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Int. J. Mol. Sci. 2016, 17(9), 1407; doi:10.3390/ijms17091407

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

1
Hans-Berger Department of Neurology, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany
2
Integrated Research and Treatment Center—Center for Sepsis Control and Care (CSCC), Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany
3
Department of Neurology, University Hospital Würzburg, Josef-Schneider-Straße 11, 97080 Würzburg, Germany
4
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)
View Full-Text   |   Download PDF [1750 KB, uploaded 26 August 2016]   |  

Abstract

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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MDPI and ACS Style

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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