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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

Open access
in cooperation with the Neuromyelitis Optica Study Group (NEMOS), Jarius, Sven, Ruprecht, Klemens, Kleiter, Ingo, Borisow, Nadja, Asgari, Nasrin, Pitarokoili, Kalliopi, Pache, Florence, Stich, Oliver, Beume, Lena-Alexandra, Hümmert, Martin W., Trebst, Corinna, Ringelstein, Marius, Aktas, Orhan, Winkelmann, Alexander, Buttmann, Mathias, Schwarz, Alexander, Zimmermann, Hanna, Brandt, Alexander U., Franciotta, Diego, Capobianco, Marco, Kuchling, Joseph, Haas, Jürgen, Korporal-Kuhnke, Mirjam, Lillevang, Soeren Thue, Fechner, Kai, Schanda, Kathrin, Paul, Friedemann, Wildemann, Brigitte, Reindl, Markus·2016·Journal of Neuroinflammation
DOI 10.1186/s12974-016-0717-1
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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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Authors
in cooperation with the Neuromyelitis Optica Study Group (NEMOS), Jarius, S., Ruprecht, K., Kleiter, I., Borisow, N., Asgari, N., Pitarokoili, K., Pache, F., Stich, O., Beume, L.-A., Hümmert, M. W., Trebst, C., Ringelstein, M., Aktas, O., Winkelmann, A., Buttmann, M., Schwarz, A., Zimmermann, H., Brandt, A. U., Franciotta, D., Capobianco, M., Kuchling, J., Haas, J., Korporal-Kuhnke, M., Lillevang, S. T., Fechner, K., Schanda, K., Paul, F., Wildemann, B., & Reindl, M.
Venue
Journal of Neuroinflammation
Publisher
Springer Science and Business Media LLC
Published
2016-10-27
Volume
13
Issue
1
Pages
279-279
ISSN
1742-2094 (ISSN-L)
DOI
10.1186/s12974-016-0717-1
OpenAlex
W2545267953
Cited by
429
References
68
FWCI
43.26
Type
journal article
Language
en
Open access
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in cooperation with the Neuromyelitis Optica Study Group (NEMOS), Jarius, S., Ruprecht, K., Kleiter, I., Borisow, N., Asgari, N., Pitarokoili, K., Pache, F., Stich, O., Beume, L.-A., Hümmert, M. W., Trebst, C., Ringelstein, M., Aktas, O., Winkelmann, A., Buttmann, M., Schwarz, A., Zimmermann, H., Brandt, A. U., . . . Reindl, M. (2016). 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. Journal of Neuroinflammation. https://doi.org/10.1186/s12974-016-0717-1

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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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