Passive transfer of glycine receptor-antibody IgG induces anxiety-like behaviour in mice (P2.200)

OBJECTIVE: To determine the pathogenic effects of GlyR-Abs in vivo using an animal model. BACKGROUND: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare neurological disease that can be very severe and potentially fatal. PERM is characterized mainly by muscle rigidity, stimulus-sensitive spasms, myoclonus, hyperekplexia, autonomic instability plus brainstem dysfunction. An increasing number of PERM patients with antibodies to the glycine receptor (GlyR) have been reported, including a subset of patients who display anxiety behaviour. We previously showed that GlyR-Abs have pathogenic effects in vitro (Carvajal-Gonzalez et al 2014). However, the pathogenic role of GlyR-Abs in vivo have not been explored. DESIGN/METHODS: Twelve C57/BL6 mice received one intracerebroventricular (i.c.v) injection of PERM patient or healthy control IgG. 24 hrs after the injection locomotor performance (rotarod, narrow beam gait analysis, grip strength), anxiety (dark-light box) and open field activity were assessed blindly on days 1-3 and 5-7. Unblinding was performed after all analyses. RESULTS: PERM-IgG-injected mice did less crosses between the light and the dark compartment (p = 0.0182) and spent less time in the light compartment (p = 0.0428) compared to HC-IgG injected mice. In addition, analysis of the open field showed that GlyR-Ab injected mice showed a trend towards less entrances to the central squares compared to HC-IgG mice (p = 0.056). Disappointingly, no motor effects were observed in the treated mice. CONCLUSIONS: Here we provide the first in vivo evidence of anxiety-like behaviour in mice after i.c.v. injection of IgG containing anti-GlyR abs. Study Supported by: Colfuturo-Colciencias fellowship (AC-G). Oxford NIHR Biomedical Research Centre and the NHS National Commissioning Group. The University of Oxford holds patents and receives royalties and payments for antibody tests, AV and BL receive a share of royalties for antibody testing. Disclosure: Dr. Carvajal has nothing to disclose. Dr. Jacobson has nothing to disclose. Dr. Clover has nothing to disclose. Dr. Lang has received personal compensation for activities with Athena Diagnostics and RSR Ltd. as a consultant. Dr. Lang has received royalty payments from Athena Diagnostics. Dr. Upton has nothing to disclose. Dr. Vincent has received personal compensation for activities with Athena Diagnostics and RSR Ltd. UK as a consultant. Dr. Vincent has received royalty payments from Athena Diagnostics.