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Fluge & Mella: Serum BAFF & APRIL Levels, T-Lymphocyte Subsets, and Immunoglobulins after B-Cell...

Discussion in 'Latest ME/CFS Research' started by mango, Aug 18, 2016.

  1. mango

    mango Senior Member

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    Serum BAFF and APRIL Levels, T-Lymphocyte Subsets, and Immunoglobulins after B-Cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Myalgic Encephalopathy/Chronic Fatigue Syndrome
    • Sigrid Lunde,
    • Einar K. Kristoffersen,
    • Dipak Sapkota,
    • Kristin Risa,
    • Olav Dahl,
    • Ove Bruland,
    • Olav Mella,
    • Øystein Fluge
    Abstract
    Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is a disease of unknown etiology.

    We have previously suggested clinical benefit from B-cell depletion using the monoclonal anti-CD20 antibody rituximab in a randomized and placebo-controlled study. Prolonged responses were then demonstrated in an open-label phase-II study with maintenance rituximab treatment.

    Using blood samples from patients in the previous two clinical trials, we investigated quantitative changes in T-lymphocyte subsets, in immunoglobulins, and in serum levels of two B-cell regulating cytokines during follow-up.

    B-lymphocyte activating factor of the tumor necrosis family (BAFF) in baseline serum samples was elevated in 70 ME/CFS patients as compared to 56 healthy controls (p = 0.011). There were no significant differences in baseline serum BAFF levels between patients with mild, moderate, or severe ME/CFS, or between responders and non-responders to rituximab.

    A proliferation-inducing ligand (APRIL) serum levels were not significantly different in ME/CFS patients compared to healthy controls at baseline, and no changes in serum levels were seen during follow-up.

    Immunophenotyping of peripheral blood T-lymphocyte subsets and T-cell activation markers at multiple time points during follow-up showed no significant differences over time, between rituximab and placebo groups, or between responders and non-responders to rituximab.

    Baseline serum IgG levels were significantly lower in patients with subsequent response after rituximab therapy compared to non-responders (p = 0.03).

    In the maintenance study, slight but significant reductions in mean serum immunoglobulin levels were observed at 24 months compared to baseline; IgG 10.6–9.5 g/L, IgA 1.8–1.5 g/L, and IgM 0.97–0.70 g/L.

    Although no functional assays were performed, the lack of significant associations of T- and NK-cell subset numbers with B-cell depletion, as well as the lack of associations to clinical responses, suggest that B-cell regulatory effects on T-cell or NK-cell subsets are not the main mechanisms for the observed improvements in ME/CFS symptoms observed in the two previous trials.

    The modest increase in serum BAFF levels at baseline may indicate an activated B-lymphocyte system in a subgroup of ME/CFS patients.

    http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161226
     
  2. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    Just finished reading, had been waiting for this one. Incredibly thorough as usual from Fluge & Mella.
    Disappointingly they found no clear links with bAFF and rituximab-response, or disease severity. Still the modest statistically difference in baseline serum levels compared to controls "supports the presence of a chronically activated B-lymphocyte system", and i guess now hypotheses should investigate what place in a theorized disease mechanism this increased bAFF may have.

    Maybe the most important findings here, is the negative findings.
     
    Comet, Ninan, L'engle and 5 others like this.
  3. Kyla

    Kyla ᴀɴɴɪᴇ ɢꜱᴀᴍᴩᴇʟ

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    I was a bit confused to see that they measured NK-cells and subset numbers but not NK-cell activity - which is what comes back as significantly abnormal in previous studies.
    Am I reading this wrong?
    or maybe they weren't able to measure as this test is time sensitive? (ie- they couldn't use stored samples from the previous studies)
     
    L'engle, justy, Valentijn and 2 others like this.
  4. Kati

    Kati Patient in training

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    It's disappointing they didn't measure NK cell function. It's a time sensitive test indeed but it's primarily expensive, which may have been a deterrent.
     
  5. Snow Leopard

    Snow Leopard Hibernating

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    A key point to be made is that the results of this study are not inconsistent with autoimmunity being a factor for a subset of patients.

    I personally don't believe any T-Cell or NK Cell issues are causative in ME, so those results don't worry me at all...
     
    Justin30, Ninan, L'engle and 4 others like this.
  6. Sasha

    Sasha Fine, thank you

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    Ninan, Theodore, Gingergrrl and 2 others like this.
  7. sarah darwins

    sarah darwins I told you I was ill

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    Thank heavens you said that, Sasha. I thought it was just me :p
     
  8. A.B.

    A.B. Senior Member

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    It seems to be another piece of information telling us that this disease is different from regular autoimmune disease.
     
    Webdog likes this.
  9. Snow Leopard

    Snow Leopard Hibernating

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    How? Did you read the paper?
     
  10. Gingergrrl

    Gingergrrl Senior Member

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    "Over my head" doesn't even capture the level this is above me but am hoping someone can summarize or explain it!
     
    Theodore, justy and Sasha like this.
  11. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    What I wonder is that maybe some of these immune cells simply are dysfunctional, and that the amount of them don`t matter.
     
  12. A.B.

    A.B. Senior Member

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    I wasn't sure how to best express the idea. The disease seems to be autoimmune but at the same time seems to be different from other known autoimmune diseases.

    The authors write that "The data presented in this study cannot lend support to any specific disease mechanism."
     
    MeSci likes this.
  13. Gijs

    Gijs Senior Member

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    Elevated B-lymphocyte factor of the tumor necrosis family (BAFF) or activation could be due to food and gut problems seen in ME patiënts. More proof for Lipkin and Hornig. But still it could be autoimmunity.
     
  14. Gingergrrl

    Gingergrrl Senior Member

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    That seems to summarize my illness whatever title it may ultimately have.
     
    Webdog and MEMum like this.
  15. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    Well with regards to bAFF levels and rtx-treatment, at least seemingly different from lupus. They pointed out that elevated bAFF-levels are seen in many other autoimmune diseases as well.
     
    MEMum likes this.
  16. Bob

    Bob

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    This seems to be almost a null study. Some significant but slight or modest differences but nothing that stands out as screaming that it deserves further attention, as far as I understand it?
     
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  17. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    I would agree if it wasn`t for the results from the rtx-trials.. These results don`t scream, but maybe we have to listen to the whispers?
     
    Valentijn likes this.
  18. user9876

    user9876 Senior Member

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    Null studies are important as they help say where not to look.
     
    cfs6691, MeSci, Ninan and 11 others like this.
  19. Snow Leopard

    Snow Leopard Hibernating

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    Okay. But the key is that the results don't disprove it either - null results on the above tests (though BAFF was positive), have been obtained for other autoimmune diseases.
     
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  20. Justin30

    Justin30 Senior Member

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    I was reading like usual the otherday and came accross a piece of literature that discussed CD8 cells...completely busting through the GI tract and leading to autoimmunity, etc. Not literally but I guess destroying the integrity or something like that...

    I was kinda blown away. Wish I had saved it.

    But got me thinking how many diseases AI, HIV, Viruses, Bacteria, etc. Result in this....

    I had a weird feeling like why are so many studies just left and not followed up...

    The result was AI Neuro Disease.
     
    natasa778 likes this.

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