Efficacy of Polyvalent Human Immunoglobulins in an Animal Model of Neuromyelitis Optica Evoked by Intrathecal Anti-Aquaporin 4 Antibodies
Please always quote using this URN: urn:nbn:de:bvb:20-opus-166000
- 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.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.…
Author: | Benedikt Grünewald, Jeffrey L. Bennett, Klaus V. Toyka, Claudia Sommer, Christian Geis |
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URN: | urn:nbn:de:bvb:20-opus-166000 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Neurologische Klinik und Poliklinik |
Language: | English |
Parent Title (English): | International Journal of Molecular Sciences |
Year of Completion: | 2016 |
Volume: | 17 |
Issue: | 9 |
Pagenumber: | 1407 |
Source: | International Journal of Molecular Sciences 2016, 17, 1407; doi:10.3390/ijms17091407 |
DOI: | https://doi.org/10.3390/ijms17091407 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | IVIg; NMOSD; aquaporin 4; autoantibody; intrathecal application |
Release Date: | 2018/10/21 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |