Monday, 23 January 2012

Spinal fluid oligoclonal bands: are they the secret to uncovering the cause of MS?

Epub ahead of printKorn & Tumani. Patterns of intrathecal autoreactive antibodies in MS using antigen microarrays. Neurology. 2012 Jan 18.  

The role of autoreactive antibodies in MS has received intense attention since the discovery of oligoclonal immunoglobulin (Ig) bands in the spinal fluid of the majority (>95%) of MS'ers. However, many questions remain. We still do not know whether the production of Ig in the brain of MS'ers is an epiphenomenon of CNS autoimmunity, resulting from growth factor-driven expansion of long-lived B cells (the cells that make antibodies) in the meningeal* compartment or whether Ig production from antigen-driven proliferation of B-cell clones contributes to CNS pathology. CSF Ig from oligoclonal bands is produced by CSF B lineage cells and primarily recognizes epitopes of multiple neurotropic viruses and Epstein-Barr virus antigens.  However, antimyelin antibodies also occur in the serum and CSF of patients with MS.

*meningeal or meninges = the layer of membranes to covers the brain and spinal cord


"In my opinion the secret to the cause of MS lies in uncovering the antigen or proteins against which the antibodies are directed. In disease with known causes (e.g. viral encephalitis) that have oligoclonal IgG bands, the bands react to proteins from the causative agent."

"Cosimo Maggiore in our group is completing a PhD to try and delineate the antigens against which OCBs in MS'ers react. The project has a long way to run. Let's hope he gets there."

19 comments:

  1. Prof G,

    "Secret to the cause of MS lies in uncovering the antigen or proteins against which the antibodies are directed."

    Silly question, why can't researchers focus on this and crack this issue? Is the problem technology - not advanced enough to undertake this analysis?

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  2. Is MS, in your opinion, a result of dangerous T cells, or is it because of dangerous B cells?

    Drugs like fingolimod attack T cells, don't they? What drugs counter B cells? Is RRMS more to do with T cells and SP/PPMS a result of B cell damage?

    Also, how long have clinicians known about oligoclonal bands as a signifier of MS? Do people without MS also have oligoclonal bands floating around in their cerebral fluid?

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    Replies
    1. Yes I do and I had mumps encephalitis as a child. I was originally dx as having ms but with no progression was eventually dx with genetic Ehlers-Danlos Syndrome.

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  3. Is it true that the type of OCBs is constant for each MS patient? How wide is the variety of OCB types in MS? What does this mean in terms of MS causation?

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  4. Re "uncovering the antigen or proteins against which the antibodies are directed": Isn't that what Mouse Doctor's post today is about?
    http://multiple-sclerosis-research.blogspot.com/2012/01/research-msers-react-againist-myelin.html

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  5. The following article entitled "B cells and Autoantibodies: Complex Roles in CNS Injury" states that B cell activation and production of antibodies happens also as a consequence of CNS injury.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2933277/

    Correct me if i am wrong, but this means that the OCBs in MS do not necessarily imply a reaction to some pathogen, but could very well be the aftermath of some kind of brain or spinal injury.

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  6. Prof G,

    I'm a big fan of the EBV theory. Will the Charcot Project throw any light on whether the immune response is against EBV?

    VV,

    Can't you do something useful like solve the Greek debt problem? Are you attending the research day on Saturday?

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  7. "Is MS, in your opinion, a result of dangerous T cells, or is it because of dangerous B cells?"

    As an immunologist I would say both can be dangerous, some people may argue it is something else.

    "Drugs like fingolimod attack T cells, don't they? What drugs counter B cells?"

    Fingolimod attacks both T and B cells, although it may be more active in blood than in cerebrospinal fluid.

    (http://www.neurology.org/content/76/14/1214.abstract)

    Drugs such as alemtuzumab and notably ocreluzumab/rituximab target B cells

    "Is RRMS more to do with T cells and SP/PPMS a result of B cell damage?"

    Some think that progressive MS may be linked with B celll activity but to date depletion of B cells at least from the blood does not appear to control progression. On balance I think that progression is neither a problem of T or B cells but is a problem of macrophages and demyelinated nerves
    If you hunt through the blot there are some alternative explanations

    On the other hand these treatments inhibit relapsing MS. Some people think that the action of T cells are every thing, but there is not alot of hard evidence to support this.

    Whilst B cells may have a role in MS not all anti-B cell drugs are the same some inhibit MS others make MS worse

    "Also, how long have clinicians known about oligoclonal bands as a signifier of MS? Do people without MS also have oligoclonal bands floating around in their cerebral fluid? "

    Prof G will probably know the history of oligoclonal bands but along time but they do occur in other disease besides MS

    http://en.wikipedia.org/wiki/Oligoclonal_band

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  8. "Will the Charcot Project throw any light on whether the immune response is against EBV?"

    All will be reveiled on Saturday, but we will be adding abit more detail soon, but EB is part of the equation

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  9. All will be revealed on Saturday

    Prof Mouse,

    I can't wait that long. Have a couple of pints of real, put on your Black Sabbath album, and let me know what's going to be revealed (just between you and me).

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  10. Despite rocking with a pint you'll still will have to wait as Prog G down under has not finished his talk, so I don't know what he'll say may be only part of the story.

    http://multiple-sclerosis-research.blogspot.com/p/charcot-project.html

    However a radically different way to approach MS so sceptics be prepared

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  11. P.S. It is not my project...... so best let others blow their trumpet

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  12. From
    "Roles of autoantibodies in central nervous system injury."
    http://www.ncbi.nlm.nih.gov/pubmed/21616038

    "Preliminary proteomics analyses indicate that >50 different self-proteins are targeted by SCI autoantibodies (unpublished data)."

    SCI=Spinal Cord Injury

    So, there is no need for mad B cells or viruses of some kind to account for the autoantibodies. MS patients may suffer from CNS injury. Any investigation into that?

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  13. Retorical questions usually need no answers

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  14. So you are absolutely certain that there is no CNS injury in MS. I'll keep that for future reference.

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  15. So you are absolutely certain that there is no CNS injury in MS.

    Please read the many posts on the blog to get your answer.

    The Question is not useful.

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  16. Re: "Also, how long have clinicians known about oligoclonal bands as a signifier of MS? Do people without MS also have oligoclonal bands floating around in their cerebral fluid?"

    The immunoglobulin response in MS was discovered in the 1940s; it was shown to be oligoclonal in teh 1960s.

    Yes, some normal people have OCBs; presumably as a result of an episode of encephalitis. You may be interested to know that about 30% of siblings of MS'ers have OCBs and only 2.5% develop MS. This is one of the characteristics of the MS endophenotype that we are very interested in.

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  17. If drugs look to control B and T lymphocytes in blood what role does blood brain barrier play?

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  18. Donating plasma may stimulate the body to produce antibodies if one has had EBV. If you're consistantly stressed throughout life (maybe that's why women are twice as likely to get ms) the body may finally decide to see the inflamed nervous system response to stress as a threat and release the antibodys necessary to attack the nerves in an attempt to destress you.

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