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Int. J. Mol. Sci. 2016, 17(9), 1407;

Efficacy of Polyvalent Human Immunoglobulins in an Animal Model of Neuromyelitis Optica Evoked by Intrathecal Anti-Aquaporin 4 Antibodies

Hans-Berger Department of Neurology, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany
Integrated Research and Treatment Center—Center for Sepsis Control and Care (CSCC), Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany
Department of Neurology, University Hospital Würzburg, Josef-Schneider-Straße 11, 97080 Würzburg, Germany
Departments of Neurology and Ophthalmology, University of Colorado Denver, Aurora, CO 80045, USA
Author to whom correspondence should be addressed.
Academic Editor: Irmgard Tegeder
Received: 10 June 2016 / Revised: 16 August 2016 / Accepted: 19 August 2016 / Published: 26 August 2016
(This article belongs to the Special Issue Aquaporin)
PDF [1750 KB, uploaded 26 August 2016]


Neuromyelitis Optica Spectrum Disorders (NMOSD) are associated with autoantibodies (ABs) targeting the astrocytic aquaporin-4 water channels (AQP4-ABs). These ABs have a direct pathogenic role by initiating a variety of immunological and inflammatory processes in the course of disease. In a recently-established animal model, chronic intrathecal passive-transfer of immunoglobulin G from NMOSD patients (NMO-IgG), or of recombinant human AQP4-ABs (rAB-AQP4), provided evidence for complementary and immune-cell independent effects of AQP4-ABs. Utilizing this animal model, we here tested the effects of systemically and intrathecally applied pooled human immunoglobulins (IVIg) using a preventive and a therapeutic paradigm. In NMO-IgG animals, prophylactic application of systemic IVIg led to a reduced median disease score of 2.4 on a 0–10 scale, in comparison to 4.1 with sham treatment. Therapeutic IVIg, applied systemically after the 10th intrathecal NMO-IgG injection, significantly reduced the disease score by 0.8. Intrathecal IVIg application induced a beneficial effect in animals with NMO-IgG (median score IVIg 1.6 vs. sham 3.7) or with rAB-AQP4 (median score IVIg 2.0 vs. sham 3.7). We here provide evidence that treatment with IVIg ameliorates disease symptoms in this passive-transfer model, in analogy to former studies investigating passive-transfer animal models of other antibody-mediated disorders. View Full-Text
Keywords: NMOSD; aquaporin 4; autoantibody; IVIg; intrathecal application NMOSD; aquaporin 4; autoantibody; IVIg; intrathecal application

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Grünewald, B.; Bennett, J.L.; Toyka, K.V.; Sommer, C.; Geis, C. Efficacy of Polyvalent Human Immunoglobulins in an Animal Model of Neuromyelitis Optica Evoked by Intrathecal Anti-Aquaporin 4 Antibodies. Int. J. Mol. Sci. 2016, 17, 1407.

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