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

Jarius S, Aboul-Enein F, Waters P, Kuenz B, Hauser A, Berger T, Lang W, Reindl M, Vincent A, Kristoferitsch W - Brain (2008)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Neurosciences Group, Weatherall Institute of Molecular Medicine, and Department of Neurology, John Radcliffe Hospital, University of Oxford, UK.

ABSTRACT
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.

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Increase in AQP4-Ab levels during relapse is not paralleled by a rise in other autoimmune autoantibodies. ♦ = AQP4-Ab;  = AChR-Ab;  = TG-Ab;  = TPO-Ab;  = clinical relapse;  = intravenous methylprednisolone;  = prednisolone;  = azathioprine;  = cyclophosphamide;  = mitoxantrone.
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Figure 3: Increase in AQP4-Ab levels during relapse is not paralleled by a rise in other autoimmune autoantibodies. ♦ = AQP4-Ab;  = AChR-Ab;  = TG-Ab;  = TPO-Ab;  = clinical relapse;  = intravenous methylprednisolone;  = prednisolone;  = azathioprine;  = cyclophosphamide;  = mitoxantrone.

Mentions: In one patient with pre-existing autoimmune myasthenia gravis and autoimmune thyroditis, AQP4-Ab was determined in parallel with antibodies to AChR, TPO and TG. While AQP4-Ab levels increased during two relapses by 42% and 67% compared with the first available value, all other autoantibodies titres had declined at that time (AChR-Ab by 54.1%; TPO-Ab 32%; TG-Ab 45.7%) (Fig. 3). Moreover, AQP4-Ab levels rose by 49.8% over the observation period of 2323 days, while AChR-, TPO- and TG-Ab concentrations declined by 90%, 94.2% and 94.3%, respectively, under therapy with cyclophosphamide. While AChR-, TPO- and TG-Ab titres correlated well over time (r2 = 0.9, 0.95 and 0.99, respectively; P < 0.005), no correlation of AQP4-Ab levels with any of these autoantibodies was found (r2 < 0.04).


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

Jarius S, Aboul-Enein F, Waters P, Kuenz B, Hauser A, Berger T, Lang W, Reindl M, Vincent A, Kristoferitsch W - Brain (2008)

Increase in AQP4-Ab levels during relapse is not paralleled by a rise in other autoimmune autoantibodies. ♦ = AQP4-Ab;  = AChR-Ab;  = TG-Ab;  = TPO-Ab;  = clinical relapse;  = intravenous methylprednisolone;  = prednisolone;  = azathioprine;  = cyclophosphamide;  = mitoxantrone.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2577801&req=5

Figure 3: Increase in AQP4-Ab levels during relapse is not paralleled by a rise in other autoimmune autoantibodies. ♦ = AQP4-Ab;  = AChR-Ab;  = TG-Ab;  = TPO-Ab;  = clinical relapse;  = intravenous methylprednisolone;  = prednisolone;  = azathioprine;  = cyclophosphamide;  = mitoxantrone.
Mentions: In one patient with pre-existing autoimmune myasthenia gravis and autoimmune thyroditis, AQP4-Ab was determined in parallel with antibodies to AChR, TPO and TG. While AQP4-Ab levels increased during two relapses by 42% and 67% compared with the first available value, all other autoantibodies titres had declined at that time (AChR-Ab by 54.1%; TPO-Ab 32%; TG-Ab 45.7%) (Fig. 3). Moreover, AQP4-Ab levels rose by 49.8% over the observation period of 2323 days, while AChR-, TPO- and TG-Ab concentrations declined by 90%, 94.2% and 94.3%, respectively, under therapy with cyclophosphamide. While AChR-, TPO- and TG-Ab titres correlated well over time (r2 = 0.9, 0.95 and 0.99, respectively; P < 0.005), no correlation of AQP4-Ab levels with any of these autoantibodies was found (r2 < 0.04).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Neurosciences Group, Weatherall Institute of Molecular Medicine, and Department of Neurology, John Radcliffe Hospital, University of Oxford, UK.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus