Research: B cell survival factors in relapse

R
EpubWang H et al. Cerebrospinal Fluid BAFF and APRIL Levels in Neuromyelitis Optica and Multiple SclerosisPatients During Relapse.J Clin Immunol. 2012 May 30. [Epub ahead of print]

BACKGROUND: BAFF (B-cell activating factor of the tumor necrosis factor family) and APRIL (a proliferation-inducing ligand) are two of the major survival factors for B cells. Many studies have shown that BAFF levels were elevated in MSers. However, whether the levels of CSF BAFF/APRIL increased in NMOers was still unclear.


OBJECTIVE: To measure the CSF (spinal fluid) BAFF and APRIL concentration of in NMOers, and explore their relationship with disease activity in NMO.


METHODS: CSF BAFF and APRIL was measured by an enzyme-linked immunosorbent assay (ELISA) in NMOers (n = 22), MSers (n = 18) and controls (n = 14).

RESULTS: Concentration of BAFF and APRIL in NMOers were significantly higher than in MSers and controls. CSF BAFF and APRIL levels in controls were also lower than MS. Both NMO and MS revealed an increased disease disability with increased CSF BAFF. CSF APRIL was associated with EDSS scores in NMO, but not found in MSers.

CONCLUSIONS: BAFF/APRIL system considered important for aggressive B cells and T-cell responses, and may stimulates B cells and T cell activation in acute relapse of NMO and MS. In NMOers, CSF BAFF and APRIL may be key factors of B cell immune response and reflect disease severity.



“BAFF and APRIL are immunological fertilizer for B cells. In the presence of BAFF and APRIL B cells are more likely to survive, proliferate and make antibodies.”
“Why are these studies important? It provides a rationale for targeting these factors and switching off the B cell response in MS. Despite this a drug called atacicept, that neutralises these agents, failed in MSers; the trial had to be stopped because atacicept increased MS disease activity. It is clear that the immunology of MS is much more complicated than we realise and it is not as simple as switching off molecule X and cell Y and hey presto we have a treatment that works. What is important is the B-cell; drugs that target B cells seem to be the very effective in MS! Mitoxantrone, natalizumab, fingolimod, rituximab, ocrelizumab and alemetuzumab, all have some anti-B cell activity. Why this interests me is that B-cells are where the EBV virus sets-up home in the body; therefore any drug that targets B-cells may be affecting EBV biology.”

“EBV reminds of Hotel California; once it checks-in it never leaves.”

“We are aware that some of you find these post on immunological research complicated. Do you think we should continue posting them?”

Other posts of interest:


ECTRIMS 2011: B cell targeting can trigger relapses
08 Nov 2011
L. Kappos, H-P. Hartung, M. S. Freedman, A. Boyko, D. Mikol, U. Freudensprung, T. Plitz for the ATAMS study group ATAMS: a randomised trial of the B-cell-targeting agent atacicept in patients with relapsing multiple sclerosis.

Multiple Sclerosis Research: Research: B cells Abit late Now
29 Mar 2012
It has already been shown that rituximab and ocreluzimab (B cell blocking agents) can inhibit some aspects of MS whilst Atacicept another B cell blocking agent makes MS worse. My old Boss (John Leslie Turk) reported on B …

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

9 comments

  • "Do you think we should continue posting them?"

    Yes please! Noone is forced to read everything.

  • Yes, please continue to post them.
    It gives me hope that things are being analysed
    and it is educational as well.

  • Yes, please continue posting using your format of "objective, method, results, conclusion." No one is forced to read anything, indeed.

  • Yes, do keep posting them – I have bought some immunology texts and refer to them when I don't understand. It's an education, I enjoy the learning.

  • Yes please keep posting. The immunological research papers are the ones I find most interesting. I often use your posts to look up the articles on PubMed and print them out at work. It has opened a whole universe of reading for me about this disease that plagues me!

  • Please continue if you have the time. Though I'm one of those who find these posts complicated and usually read only the conclusions etc

  • Please continue with these research posting, MouseDoctor. I have a few immunology books in my possession, so I can at least catch the gist of what these studies are saying. And anything I don't clearly understand, I can always ask my neuro.

  • "…fingolimod… all have some anti-B cell activity."

    I have been wondering… To my knowledge fingolimod targets t-cells, keeping them in the lymph nodes. I haven't heard of any effect on b-cells. Would be curious to learn about the anti-B cell acitivitiy in Fingolimod.

  • Re: Fingolimod and B cells.

    There is little doubt that fingolimod traps B cells as well. The following publication from 1999 discusses it in detail.

    Quesniaux et al. A novel immunosuppressant, FTY720, induces peripheral lymphodepletion of both T- and B cells and immunosuppression in baboons. Transpl Immunol. 1999 Sep;7(3):149-57.

    http://www.ncbi.nlm.nih.gov/pubmed/10608298

By Prof G

Translate

Categories

Recent Posts

Recent Comments

Archives