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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.

Original publication

DOI

10.1093/brain/awn240

Type

Journal article

Journal

Brain

Publication Date

11/2008

Volume

131

Pages

3072 - 3080

Keywords

Adolescent, Adult, Antibodies, Monoclonal, Antibodies, Monoclonal, Murine-Derived, Antigens, CD19, Aquaporin 4, Autoantibodies, Autoimmune Diseases, Azathioprine, Biomarkers, Female, Follow-Up Studies, Glucocorticoids, Humans, Immunosuppressive Agents, Lymphocyte Count, Male, Middle Aged, Neuromyelitis Optica, Recurrence, Retrospective Studies, Rituximab, Young Adult