title: Efficacy of Polyvalent Human Immunoglobulins in an Animal Model of Neuromyelitis Optica Evoked by Intrathecal Anti-Aquaporin 4 Antibodies.
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.
authors: Hans-Berger Department of Neurology, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany. benedikt.gruenewald@med.uni-jena.de.|Integrated Research and Treatment Center-Center for Sepsis Control and Care (CSCC), Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany. benedikt.gruenewald@med.uni-jena.de.|Department of Neurology, University Hospital Würzburg, Josef-Schneider-Straße 11, 97080 Würzburg, Germany. benedikt.gruenewald@med.uni-jena.de.
authors: Benedikt
authors: B
authors: Grünewald
authors: Departments of Neurology and Ophthalmology, University of Colorado Denver, Aurora, CO 80045, USA. Jeffrey.Bennett@ucdenver.edu.
authors: Jeffrey L
authors: JL
authors: Bennett
authors: Department of Neurology, University Hospital Würzburg, Josef-Schneider-Straße 11, 97080 Würzburg, Germany. kv.toyka@uni-wuerzburg.de.
authors: Klaus V
authors: KV
authors: Toyka
authors: Department of Neurology, University Hospital Würzburg, Josef-Schneider-Straße 11, 97080 Würzburg, Germany. sommer@uni-wuerzburg.de.
authors: Claudia
authors: C
authors: Sommer
authors: Hans-Berger Department of Neurology, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany. christian.geis@med.uni-jena.de.|Integrated Research and Treatment Center-Center for Sepsis Control and Care (CSCC), Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany. christian.geis@med.uni-jena.de.|Department of Neurology, University Hospital Würzburg, Josef-Schneider-Straße 11, 97080 Würzburg, Germany. christian.geis@med.uni-jena.de.
authors: Christian
authors: C
authors: Geis
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000276:immunology* / Q000378:metabolism; D001323:Autoantibodies / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D004195:Disease Models, Animal; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007278:Injections, Spinal; D009471:Neuromyelitis Optica / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D051381:Rats
chemical_list: D051401:Aquaporin 4; D001323:Autoantibodies; D007074:Immunoglobulin G
keywords: IVIg; NMOSD; aquaporin 4; autoantibody; intrathecal application