Anti-MOG antibodies are present in a subgroup of patients with a neuromyelitis optica phenotype
Prbstel et al. Journal of Neuroinflammation
Anti-MOG antibodies are present in a subgroup of patients with a neuromyelitis optica phenotype
Anne-Katrin Prbstel 1 3
Gabrielle Rudolf 0 2
Klaus Dornmair 4
Nicolas Collongues 0 2
Jean-Baptiste Chanson 0 2
Nicholas SR Sanderson 1 3
Raija LP Lindberg 1 3
Ludwig Kappos 1 3
Jrme de Seze 0 2
Tobias Derfuss 1 3
0 Department of Neurology, Hopital de Hautepierre, University Hospital Strasbourg , 1 Avenue Moliere, 67100 Strasbourg , France
1 Department of Neurology, University Hospital Basel , Petersgraben 4, 4031 Basel , Switzerland
2 Department of Neurology, Hopital de Hautepierre, University Hospital Strasbourg , 1 Avenue Moliere, 67100 Strasbourg , France
3 Department of Biomedicine, University of Basel , Hebelstrasse 20, 4031 Basel , Switzerland
4 Institute of Clinical Neuroimmunology, University Hospital Grosshadern , Max-Lebsche-Platz 31, 81377 Munich , Germany
Background: Antibodies against myelin oligodendrocyte glycoprotein (MOG) have been identified in a subgroup of pediatric patients with inflammatory demyelinating disease of the central nervous system (CNS) and in some patients with neuromyelitis optica spectrum disorder (NMOSD). The aim of this study was to examine the frequency, clinical features, and long-term disease course of patients with anti-MOG antibodies in a European cohort of NMO/NMOSD. Findings: Sera from 48 patients with NMO/NMOSD and 48 patients with relapsing-remitting multiple sclerosis (RR-MS) were tested for anti-aquaporin-4 (AQP4) and anti-MOG antibodies with a cell-based assay. Anti-MOG antibodies were found in 4/17 patients with AQP4-seronegative NMO/NMOSD, but in none of the AQP4-seropositive NMO/NMOSD (n = 31) or RR-MS patients (n = 48). MOG-seropositive patients tended towards younger disease onset with a higher percentage of patients with pediatric (<18 years) disease onset (MOG+, AQP4+, MOG/AQP4: 2/4, 3/31, 0/13). MOG-seropositive patients presented more often with positive oligoclonal bands (OCBs) (3/3, 5/29, 1/13) and brain magnetic resonance imaging (MRI) lesions during disease course (2/4, 5/31, 1/13). Notably, the mean time to the second attack affecting a different CNS region was longer in the anti-MOG antibody-positive group (11.3, 3.2, 3.4 years). Conclusions: MOG-seropositive patients show a diverse clinical phenotype with clinical features resembling both NMO (attacks mainly confined to the spinal cord and optic nerves) and MS with an opticospinal presentation (positive OCBs, brain lesions). Anti-MOG antibodies can serve as a diagnostic and maybe prognostic tool in patients with an AQP4-seronegative NMO phenotype and should be tested in those patients.
Neuromyelitis optica; Neuromyelitis optica spectrum disorder; Anti-aquaporin-4 antibodies; Anti-MOG antibodies; Inflammatory demyelinating CNS disease
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Findings
Introduction
Neuromyelitis optica (NMO) is a clinically defined entity
within the spectrum of inflammatory demyelinating diseases
of the central nervous system (CNS) which is characterized
by inflammatory attacks that are confined to the spinal cord
and the optic nerves [1,2]. Limited forms of the disease are
considered as NMO spectrum disorder (NMOSD) [3]. The
finding of anti-aquaporin-4 (AQP4) antibodies in the
majority of patients with NMO [4] and some patients with
NMOSD has advanced our pathogenic understanding of the
disease [5] and has directed the therapeutic approach
towards a B cell-directed therapy [6]. However, 10% to 50%
of NMO patients, depending on cohorts and assays used,
are AQP4-negative [7]. Recent evidence suggests that some
of the NMO cases are related to antibodies against myelin
oligodendrocyte glycoprotein (MOG) [8-17].
Previously, we showed that anti-MOG antibodies are
present in about 25% of pediatric patients with a first
episode of acute demyelination and that these antibodies
correlate with the disease course [18,19]. The aims of the present
study were a) to analyze the presence of anti-MOG
antibodies in an independent blinded cohort of patients with
NMO/NMOSD and multiple sclerosis (MS) using the
previously described cell-based assay (CBA) [18], b) to correlate
antibody findings to clinical and magnetic resonance
imaging (MRI) parameters of MOG-seropositive and
AQP4seropositive NMO patients and NMO patients with no
detectable antibodies, and c) to characterize the long-term
clinical outcome of the MOG-seropositive patients.
Methods
A total of 135 patients including patients with NMO/
NMOSD (n = 48), relapsing-remitting MS (n = 48), and
healthy donors (n = 39) were analyzed. NMO/NMOSD and
MS patient samples were collected at the University
Hospital, Strasbourg, France between 2006 and 2012. The
clinical data were obtained retrospectively from the European
Database for Multiple Sclerosis (EDMUS). Healthy donor
samples were obtained from the blood donation center,
Etablissement Franais du Sang (EFS), Strasbourg, France.
Diagnoses of NMO/NMOSD or MS were based on the
revised Wing (...truncated)