Sunday, 13 December 2015

Still hunting for the Autoimmune target

Willis SN, Stathopoulos P, Chastre A, Compton SD, Hafler DA, O'Connor KC. Investigating the Antigen Specificity of Multiple Sclerosis Central Nervous System-Derived Immunoglobulins.Front Immunol. 2015 Nov 25;6:600. eCollection 2015.

The central nervous system (CNS) of patients with multiple sclerosis (MS) is the site where disease pathology is evident. Damaged CNS tissue is commonly associated with immune cell infiltration. This infiltrate often includes B cells that are found in multiple locations throughout the CNS, including the cerebrospinal fluid (CSF), parenchyma, and the meninges, frequently forming tertiary lymphoid structures in the latter. Several groups, including our own, have shown that B cells from distinct locations within the MS CNS are clonally related and display the characteristics of an antigen-driven response. However, the antigen(s) driving this response have yet to be conclusively defined. To explore the antigen specificity of the MS B cell response, we produced recombinant human immunoglobulin (rIgG) from a series of expanded B cell clones that we isolated from the CNS tissue of six MS brains. The specificity of these MS-derived rIgG and control rIgG derived from non-MS tissues was then examined using multiple methodologies that included testing individual candidate antigens, screening with high-throughput antigen arrays and evaluating binding to CNS-derived cell lines. We report that while several MS-derived rIgG recognized particular antigens, including neurofilament light and a protocadherin isoform, none were unique to MS, as non-MS-derived rIgG used as controls invariably displayed similar binding specificities. We conclude that while MS CNS resident B cells display the characteristics of an antigen-driven B cell response, the antigen(s) driving this response remain at large.

So when you have a good idea other people are having it at the same time to exploit technology so you get a series of papers saying the same thing (hopefully), one gets their first and the others cry in their soup at being pipped to the post. These guys have been pipped

So in this post they have taken B cells from MSers brains and then made the antibodies that they can produce and yes they dont react with the myelin. This was seen before. Some respond to neurofilament which maybe a consequence of damage rather than an initial cause. However they find similar specificies in controls so they can't say what the autoantigen is?. Maybe there is no autoantigen because MS is not an autoimmune disease. However we know that some of these antibodies are pathogenic notably anti-neurofilament antibodies.

14 comments:

  1. From what I then understood the neuroaxonal loss of neurofilament, releasing them by CNS, is could that be impulssionando this autoimmune response? If it is well founded the big problem would be to discover the cause of this loss, which would cause inflammation or not?

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  2. After years and years of looking for an autoantigen with no results maybe they will never find it. It seems logical to me that the body would need autoreactive immune cells to sacrifice healthy cells in the proximity of diseased cells to ensure all of the disease is erraticated.

    This is the same logic when one undergoes surgery for a cancer for example. The tumor is removed but also some of the normal looking tissue surrounding the tumor is sacrificed to ensure all of the cancer is eliminated.

    The sympathetic nervous system has control over the immune system to shut it down. Why would every other system in your body be governed by the nervous system, except the immune system?

    Those researchers who are studying the neuri-immuno interactions are the best bet to find a cure for MS as well as many other diseases that appear to be autoimmune in nature.

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  3. "Still hunting for autoimmune target............" Happy hunting and good luck. No auto antigen in MS has been found after all these years should tell the researchers that it doesn't exist.

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    1. I dodn't agree but if you don't look in the right way you are not going to find them

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    2. Mouse, this is my feeling, too - can you elaborate?

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    3. Still looking for the Holy Grail, Sasquatch, Loch Ness Monster, honest politician (insert you're own unattainable item). It's hard to believe that everyone is "looking in the wrong way". I give the highly regarded academic institutions, including Barts, the benefit of the doubt that they know how to find the elusive auto antigen(s). Until proven otherwise, MS is an inflammatory disease of the CNS with an unknown etiology. People should refrain from labelling MS an autoimmune disease until it (antigen) is found. Immunology texts usually have a question mark after MS when describing autoimmune diseases.

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    4. "Hard to believe that people are looking in the wrong way"....I suggest you look for people who are doing this type of stuff and then you will find out they are doing it in the wrong way. If you do experiments with blinkers and by numbers you mess up...sad but true.

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    5. So why hasn't team G found it yet? If you know that everything they are doing is wrong, put your money where your mouth is and make a contribution.

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    6. Firast it needs to be someone elses money:-) as I have no cash, no grants no cure...


      You can only do so much and you can fight the tide or not but we don't need to know what the autoantigen is, as any two people will be different.

      Anyway we have done it, put Mercks money where our mouth was and maybe we cured autoimmunity.

      However we decided to stop the study after it was too slow to recruit and time moved on and we felt we could not put people at risk for an experiment as alternatives came around.. n=1 is meaningless. Maybe we should publish in 2016?

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    7. But if you really found the autoantigen(s) it seems to me you would be vigorously pursuing this. If you have something to publish by all means do so.

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    8. You absolutely should publish!

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    9. Our control of autoimmunity was to stop neutralising beta interferon antibodies where we knew the autoantigen. TWas it a fluke...who knows. Thhat is why we stopped as alternatives came along

      However our apporach to MS means we do not need to know what the autoantigens are as long as they are in oligodendrocytes. We will publish this approach next year hopefully.

      However getting a GMP facilitie is making a new company.

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  4. I kinda agree, I am missing a bit of creative thinking here. What is the solution? If you cannot find it by going down the route of scientific analysis, maybe the solution is to create a model how it could work and then look for evidence? Not saying scientists are stupid, but certainly a bit predictable.

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    1. I think Alpha B crystallin was a good oppertunity to address this, but I feeling this chance has no gone. You can thank pharma for that one.

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