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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2011

Open Access 01-12-2011 | Research

Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders

Authors: Simone Mader, Viktoria Gredler, Kathrin Schanda, Kevin Rostasy, Irena Dujmovic, Kristian Pfaller, Andreas Lutterotti, Sven Jarius, Franziska Di Pauli, Bettina Kuenz, Rainer Ehling, Harald Hegen, Florian Deisenhammer, Fahmy Aboul-Enein, Maria K Storch, Peter Koson, Jelena Drulovic, Wolfgang Kristoferitsch, Thomas Berger, Markus Reindl

Published in: Journal of Neuroinflammation | Issue 1/2011

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Abstract

Background

Serum autoantibodies against the water channel aquaporin-4 (AQP4) are important diagnostic biomarkers and pathogenic factors for neuromyelitis optica (NMO). However, AQP4-IgG are absent in 5-40% of all NMO patients and the target of the autoimmune response in these patients is unknown. Since recent studies indicate that autoimmune responses to myelin oligodendrocyte glycoprotein (MOG) can induce an NMO-like disease in experimental animal models, we speculate that MOG might be an autoantigen in AQP4-IgG seronegative NMO. Although high-titer autoantibodies to human native MOG were mainly detected in a subgroup of pediatric acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS) patients, their role in NMO and High-risk NMO (HR-NMO; recurrent optic neuritis-rON or longitudinally extensive transverse myelitis-LETM) remains unresolved.

Results

We analyzed patients with definite NMO (n = 45), HR-NMO (n = 53), ADEM (n = 33), clinically isolated syndromes presenting with myelitis or optic neuritis (CIS, n = 32), MS (n = 71) and controls (n = 101; 24 other neurological diseases-OND, 27 systemic lupus erythematosus-SLE and 50 healthy subjects) for serum IgG to MOG and AQP4. Furthermore, we investigated whether these antibodies can mediate complement dependent cytotoxicity (CDC). AQP4-IgG was found in patients with NMO (n = 43, 96%), HR-NMO (n = 32, 60%) and in one CIS patient (3%), but was absent in ADEM, MS and controls. High-titer MOG-IgG was found in patients with ADEM (n = 14, 42%), NMO (n = 3, 7%), HR-NMO (n = 7, 13%, 5 rON and 2 LETM), CIS (n = 2, 6%), MS (n = 2, 3%) and controls (n = 3, 3%, two SLE and one OND). Two of the three MOG-IgG positive NMO patients and all seven MOG-IgG positive HR-NMO patients were negative for AQP4-IgG. Thus, MOG-IgG were found in both AQP4-IgG seronegative NMO patients and seven of 21 (33%) AQP4-IgG negative HR-NMO patients. Antibodies to MOG and AQP4 were predominantly of the IgG1 subtype, and were able to mediate CDC at high-titer levels.

Conclusions

We could show for the first time that a subset of AQP4-IgG seronegative patients with NMO and HR-NMO exhibit a MOG-IgG mediated immune response, whereas MOG is not a target antigen in cases with an AQP4-directed humoral immune response.
Appendix
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Metadata
Title
Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders
Authors
Simone Mader
Viktoria Gredler
Kathrin Schanda
Kevin Rostasy
Irena Dujmovic
Kristian Pfaller
Andreas Lutterotti
Sven Jarius
Franziska Di Pauli
Bettina Kuenz
Rainer Ehling
Harald Hegen
Florian Deisenhammer
Fahmy Aboul-Enein
Maria K Storch
Peter Koson
Jelena Drulovic
Wolfgang Kristoferitsch
Thomas Berger
Markus Reindl
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2011
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-8-184

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