Thursday, 24 November 2011

Research:Immune attack of myelin may play a small influence,

Menge T, Lalive PH, von Budingen HC and Genain CP Conformational epitopes of myelin oligodendrocyte glycoprotein are targets of potentially pathogenic antibody responses in multiple sclerosis. Journal of Neuroinflammation 2011, 8:161 (17 November 2011)

BACKGROUND:Myelin/oligodendrocyte glycoprotein (MOG) is a putative autoantigen in multiple sclerosis (MS). Establishing the pathological relevance and validity of anti-MOG antibodies as biomarkers has yielded conflicting reports mainly due to different MOG isoforms used in different studies. Because epitope specificity may be a key factor determining anti-MOG reactivity we aimed at identifying a priori immunodominant MOG epitopes by monoclonal antibodies (mAbs) and at assessing clinical relevance of these epitopes in MS.

METHODS:Sera of 325 MS patients, 69 patients with clinically isolated syndrome and 164 healthy controls were assayed by quantitative, high-throughput ELISA for reactivity to MOG isoforms, and quantitative titres correlated with clinical characteristics.

Structure of MOG

RESULTS:In the majority of human samples anti-MOG levels were skewed towards low titers. However, in 8.2 % of samples high-titer anti-MOG antibodies were identified. In patients with relapsing-remitting MS high-titer anti-MOG IgG correlated with disability (EDSS; Spearman r=0.574; p=0.025).

CONCLUSIONS:Thus high-titre reactivity likely represents high-affinity antibodies against pathologically relevant MOG epitopes, that are only present in a small proportion of patients with MS.

"MOG is one of the few myelin targets that is available to attack by antibodies. In animals immune responses to this protein can drive relapsing neurological attacks and antibodies can induce demyelination. This study suggests that such antibodies present in MS could contribute to problems. However, that these antibodies are not ubiquitous (common to every one) suggests that autoimmunity to this protein cannot fully account for the problems of MS. However it should be said that other studies have reported a higher incidence of anti-myelin antibodies. It is feasible that different people will react to different myelin proteins, as is known and is likely to occur. However, it may suggest such that antibodies can be produced as a consequence of other damaging entities that could trigger this autoimmunity

Do I think that antibodies that react with targets within the CNS are a problem in MS. Well yes I do and I'm pretty sure of that because we can take antibodies for MSers and inject them into animals and see undesirable effects.


16 comments:

  1. MouseDoctor,

    Fascinating post (IMO), but I predict (sadly)nthe conclusions of this study will be twisted and used as as gristle for ulterior motives. And thank you for the very informative Slate article regarding using animal models for MS. Are the mice used in MS research all transgenic?

    Thank you for the Thanksgiving cheers as well. As a fellow heavy metal fan, I salute you with a double corna. I will be happily looking forward to more of the "same old, same old" from Prof G and the team. Thanks for keeping this blog up!

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  2. No not all animals used in MS research are transgenic.

    Our main stay that we have worked with for twenty years is non-transgenic.

    However we have made a new mouse model that is transgenic which has some advantages both for us and also for the animal too.

    Transgenics whether transgenic worms, flies or mice have been invaluable tools to help understand biology

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  3. Dear Maria
    "I predict (sadly)the conclusions of this study will be twisted"

    I have changed the end of the original post abit, since you posted butyou may be right.

    I am pretty sure however that such type of autoimmune responses have some part to play in MS. Responses to therapy clearly tell us there is an immune problem.

    Also MOG is just one of many potential autoantigens and animal studies clearly show that different indidivuals respond to different targets and that these change over time

    Although I'm not an myelin basis protein fan others think this is the importnat target. Others would say proteolipd protein, then there is CNPase, myelin oligodendrocyte specific protein, myelin associated glycoprotein, neurofascin etc, etc, etc and of course alpha B crystallin, which was reported to be a better target than myelin and was a response that MSers respond to.

    Then there are other non-myelin proteins also.

    In Team G we have many different views about role of autoimmunity in MS

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  4. Re "...we can take antibodies for MSers and inject them into animals and see undesirable effects."

    What happens if they are injected into humans without MS?

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  5. "What happens if they are injected into humans without MS?"

    You wouldn't be allowed to do this!!

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  6. You said "What happens if they are injected into humans without MS?"

    Please take one step back and think for a second, no a nano second, about what you have just written.

    If you give this much level of thought into your comments, then frankly no one wants to hear them. I don't. I am shocked you obviously believe in the Josef Mengele school of Research.

    Please never, ever, ever, ever put yourself forward for any form of ethical review panel.

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  7. Can't this happen in blood transfusion when the blood donor has MS?

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  8. I'm sorry to be creepy but the question of injecting MS anibodies into non-MS'er has also piqued my curiosity.

    Is that all it would take to give someone MS? Is it really that easy? If it is then the disease seems less complex than I originally thought.

    I'm not being sick Danger Mouse, just interested I guess.

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  9. Yes, I am interested in knowing this also. Can you make a healthy person develop MS just by injecting them with MS anitibodies?

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  10. "Can you make a healthy person develop MS just by injecting them with MS anitibodies?"

    In my opinion No! However it would be very unethical to try! Just think for two nanoseconds (two thousandth of a second)

    Maybe G, as someone more interested in causative agents of MS can comment.

    BLOG

    I am sorry the first post was ?,the reposte was????????.

    I am sorry if I seem rude, but should we be experimenting on people (who knows next prisoners) with dangerous chemicals? I think ethical considerations say no.

    Even if the blood was full of damaging antibodies, the likeihood that it causes problems in healthy people is small, because the antibodies do not enter the brain, because in healthy people antibodies generally do not enter the brain. This is where the damaging events wouls occur in MS.

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  11. I'm NOT suggesting an experiment to find out, but antibody injection must have happened many times when undiagnosed MSers donate blood. And blood from people with other autoimmune diseases will also have dangerous antibodies.

    Suppose injected antibodies did somehow reach the brain, I guess it could cause lesions & symptoms. Is there a link to the 'disseminated in time' requirement for MS diagnosis? And is there a chance that it causes permanent MS?

    I did a little browsing and found that in Singapore anybody with any autoimmune disease is ineligible to give blood. Most countries do not have such a clear policy.

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  12. Dear Anon 4.15

    If you are in need of a blood transfusion, which is the only time you are going to need blood, then I suspect that the benefits outweigh the risks.

    Antibodies in the transfused blood will probably be at low levels and will be diluted by the recipients own blood circulation and this will reduce the impact. If you need alot of blood then it will be diluted by the other donations of blood used.

    The chance of the dangerous antibody reaching its target i.e to get into the brain would be low.
    Because the blood brain bariier excludes antibodies.

    If it did get into the brain, it may cause effects, but for many damaging antibodies to have effects (such as the MOG antibodies in the post) requires the presence of other molecules such as complement (an immune mediator) which would have to also get in the brain for the antibody to have an effect. So again this lowers risk

    Even if they did have an effect once the antibodies disappear from the blood and the brain, which will happen naturally, the effect would go and the brain would no doubt repair any damage.

    The presence of transient amounts of antibody would not be sufficient to maintain disease even if this was the cause of disease, as you would need the antibody producing cells to sustain the response. These cells are short-lived and would be rapidly killed off via transplant rejection following any transfusion. You may also require T cells to help the B cells produce antibodies and again these would be rejected following transfusion.

    Furthermore even in MS, many lesions go unnoticed (as evidenced by the MRI) so again this, would limit the the risks

    Therefore if I need blood I will be happy to recieve a transfusion
    and so we must be grateful to the people who donate their blood to help save others.

    PS For those of you in the UK you may have seen the BBC this week about the benefits of blood transfusions for saving injured soldiers in Afganistan. The surgeons have been experimenting with blood:plasma mixes and this has helped to increase the survival rate of injured. Some of those guys come from our Hospital and if fact come from our department.

    PPS. The best way to show undesirable effects of antibodies experimentally it first to concentrate the antibodies and then
    to directly inject them into the brain. Now I hope you are not suggesting that we do this experiment in people.

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  13. Regarding antibodies in the CNS I thought their presence was one factor that Prof G thought possibly relevant to progession as none of the current drugs can cross the barrier and kill them- hence the interest in Baminercept. If they die off naturally and the immune system has been 're booted' by something like alemtuzumab, surely over time they will be gone, unless the new immune system continues to produce 'bad' antibodies? Are these the reason why some MSer's with few initial relapses can sometimes go on to develop SPMS?

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  14. Dear Anon 9:33
    You are B cells and antibodies make one possible mechanism behind progression. As we have also mentioned previously in the blog there are others, I even saw some experimental data on hypoxia presented at a meeting.

    One hope with immune modulators is that the immune system will be rebooted and the antibody responses should go. However we have to see if the ones in the brain (such as the oligoclonal bands made by antibodies) go also, as many of the treatments may not get into the brain.

    Good comment and I am sorry if I was ranting in the above posts, by sometimes the reasons behind questions are just too cryptic.

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  15. I know this is an old post but following up on Mousedoctor's comments, would it be appropriate for an otherwise healthy person w/ MS to donate blood. I think based on the comments, the answer would be yes?

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  16. Re: "I know this is an old post but following up on Mousedoctor's comments, would it be appropriate for an otherwise healthy person w/ MS to donate blood. I think based on the comments, the answer would be yes?"

    No. MS'ers are not allowed to donate blood. We don't know the cause of MS and if it was due to a virus blood donation could transmit the disease. However, this has not been shown to occur in reality and is therefore unlikely to occur. Because of this guidelines vary across the world.

    In the UK you should not give blood; please see:

    http://blood.co.uk/pdf/publications/donor_spr2004.pdf

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