Multiple Sclerosis Journal - October 2017 - 1479

679267
research-article2016

MSJ0010.1177/1352458516679267Multiple Sclerosis JournalP Caruana, K Lemmert

MULTIPLE
SCLEROSIS
JOURNAL

MSJ

Original Research Paper

Natural killer cell subpopulations are
associated with MRI activity in a relapsingremitting multiple sclerosis patient cohort
from Australia

Multiple Sclerosis Journal
2017, Vol. 23(11) 1479-1487
DOI: 10.1177/
https://doi.org/10.1177/1352458516679267
1352458516679267
https://doi.org/10.1177/1352458516679267
© The Author(s), 2016.
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P Caruana, K Lemmert, K Ribbons, R Lea and J Lechner-Scott

Abstract
Background: The importance of the innate immune system in multiple sclerosis (MS) is increasingly
recognized and the role of natural killer (NK) cells in controlling autoimmunity may be an important
modulator of disease activity.
Objective: 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.

Keywords: Lymphocytes, natural killer cells, CD56 bright, CD56 dim
Date received: 8 February 2016; revised: 15 September 2016; accepted: 15 October 2016

Introduction
In recent years, the role of the innate immune system
in multiple sclerosis (MS), in particular the role of
natural killer (NK) cells and their subsets, has gained
interest. A growing body of literature supports that
NK cells and their subsets may have a role of dampening autoimmunity for MS.1-4
NK cells represent up to 15% of the blood lymphocytes and are part of the innate immune system. NK
cells can be divided into bright and dim subsets
according to the expression of the surface molecule
CD56.5 The following distinction into CD56 dim and
bright is a simplification, as multiple further subsets

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can be distinguished when looking at intermediate
maturity forms or when using other receptors to discriminate NK cell subclasses.4,6,7

CD56 dim NK cells
CD56 dim NK cells are the predominant subset in
blood, making up 90% of the NK cell pool in the
periphery. They are believed to be the effector population, capable of direct lysis of infected or tumour cells
by multiple pathways. CD56 dim NK cells are more
granular, containing granzyme and perforin among
other substances to enable target cell lysis.5 CD56
dim also carry CD16 receptors. The latter recognizes

Correspondence to:
K Ribbons
Department of Neurology,
John Hunter Hospital,
Lookout Road, New
Lambton, NSW 2305,
Australia.
karen.ribbons@hnehealth.
nsw.gov.au
P Caruana J Lechner-Scott
Department of Neurology,
John Hunter Hospital, New
Lambton, NSW, Australia;
Hunter Medical Research
Institute, New Lambton,
NSW, Australia
K Lemmert
Pathology North, New
Lambton, NSW, Australia
K Ribbons
Department of Neurology,
John Hunter Hospital, New
Lambton, NSW, Australia
R Lea
Hunter Medical Research
Institute, New Lambton,
NSW, Australia

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