B Cell, Th17, and Neutrophil Related Cerebrospinal Fluid Cytokine/Chemokines Are Elevated in MOG Antibody Associated Demyelination
February
B Cell, Th17, and Neutrophil Related Cerebrospinal Fluid Cytokine/Chemokines Are Elevated in MOG Antibody Associated Demyelination
Editor: Edgar Meinl 0 1
LMU Munich 0 1
GERMANY 0 1
Kavitha Kothur 0 1
Louise Wienholt 0 1
Esther M Tantsis 0 1
John Earl 0 1
Sushil Bandodkar 0 1
Kristina Prelog 0 1
Fiona Tea 0 1
Sudarshini Ramanathan 0 1
Fabienne Brilot 0 1
Russell C. Dale 0 1
0 1 Neuroimmunology group, Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead, University of Sydney , Sydney, NSW , Australia , 2 Department of Clinical Immunology, Royal Prince Alfred Hospital , Sydney, NSW , Australia , 3 Department of Biochemistry, The Children's Hospital at Westmead , Sydney, NSW , Australia , 4 Department of Medical Imaging, The Children's Hospital at Westmead , Sydney, NSW , Australia
1 Abbreviations: MOG , Myelin oligodendrocyte glycoprotein antibody; ADEM, Acute Disseminated
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Data Availability Statement: All relevant data are
within the paper and its Supporting Information file.
Funding: This work was supported by a scholarship
from the Petre Foundation, an Australian
Postgraduate award, and Multiple Sclerosis Research
Australia. The funders had no role in study design,
data collection and analysis, decision to publish, or
preparation of the manuscript.
Competing Interests: The authors have declared
that no competing interests exist.
Background Aim
Methods
Results
Myelin oligodendrocyte glycoprotein antibody (MOG Ab) associated demyelination
represents a subgroup of autoimmune demyelination that is separate from multiple sclerosis and
aquaporin 4 IgG-positive NMO, and can have a relapsing course. Unlike NMO and MS,
there is a paucity of literature on immunopathology and CSF cytokine/chemokines in MOG
Ab associated demyelination.
To study the differences in immunopathogenesis based on cytokine/chemokine profile in
MOG Ab-positive (POS) and -negative (NEG) groups.
We measured 34 cytokines/chemokines using multiplex immunoassay in CSF collected
from paediatric patients with serum MOG Ab POS [acute disseminated encephalomyelitis
(ADEM = 8), transverse myelitis (TM = 2) n = 10] and serum MOG Ab NEG (ADEM = 5, TM
= 4, n = 9) demyelination. We generated normative data using CSF from 20
non-inflammatory neurological controls.
The CSF cytokine and chemokine levels were higher in both MOG Ab POS and MOG Ab
NEG demyelination groups compared to controls. The CSF in MOG Ab POS patients
showed predominant elevation of B cell related cytokines/chemokines (CXCL13, APRIL,
BAFF and CCL19) as well as some of Th17 related cytokines (IL-6 AND G-CSF) compared
Encephalomyelitis; TM, Transverse Myelitis; NMO,
Neuromyelitis Optica; NMOSD, Neuromyelitis Optica
Spectrum Disorders; MRI, Magnetic Resonance
Imaging; CSF, Cerebrospinal Fluid; Ab, Antibody;
POS, Positive; NEG, Negative; EAE, Experimental
Allergic Encephalomyelitis.
to MOG Ab NEG group (all p<0.01). In addition, patients with elevated CSF MOG antibodies
had higher CSF CXCL13, CXCL12, CCL19, IL-17A and G-CSF than patients without CSF
MOG antibodies.
Conclusion
Our findings suggest that MOG Ab POS patients have a more pronounced CNS
inflammatory response with elevation of predominant humoral associated cytokines/chemokines, as
well as some Th 17 and neutrophil related cytokines/chemokines suggesting a differential
inflammatory pathogenesis associated with MOG antibody seropositivity. This cytokine/
chemokine profiling provides new insight into disease pathogenesis, and improves our
ability to monitor inflammation and response to treatment. In addition, some of these molecules
may represent potential immunomodulatory targets.
Introduction
Myelin oligodendrocyte glycoprotein (MOG) is a myelin antigen located at the outer surface of
the central nervous system (CNS) myelin sheath, and is a target for autoimmune responses
that results in CNS inflammation and demyelination [
1
]. Using cell-based assays, serum MOG
antibody has been shown to be primarily associated with pediatric acute disseminated
encephalomyelitis (ADEM), optic neuritis (ON), transverse myelitis (TM), and aquaporin 4
antibodynegative neuromyelitis optica (NMO) [
2–4
]. In adults, MOG antibody is predominantly seen
in association with NMO/NMOSD, including bilateral and/or recurrent optic neuritis, and
transverse myelitis, but rarely seen in patients with MS [
5–8
]. While some studies evaluating
paediatric patients showed a persistence of MOG antibody seropositivity with relapsing
disease, the role of MOG antibody as a biomarker for disease recurrence or severity remains to be
clarified [
9, 10
]. Relapsing MOG Ab demyelination syndromes are considered distinct from
multiple sclerosis (MS) based on clinical and neuroimaging features, and MOG antibody
seropositivity is associated with a non-MS course at 1-year follow-up [
11, 12
].
There is emerging evidence that MOG antibodies are pathogenic in human demyelinating
diseases. In vitro experiments have (...truncated)