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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2016

Open Access 01-12-2016 | Research

MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin

Authors: Sven Jarius, Klemens Ruprecht, Ingo Kleiter, Nadja Borisow, Nasrin Asgari, Kalliopi Pitarokoili, Florence Pache, Oliver Stich, Lena-Alexandra Beume, Martin W. Hümmert, Corinna Trebst, Marius Ringelstein, Orhan Aktas, Alexander Winkelmann, Mathias Buttmann, Alexander Schwarz, Hanna Zimmermann, Alexander U. Brandt, Diego Franciotta, Marco Capobianco, Joseph Kuchling, Jürgen Haas, Mirjam Korporal-Kuhnke, Soeren Thue Lillevang, Kai Fechner, Kathrin Schanda, Friedemann Paul, Brigitte Wildemann, Markus Reindl, in cooperation with the Neuromyelitis Optica Study Group (NEMOS)

Published in: Journal of Neuroinflammation | Issue 1/2016

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Abstract

Background

Antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) have been suggested to play a role in a subset of patients with neuromyelitis optica and related disorders.

Objective

To assess (i) the frequency of MOG-IgG in a large and predominantly Caucasian cohort of patients with optic neuritis (ON) and/or myelitis; (ii) the frequency of MOG-IgG among AQP4-IgG-positive patients and vice versa; (iii) the origin and frequency of MOG-IgG in the cerebrospinal fluid (CSF); (iv) the presence of MOG-IgG at disease onset; and (v) the influence of disease activity and treatment status on MOG-IgG titers.

Methods

614 serum samples from patients with ON and/or myelitis and from controls, including 92 follow-up samples from 55 subjects, and 18 CSF samples were tested for MOG-IgG using a live cell-based assay (CBA) employing full-length human MOG-transfected HEK293A cells.

Results

MOG-IgG was detected in 95 sera from 50 patients with ON and/or myelitis, including 22/54 (40.7%) patients with a history of both ON and myelitis, 22/103 (21.4%) with a history of ON but no myelitis and 6/45 (13.3%) with a history of longitudinally extensive transverse myelitis but no ON, and in 1 control patient with encephalitis and a connective tissue disorder, all of whom were negative for AQP4-IgG. MOG-IgG was absent in 221 further controls, including 83 patients with AQP4-IgG-seropositive neuromyelitis optica spectrum disorders and 85 with multiple sclerosis (MS). MOG-IgG was found in 12/18 (67%) CSF samples from MOG-IgG-seropositive patients; the MOG-IgG-specific antibody index was negative in all cases, indicating a predominantly peripheral origin of CSF MOG-IgG. Serum and CSF MOG-IgG belonged to the complement-activating IgG1 subclass. MOG-IgG was present already at disease onset. The antibodies remained detectable in 40/45 (89%) follow-up samples obtained over a median period of 16.5 months (range 0–123). Serum titers were higher during attacks than during remission (p < 0.0001), highest during attacks of simultaneous myelitis and ON, lowest during acute isolated ON, and declined following treatment.

Conclusions

To date, this is the largest cohort studied for IgG to human full-length MOG by means of an up-to-date CBA. MOG-IgG is present in a substantial subset of patients with ON and/or myelitis, but not in classical MS. Co-existence of MOG-IgG and AQP4-IgG is highly uncommon. CSF MOG-IgG is of extrathecal origin. Serum MOG-IgG is present already at disease onset and remains detectable in the long-term course. Serum titers depend on disease activity and treatment status.
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Metadata
Title
MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin
Authors
Sven Jarius
Klemens Ruprecht
Ingo Kleiter
Nadja Borisow
Nasrin Asgari
Kalliopi Pitarokoili
Florence Pache
Oliver Stich
Lena-Alexandra Beume
Martin W. Hümmert
Corinna Trebst
Marius Ringelstein
Orhan Aktas
Alexander Winkelmann
Mathias Buttmann
Alexander Schwarz
Hanna Zimmermann
Alexander U. Brandt
Diego Franciotta
Marco Capobianco
Joseph Kuchling
Jürgen Haas
Mirjam Korporal-Kuhnke
Soeren Thue Lillevang
Kai Fechner
Kathrin Schanda
Friedemann Paul
Brigitte Wildemann
Markus Reindl
in cooperation with the Neuromyelitis Optica Study Group (NEMOS)
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2016
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-016-0717-1

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