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

• Published in: International journal of molecular sciences Vol. 17; no. 9; p. 1407
• Main Authors: Grünewald, Benedikt, Bennett, Jeffrey L, Toyka, Klaus V, Sommer, Claudia, Geis, Christian
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 26.08.2016; MDPI AG
• Subjects: Animals; aquaporin 4; Aquaporin 4 - immunology; Aquaporin 4 - metabolism; Autoantibodies - administration & dosage; Autoantibodies - immunology; Autoantibodies - therapeutic use; autoantibody; Disease Models, Animal; Humans; Immunoglobulin G - immunology; Injections, Spinal; intrathecal application; IVIg; Neuromyelitis Optica - drug therapy; Neuromyelitis Optica - immunology; Neuromyelitis Optica - metabolism; NMOSD; Rats; IVIg; intrathecal application; autoantibody; NMOSD; aquaporin 4
• ISSN: 1422-0067; 1422-0067
• DOI: 10.3390/ijms17091407

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.