Thursday, 23 March 2017

Natural Killer cells and MS

Natural killer cell subpopulations are associated with MRI activity in a relapsing-remitting multiple sclerosis patient cohort from Australia.Caruana P, Lemmert K, Ribbons K, Lea R, Lechner-Scott J. Mult Scler. 2016:1352458516679267. doi: 10.1177/1352458516679267

To examine NK subsets in MS patients on different treatments and to evaluate the role of NK subsets as indicators for disease activity.


METHODS: We measured NK subset levels in blood obtained from 110 relapsing-remitting MS patients. Patients were either off treatment or on treatment with natalizumab, fingolimod, glatiramer acetate or beta-interferon. Disease activity was defined according to 'No Evidence of Disease Activity' (NEDA) criteria within an observation period of up to 2.4 years. The mean NK subset levels were compared among treatment groups using multivariate analysis of variance (ANOVA) and association analysis with disease activity performed using multi-factor logistic regression.


RESULTS: Our analysis revealed differences in NK cells and subsets on treatment compared to off treatment ( p < 0.0005). A high proportion of bright NK cells were significantly associated with stable magnetic resonance imaging (MRI) imaging after adjusting for treatment effects ( p < 0.05).


CONCLUSION: The independent association of NK subsets with MRI stability needs to be confirmed in prospective studies to test their usefulness in predicting disease activity in MS patients.



So a suggestion that NKbright cells that are expanded by daclizumab in this study they suggest high levels are associated with stable disease...Is this a sign that its not B cells?

5 comments:

  1. That NK cells look wicked :-)
    But NK cells go up on rituximab, so maybe it it some balance thing between disappearing B-cells and NKs upregulating? My hand is still on the B-cell button :-)

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  2. Natural killer cells
    Natural killer cells (NK cells) are large granular lymphocytes, important in
    the defense against intracellular infections and tumors. In contrast to B and T
    lymphocyte receptors, NK cell receptors do not undergo somatic
    rearrangement, enabling NK cells to mediate host defenses without any prior
    sensitization by antigen.81 NK cells are important inhibitors of inflammation
    in MS. They were thought to exert their suppressive function through
    secretion of cytokines, but in the clinical trials with the anti-CD25 antibody
    daclizumab it was discovered that daclizumab expanded the CD56high
    subset of NK cells by up to 500 %.82 It has thereafter been demonstrated that
    this cell population can act as a regulatory NK cell population, exerting its
    action by killing activated autologous T cells.82 This supports the notion that
    NK cells exert their suppressive function through cell-to-cell interactions. It
    has also been shown that NK cells must be present in the CNS to regulate the
    development of autoimmune responses in EAE. The CX3CL1 (fractalkine)
    receptor is critical for CNS NK cell recruitment, but not for B or T cells.
    CX3CL1 knockout mice have fewer NK cells infiltrating the CNS, but
    normal numbers in the periphery and develop more severe EAE. Joachim burman

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    Replies
    1. Thanks for this. I am aware that daclizumab increases this subpopulation but is this how it works. It will block T cell proliferation and it will block memory B cell activity which both express CD25.

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  3. This as allready been proved
    http://www.pnas.org/content/103/15/5941

    What new about it?

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    Replies
    1. please see above where is the proof that this is how it works

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