Back to Search Start Over

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

Authors :
Benedikt Grünewald
Jeffrey L. Bennett
Klaus V. Toyka
Claudia Sommer
Christian Geis
Source :
International Journal of Molecular Sciences, Vol 17, Iss 9, p 1407 (2016)
Publication Year :
2016
Publisher :
MDPI AG, 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.

Details

Language :
English
ISSN :
14220067
Volume :
17
Issue :
9
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.488f4491cfc34e5ba20a9027369f5c18
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms17091407