdf/edu_mat_2006_21.pdf

    Essentially it is a universal antibody, binding to mannan molecules on the surface of pathogens. Thus it is relevant for bacterial, fungal, viral und other infections. I personally do believe it's most important for fungal infections, because the specific immune system is otherwise working poorly on those. But whatever the infectious agent in CFS is, MBL will play a crucial role. It even does in AIDS.
    merylg likes this.
  7. eric_s

    eric_s Senior Member

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    Thanks. If somebody finds more labs, please post them. European ones would be best.
  8. eric_s

    eric_s Senior Member

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    I found some here
    http://www.congrex.ch/2006/escmidschool2006/pdf/edu_mat_2006_21.pdf
  9. Jenny

    Jenny Senior Member

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    The 'Jenny' is me Leitwolf. I had this test done by an immunologist at the Royal Free Hospital under the UK National Health Service (so free of charge). It was part of the standard battery of tests done - I'd never heard of it before.

    I wasn't given a figure but I was told that only 1 in 600 people have a level as low as mine. But when I asked whether this deficiency could be relevant to my illness the doc said that if it was I would have had many severe recurrent infections and would be much more ill than I was.

    I'm not very satisfied with that answer so I'm going to probe some more when I go back to the clinic in September.

    I also think this is all very interesting. How can we get more people tested?

    Jenny
  10. Leitwolf

    Leitwolf

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    Hi Jenny

    If the 1:600 figure is true, that corresponds to not detectable. If I was you I would always demand copies of your test results. You may want to check the table above. There, among rougly 400 samples, is only one with <10ng / ml.

    I like the logic of your immunologist. If you had an infection you'd be ill for real, which you are not of course. Because CFS is only on your had, you know. I had to listen to tons of trash like that. Lets not pay attention to these morons..
  11. leela

    leela Slow But Hopeful

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    Wow. I had never heard of this. Here is an interesting link, with an excerpt:
    http://www.bio.davidson.edu/courses/immunology/Students/spring2006/Mohr/MBL.html

    IV. Diseases Associated with Mutations in MBL

    The MBL2 gene encodes mannose-binding lectin (MBL) that is secreted by the liver into the bloodstream (Ohlenschlaeger et al., 2004). Although serum levels of MBL are normally rather low (1500 micrograms/litre), MBL has a crucial role in innate immunity (Turner, 1998). The frequency of this deficiency due to mutations of the MBL2 gene in the general population has been estimated to be between 5 and 10% ( Turner, 1991 ). MBL deficiency arising from mutations and promoter polymorphisms in the MBL2 has been associated with increased risk, severity, and frequency of infections and autoimmunity (Flemming, et. al., 2004).

    Although most individuals with MBL deficiency are healthy, they have an increased susceptibility to certain illnesses. The deficiency has been reported to be particularly common in infants with recurrent respiratory tract infection, otitis media, and chronic diarrhea. The low levels of MBL in young children with recurrent infections suggest that the MB-lectin pathway is important during the interval between the loss of passively acquired maternal antibody and the acquisition of a mature immunologic repertoire (Summerfield et al., 1997).

    MBL deficiency is also associated with non-infectious diseases in adults including systemic lupus erythematosus, rheumatoid arthritis, cystic fibrosis and common variable immunodeficiency. MBL deficiency increases susceptibility to infectious disease. One study that found a significantly higher number of HIV-infected homosexual males were homozygous for variant MBL2 alleles than were high-risk homosexual controls or healthy controls. Although no significant association was found in progression from infection to clinical AIDS, there was a significantly shorter mean survival time after AIDS diagnosis in men carrying variant MBL2 alleles and those with low serum MBL. The increased risks may be associated with increased susceptibility to coinfections (Garred et.al, 1997). MBL-deficiency also poses a problem for other immuno-compromised individuals, such as cancer patients undergoing chemotherapy. In these patients, there was a strong correlation between MBL-deficiency and the occurrence of clinically significant infections. In addition, studies of cystic fibrosis patients found that MBL-deficient patients have a life expectancy 8-years shorter than MBL sufficient individuals, due to increased bacterial colonization of the lung (Trevisiol, 2005).

    If MBL is involved in clearing away bacteria and other pathogens, why is MBL deficiency associated with autoimmune diseases such as lupus and rheumatoid arthritis? The immune system has redundant pathways that all have the same function so that if one is not working well, the immune system can still operate. For example, the classical, MB-lectin, and alternative pathway all make a C3 convertase which leads to oposinzation of pathogens, recruitment of inflammatory cells, and killing of pathogens (see Fig. 4). If the MB-lectin pathway is not working well due to MBL deficiency, the immune system compensates by increasing activation via the other pathways. Most notable is the increase in antibody concentration, used in the classical pathway. Studies have shown an increase in serum levels of IgM antibody concentrations in MBL deficient patients with rheumatoid arthritis. The more antibody, the higher the chance that some antibody will be self-reactive, which is what happens in arthritis( Jacobsen, 2001).

    It is also interesting to note the effect of MBL gene polymorphisms on the susceptibility to infection after liver transplantation because all MBL is hepatically produced. Infection is the primary cause of death after liver transplantation. As transplant patients require immune suppressive drugs in order to insure graft survival, they rely to a great extent on their innate immunity to counteract infections. Studies show the presence of MBL variant alleles in the MBL gene of the donor liver, but not in the recipient, is associated with a strongly increased incidence of clinically significant infections following transplantation in a gene-dose-dependent way. This confirms that serum MBL is produced by the liver and is under strong genetic control. The ability to identify a group of patients severely prone to infection post transplantation is of significant clinical value. In an era of donor supply, donor selection based upon MBL genotype is inconceivable. Patients receiving an MBL-variant liver could benefit from MBL replacement therapy similar to that presently being studied in phase I/II and III clinical studies (Bouwman, 2003).


    V. Therapy for MBL Deficiency

    MBL therapy is an area of current research. Therapy for MBL deficient patients involves giving an intravenous infusion of purified mannose-binding lectin obtained from human donor plasma in an attempt to prevent or ameliorate infections. MBL therapy could be used in three clinical scenarios. Firstly, where MBL deficiency leads to increased susceptibility to disease, MBL replacement could be used to increase resistance to that disease. Secondly, in an acute infection MBL therapy might, by enhancing the immune response, speed the resolution of disease in MBL-deficient patients. However, by analogy with complement deficiencies, a potential hazard of MBL replacement in infection is that it might actually do more harm than good by increasing complement-mediated host damage. Uncontrolled activation of the complement system through the MBL pathway may cause inflammation resulting in tissue damage. Thirdly, MBL therapy could be used to alter the natural history of chronic diseases (Summerfiled, 2003).

    The usefulness of replacement MBL therapy has shown promise in enhancing recovery to bacterial disease. It will take many years and larger numbers of patients to detect significant changes in the natural history of MBL deficiency associated chronic diseases like rheumatoid arthritis. One study followed a cystic fibrosis patient given MBL pooled from human plasma as an intravenous infusion twice a week for a period of 3 months. The patients's clinical condition was stabilized during the treatment period, but was not improved(Garred, et. al, 2002). Future study of MBL therapy should provide more definitive answers to the effectiveness of short-term and long-term therapy.
    merylg likes this.
  12. Mya Symons

    Mya Symons Mya Symons

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    This place here doesn't offer the test in it's index; however, they used to let you e-mail them with the name of a test they didn't have listed and then they would order that test. I am not sure if they still do that, but for anyone who wants to get this MBL test it would be worth a try:

    https://www.health-tests-direct.com/index.aspx?GS=1750085639917


    Is this the right supplement? The description seems somewhat correct in that it lowers T-cell lymphocytes. However, I think it is made from aloe vera?
    http://pureformulas.com/mannan-1-oz-by-deseret-biologicals.html


    ooh ohh - Here is the ELISA you can purchase online:

    http://www.enzolifesciences.com/product-listing/

    It looks like you can buy human Mannon Lectin from here also. Did I get that wrong?

    MBL oligomer ELISA kit
    ELISA, Colorimetric detection | datasheet

    BPD-KIT-029 96 wells 700.00 USD 700.00 USD REMOVE

    Mannan-binding lectin (human), mAb (11C9)
    From mouse. | datasheet

    BPD-HYB-131-11-S 50 g 225.00 USD 225.00 USD REMOVE

    Just realized it is made from mice. Do any of us really want to go that route?
  13. taniaaust1

    taniaaust1 Senior Member

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    Kind of scary that one.
  14. eric_s

    eric_s Senior Member

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    If it's covered by the NHS then that should not be very hard. Just find a large enough group of UK people and then they can get tested for free. I would try asking a UK ME/CFS group. And if that doesn't work, ask around on a forum. I will try to find out if the test is available in Switzerland, if it is, then it should be similarily easy to get people tested as in the UK. If it's only available abroad then health insurers don't like to pay, even though they have to, if the test is necessary.
  15. Leitwolf

    Leitwolf

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    @Mya This is just the ELISA test kit, which is basically always using "mouse derived" antibodys. That has got nothing to do with MBL substitution..
    merylg likes this.
  16. Mya Symons

    Mya Symons Mya Symons

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    I see now. I thought it was a little strange they would be selling this without a prescription.
  17. Leitwolf

    Leitwolf

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    I just wonted to ask whether there is any news on the agenda. I really want to get this checked, not so much for the individual, which is useful, but for CFSlers as a group. This really is a point that could change the faith of us all. If there is an association between MBL deficiency and CFS we can have all that we ever asked for:
    1. its acceptance as a physical disease
    2. a viable treatment for at least a large fraction of us. And it would certainly get easier even for those without MBL deficiency

    I think we should, most of all, get this through to CFS advocacy groups. And there should be some ppl on the board involved in that.
  18. eric_s

    eric_s Senior Member

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    I will see what i can do in Switzerland, i'm involved with this group now. The good thing is that in the Swiss system you have to pay only a little fraction of the bill, if the test is done within the country or if it's done abroad and the insurer accepts that it was necessary and not available domestically. But i'm really very, very overloaded at this moment, so it will take a while.

    I think one should look for a country where there's a health care system that covers all or most of such costs, there it should be rather easy to get a large enough number of people tested. And then contact a group in such a country. Feel free to go ahead and not wait for me.

    Also we should be getting the Blood Working Group's Phase III results within 2 weeks or so and if they confirm XMRV we probably have a much better biomarker. And there have been other physical findings associated with ME/CFS, so i don't know if this one would be the better biomarker, better lead. But it's always good to find another one, i guess.
  19. justinreilly

    justinreilly Stop the IoM & P2P! Adopt CCC!

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    Good luck Leitwolf! It would be great to have pathology for which there is an effective treatment!
  20. Leitwolf

    Leitwolf

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    On the german board we have another person that tested for MBL, which I add to list:

    User / MBL
    Sonnenblume1703 / <50
    katimaki / <50
    popo01 / "high"
    aspi / ~140
    spooky / >4000
    Leitwolf / <10
    Mickybaby / <50

    and we might add Jenny to the list:

    Jenny / ~10


    A cut-off of <140 ng/ml would account for approximately 5% of the healthy population. So we have 6/8 = 75% CFS patients seriously deficient of MBL based on this internet inquiry.

    WE DO NEED THIS RESEARCH TO BE DONE !!!!

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