Antibody to aquaporin-4 in the long-term course of neuromyelitis optica.
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 [calle...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2008
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| _version_ | 1797102708171210752 |
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| author | Jarius, S Aboul-Enein, F Waters, P Kuenz, B Hauser, A Berger, T Lang, W Reindl, M Vincent, A Kristoferitsch, W |
| author_facet | Jarius, S Aboul-Enein, F Waters, P Kuenz, B Hauser, A Berger, T Lang, W Reindl, M Vincent, A Kristoferitsch, W |
| author_sort | Jarius, S |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T06:09:37Z |
| format | Journal article |
| id | oxford-uuid:ef0538aa-570f-4173-983a-abe29abc31a2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:09:37Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:ef0538aa-570f-4173-983a-abe29abc31a22022-03-27T11:37:15ZAntibody to aquaporin-4 in the long-term course of neuromyelitis optica.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ef0538aa-570f-4173-983a-abe29abc31a2EnglishSymplectic Elements at Oxford2008Jarius, SAboul-Enein, FWaters, PKuenz, BHauser, ABerger, TLang, WReindl, MVincent, AKristoferitsch, WNeuromyelitis 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. |
| spellingShingle | Jarius, S Aboul-Enein, F Waters, P Kuenz, B Hauser, A Berger, T Lang, W Reindl, M Vincent, A Kristoferitsch, W Antibody to aquaporin-4 in the long-term course of neuromyelitis optica. |
| title | Antibody to aquaporin-4 in the long-term course of neuromyelitis optica. |
| title_full | Antibody to aquaporin-4 in the long-term course of neuromyelitis optica. |
| title_fullStr | Antibody to aquaporin-4 in the long-term course of neuromyelitis optica. |
| title_full_unstemmed | Antibody to aquaporin-4 in the long-term course of neuromyelitis optica. |
| title_short | Antibody to aquaporin-4 in the long-term course of neuromyelitis optica. |
| title_sort | antibody to aquaporin 4 in the long term course of neuromyelitis optica |
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