Antibody to aquaporin-4 in the long-term course of neuromyelitis optica

Journal article

Neuromyelitis optica (NMO) is a severe inflammatory CNS disorder of putative autoimmune aetiology, which predominantly affects the spinal cord and optic nerves. Recently, a highly specific serum reactivity to CNS microvessels, subpia and Virchow-Robin spaces was described in patients with NMO [called NMO-IgG (NMO-immunoglobulin G)]. Subsequently, aquaporin-4 (AQP4), the most abundant water channel in the CNS, was identified as its target antigen. Strong support for a pathogenic role of the antibody would come from studies demonstrating a correlation between AQP4-Ab (AQP4-antibody) titres and the clinical course of disease. In this study, we determined AQP4-Ab serum levels in 96 samples from eight NMO-IgG positive patients (median follow-up 62 months) in a newly developed fluorescence-based immunoprecipitation assay employing recombinant human AQP4. We found that AQP4-Ab serum levels correlate with clinical disease activity, with relapses being preceded by an up to 3-fold increase in AQP4-Ab titres, which was not paralleled by a rise in other serum autoantibodies in one patient. Moreover, AQP4-Ab titres were found to correlate with CD19 cell counts during therapy with rituximab. Treatment with immunosuppressants such as rituximab, azathioprine and cyclophosphamide resulted in a marked reduction in antibody levels and relapse rates. Our results demonstrate a strong relationship between AQP4-Abs and clinical state, and support the hypothesis that these antibodies are involved in the pathogenesis of NMO. © 2008 The Author(s).

Authors: Jarius, S; Aboul-Enein, F; Waters, P; Kuenz, B; Hauser, A

• Journal: Brain
• Volume: 131
• Issue: 11
• Pages: 3072-3080
• Publication date: 2008-11-01
• DOI: 10.1093/brain/awn240
• EISSN: 1460-2156
• ISSN: 0006-8950
• Language: English
• Keywords: Devic syndrome; Long-term follow-up; Neuromyelitis optica; Longitudinally extensive transverse myelitis; NMO-IgG; Aquaporin-4 antibody