Natural killers cells and the action of daclizumab

Have we found a handle on the viral cause of MS? #MSBlog #MSResearch

“As most of you are aware of my pent up excitement about daclizumab as a treatment for RRMS. I have several reasons for taking this position. Firstly, it is a highly effective treatment that is superior to interferon-beta and has an impact on end-organ damage, i.e. it is one of an emerging group of high-efficacy therapies that reduces brain volume loss or brain atrophy. However, I am most excited by daclizumab as it seems to be an outlier when it comes to its mode of action. All the other high-efficacy therapies have in common some effect on the B-cell (natalizumab, fingolimod, alemtuzumab, mitoxantrone, anti-CD20 & HSCT/BMT). In comparison, daclizumab appears to leave the B-cell compartment intact and its efficacy is linked, at least in part, to expansion of natural killer cells (NK-cells) that express a molecule on their surface called CD56. What is the function of NK cells? They are part of the innate immune system and are anti-viral and part of the immune surveillance system for malignancies. Could the NK-cell be a one of the clues that MS is due to a virus? Personally, I think yes which is why I always include daclizumab on my storyboard when I discuss the hypothesis that MS is due to a virus. What are we doing about this? We as a group have therefore launched the Charcot Project, which is a group of projects that are looking into the viral hypothesis of MS.”

“The study below confirms that the expansion of the NK cell population is linked to the effectiveness of daclizumab. However, in the group of MSers with the lowest level of expansion of the NK-cells daclizumab is still effective, albeit at a lower level.”

“Daclizumab also challenges the immunological dogma that MS is an autoimmune disease. A large number of immunologists have claimed that MS is due to a problem with T-reg cells. Daclizumab actually reduces the number of T-regs in the peripheral blood. The reduction in T-reg numbers may explain why some daclizumab-treated MSers get other autoimmune diseases (skin, liver and gut) as a complication of daclizumab-treatment. What daclizumab maybe telling us is that MS is not an autoimmune disease? Interestingly, Professor David Hafler in his ACTRIMS-ECTRIMS lecture made the claim that we have now proven that MS is an autoimmune disease did not mention, or discuss daclizumab, once in his lecture.”

‘The great tragedy of Science — the slaying of a beautiful hypothesis by an ugly fact’. Thomas Henry Huxley (4 May, 1825 – 29 June 1895) 

“Is daclizumab a black swan?”

Elkins et al. CD56(bright) natural killer cells and response to daclizumab HYP in relapsing-remitting MS. Neurol Neuroimmunol Neuroinflamm. 2015 Jan 22;2(2):e65. doi: 10.1212/NXI.0000000000000065.

OBJECTIVE: To assess the relationship between CD56(bright) natural killer (NK) cells and MS disease activity in RRMSers treated with daclizumab high-yield process (DAC HYP).

METHODS: Data were from MSers enrolled in a 52-week randomized, double-blind, placebo-controlled study of DAC HYP and its extension study. Assessments included relationships of CD56(bright) NK cell numbers (identified using fluorescence-activated cell sorting) at weeks 4 and 8 with the numbers of new or newly enlarging T2-hyperintense lesions between weeks 24 and 52 and the annualized relapse rate.

RESULTS: In DAC HYP-treated MSers but not placebo-treated MSers, the numbers of CD56(bright) NK cells increased over 52 weeks of treatment, and their numbers at weeks 4 and 8 predicted the number of new or newly enlarging T2-hyperintense lesions between weeks 24 and 52 of treatment (p ≤ 0.005 for each comparison). Similar but non-significant trends were observed between CD56(bright) NK cell counts and the annualized relapse rate in DAC HYP-treated MSers. DAC HYP-treated MSers who showed lower levels of expansion of CD56(bright) NK cells still developed fewer new or newly enlarging T2-hyperintense lesions than placebo-treated patients during the first year of treatment.

CONCLUSIONS: CD56(bright) NK cells appear to mediate some of the treatment-related effects of DAC HYP, but their numbers do not account for the full effect of DAC HYP on MS-related outcomes.

CoI: multiple, I am also a co-author on this paper

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.


  • I have mixed feelings. This blog does a great service and enables a unique conversation. But I don't want researchers to be too distracted by the demands of PR. Social Media is a form of communication. It is not the substance of what you do. The reports from Ectrims teach me a lot about this disease I live with. Please don't skip that part in favor of generic marketing and pr strategy. These tools are not that different just because they are online.

  • is this an excuse for a jolly? three of your team? why don't you present some actual science- something that will stop our disease.

    • Maybe I will, but maybe I can't afford to go to ECTRIMS and an invite may help me to get there. Attending meeting without backing has significant costs.

      You miss the point of science meetings it is about learning and meeting your peers. Most MS neuros will attend this annual meeting because this is where most of the clinical research on MS is presented.

      Neuros are terrible as using social media and some will say that is a good thing. I was a recent meeting where someone must have paid a bit of cash to develop an app that allowed the participants to ask questions. They could have done that using twitter for nothing.

  • On the subject of webinars…. Today is the Progressive MS webinar by MSIF Multiple Sclerosis International Federation 5.30pm to 6.30pm GMT.
    With research scientists, Professor Alan Thompson and Dr Olga Ciccarelli and two MSIF presenters. Open to anyone who would be interested.
    To register for webinar or to watch later here's the weblink.

  • This is quite tantalising. Can I ask, if it did prove to be ebv-mediated, what would be the best way to treat it as an induction therapy? Is there a combo of drugs out there that can completely rid you of ebv?

  • The cyber-gremlins are having fun – why are several of the comments under this post dated 26 and 27 November 2014 when the posting itself is dated 5th February 2015???

  • Very interesting take on MS etiology.
    There are several pieces of evidence that suggest that multiple sclerosis is an "autoimmune paradox".
    Arguments for MS=autoimmunity.
    1. HLA genetics
    2. Several immune genes including IL-12, IL-7R and others as risk factors
    3. Presence of anti-myelin IgG in CSF.
    4. Presence of immune cells and cytokines in MS lesions.
    5. Blocking immune cell trafficking to the CNS with tysabri is the most efficacious therapy for MS

    Arguments against MS as an autoimmune disease:
    1. Type I IFN, which includes IFN-beta, drives pathology in lupus, sjogrens, NMO and others. But recombinant IFNs are an effective (somewhat) treatment for RRMS.
    2. anti-TNF therapies increases relapse rates in RRMS. This is the blockbuster drug for RA, psoriatic arthritis, ankylosing, etc…
    3. Blockade of BAFF/Blys (B-cell cytokines) worsened RRMS but Benlysta (anti-BAFF) is the first approved drug in lupus.
    4. There is data suggesting that an MS risk allele in CD40 decreases expression of this receptor. In RA, there is also a risk allele in CD40 but this increases receptor expression.
    The interesting thing about the arguments against "MS as an autoimmunity" is that molecules in the TNF superfamily (TNF, BAFF, CD40) have the opposite effects in MS compared to other autoimmune diseases. One could speculate that this is because EBV is the/a culprit in MS pathology but there is also an EBV hypothesis/association reported in lupus. Much more research is needed…

By Prof G



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