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Breakthrough opens door to safer lupus drugs

Discussion in 'Other Health News and Research' started by Bob, May 15, 2015.

  1. Bob

    Bob

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    England (south coast)
    Online article - I haven't found the associated published research.

    Breakthrough opens door to safer lupus drugs

    May 14, 2015
    Monash University
    http://www.sciencedaily.com/releases/2015/05/150514095749.htm

    Extract from article:
    Read full article here:
    http://www.sciencedaily.com/releases/2015/05/150514095749.htm
     
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  2. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    It seems as if they are referring to TACI knockout mice with maybe a transgene for high BAFF as well. I am not sure this is a very useful model for human lupus, which is not due to genetic engineering. (Nor is it due to high BAFF even when it happens.) Nevertheless, we have been trying to get people to focus on the potential of using TACI-Ig and other anti-BAFF strategies in RA and lupus for fifteen years - maybe in tandem with an anti-CD20 like rituximab. What it really needs is for someone to have the courage to do some good human trials. Unfortunately doing trials in lupus is tricky because of heterogeneity and the instability of the clinical state. But it will get done soon I think. If the animal model people are working on it too then maybe it will help.
     
  3. Daffodil

    Daffodil Senior Member

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    they are looking at BAFF antagonists for sarcoidosis and some autoimmune neurological diseases too....

    if BAFF is increased in these diseases, and blocking BAFF makes one more susceptible to bacterial infections, could it be that BAFF is somehow increased by existing bacterial infection that is driving the autoimmune disease?

    sorry, totally speculating here..i know nothing about this stuff.
     
  4. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    BAFF is not actually increased in these diseases as far as I know. It is only in the animal models. BAFF levels are normal in RA and can be high in some lupus cases but by no means all. What is almost certainly true is that BAFF is necessary to keep the autoimmune process rolling - but normal levels will do.

    The interest in BAFF in sarcoid is interesting. A French group showed years ago that sarcoid patients have autoantibodies to peanut agglutinin receptor, suggesting that it is a typical B cell mediated autoimmune process. Very few people seemed to notice that but maybe it has now caught on.
     
  5. SaraEngland

    SaraEngland

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    @Jonathan Edwards, a scientist I've spoken to said that BAFF is elevated in ME, and that a study will be published soon. April is normal.

    How could one interpret this? What are your thoughts?
     
  6. duncan

    duncan Senior Member

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    Speaking of sarcoidosis...Sorry, couldn't resist. :D

    Send to:


    Chin Med J (Engl). 1992 Jul;105(7):560-3.
    Borrelia burgdorferi infection may be the cause of sarcoidosis.
    Hua B1, Li QD, Wang FM, Ai CX, Luo WC.
    Author information
    Abstract

    Serum antibody to Borrelia burgdorferi was measured in 33 patients with sarcoidosis which was confirmed clinically and pathologically. The results showed that 81.8% of the patients were positive for anti-B. burgdorferi antibody. In addition, a strain of B. burgdorferi was isolated from a patient's blood. Fifteen patients received ceftriaxone 2g per day or penicillin 12 million U per day. The antibody titers of the patients decreased to nearly normal levels rapidly. Serum angiotensin converting enzyme (SACE) turned to normal range after the treatment. According to the findings mentioned above, we consider that B. burgdorferi infection may be the cause of sarcoidosis and sarcoidosis might be a specific type of Lyme disease.

    PMID:
    1333393
    [PubMed - indexed for MEDLINE]
     
  7. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    It would be very interesting if BAFF was high in ME.

    But the quote is factually wrong. BAFF is high in lupus but not in RA and not as far as I know in other diseases. Moreover, people with lupus do not in fact have more antibodies than other people as a rule. They sometimes have less. The important thing is that they have the wrong antibodies. I don't think there is any evidence that the high BAFF causes the lupus. It seems much more likely that the lupus causes the high BAFF.

    And of course if BAFF was high in ME then presumably it would not be raising antibody levels because they are not high in ME - but it might mean something much more interesting.
     
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  8. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Interesting that there is no mention of the sarcoid getting better. Which is presumably why people still have sarcoidosis 23 years later - oops, 24 years later!
     
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  9. duncan

    duncan Senior Member

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    @Jonathan Edwards , are you speaking of specific antibodies when you say they are not high in ME, because as I understand it, pwME frequently report elevated antibody levels?

    And yes, I do realize this is an old study. Then again, that is characteristic of both the ME and Lyme communities - research efforts and published studies that often don't get followed-up on.
     
  10. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    I was talking of total antibody - total immunoglobulin levels. If BAFF caused autoimmune disease by stimulating antibody production the high BAFF ought to raise total antibody levels. In reality things are more complicated. I am not actually aware that we know that PWME have higher antibody levels to anything much in fact. It is another of those things that if we actually knew about we would have a biomarker and we don't.

    The sarcoidosis research community, and in particular my colleague Donald Mitchell, would have followed up anything on sarcoid that held water. People have been throwing penicillin and other antibiotics at sarcoid cases since the 1950s. They never got better as far as I know. (And even these Chinese chaps say nothing about them getting better in their abstract.)
     
  11. duncan

    duncan Senior Member

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    You never heard of elevated levels of HHV-6, EBV, CMV, enteroviruses, etc in pwME? (And Montoya has spoken to total IgG levels, I believe.) That levels of antibodies to multiple pathogens are commonly higher, but the causal link remains unproven? That certain ME/CFS clinicians and researchers have their own pet theories as to which pathogen of the mix may be to blame?
     
  12. deleder2k

    deleder2k Senior Member

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    The information about BAFF is from Olav Mella and Øystein Fluge made at a conference in Norway. Some other key points:

    They say that analysing the biobank material is very important. They are collaborating with Charite, UCL London, Arizona State University, Immunological Department at the Oslo University Hospital, Insitute of Biomedicine Bergen - and analysis done by Haukeland will give important insight in mechanisms that drive the disease.


    - In addition to BAFF they mentioned that clinically they see two groups of patients: hyperimmune patients and patients prone to infection.

    - ME patients as a group has TH 2 immunological profile (pro inflammatory)

    - Time to remission after anti cd20 looks like autoantibodies are beeing washed out. Current cyclo study show that T-cells could be involved in the pathogenesis as well
     
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  13. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Indeed I have heard of all this. But where are the reliable published studies? I have spent my life convincing myself and having PhD students try to convince me that patients have this or that difference from controls. But as the years went by I realised that nearly always when you re-compare blinded samples you come out with a lemon. Science is much too easy to get wrong. We need to look at blinded samples from the biobanks with their matched controls and see if there is anything in any of this. Selection bias is like Araldite on your fingers. It sticks to everything and the only solution is to start again and make sure you touch nothing.
     
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  14. duncan

    duncan Senior Member

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    Yes, there is something to be said about selection bias.

    I am pretty sure there are loads of publications that support elevated antibody levels in pwME, but I cannot think of any off the top of my head.

    But as a person with ME, I have elevated values for all the usual suspects. So I conform to that characteristic.

    Yes, that is anecdotal. I suspect, though, you'll find many similar anecdotes on this forum.
     
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  15. BurnA

    BurnA Senior Member

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    Was this a recent conference ?
    Did they put any significance or elaborate on the two clinically different groups of patients ?
    Thanks.
     
  16. deleder2k

    deleder2k Senior Member

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    As far as I know this was at a conferance in Bergen.

    I wasn' there, so I don't know what they told the audience. I only have the powerpoint which is in Norwegian.

    I'm looking forward to the BAFF study.
     
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  17. BurnA

    BurnA Senior Member

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    Thanks.
    Here's a question ....
    If rtx only works on b cells but they suspect t cells could be involved from the cyclo trials, does this suggest there are rtx non responders responding to ctx ? Or is there another way for them to come to this thinking ? Must they have spotted some differences between patients from the rtx trials and the ctx responders ?
     
  18. deleder2k

    deleder2k Senior Member

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    I know that one or more subjects that were classified as not responding in the RTX study have responded. I don't know how many, or nor do I have details about the response.

    Hopefully a major proportion of non responders to RTX respond to cyclo.
     
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  19. RL_sparky

    RL_sparky Senior Member

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    Has this study been started?
     
  20. deleder2k

    deleder2k Senior Member

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    The study will be published soon, so I guess that means it has started :)
     
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