P Waters1, Angela Vincent. 1. Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Abstract
BACKGROUND: Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease that predominantly affects the optic nerve and spinal cord. Since the discovery of a specific serum marker for NMO in 2004, and its subsequent identification as an antibody to aquaporin-4 (AQP-4), various methods have been developed to test for the antibodies in patients sera. OBJECTIVE: To assess the principal methods used to measure AQP-4 antibodies in patients sera, describe their contribution to neuromyelitis spectrum disease and examine their value in the early detection of disease. METHODS: We compared the published data on each assay and used the relapsing NMO cohort as a uniform patient group for direct assay comparison. RESULTS: The indirect immunofluorescence assay, a cellbased assay (CBA) and a fluorescence-based immunoprecipitation assay have broadly similar high sensitivities (86%, 91% and 83%) in the relapsing cohort, but the indirect immunofluorescence has a lower specificity (91%) compared with the other two (both 100% specific). CONCLUSIONS: The indirect immunofluorescence assay for NMO-IgG allows the detection of antibodies in routine screening, but the CBA for AQP-4 antibodies is the most sensitive. The fluoroimmunoprecipitation assay is a potentially high-throughput test for identifying positive sera and for serial estimations of antibody levels, but in its present form is slightly less sensitive. Overall, these assays are proving very useful in helping to diagnose those patients with longitudinally extensive transverse myelitis or recurrent optic neuritis who are likely to have relapsing NMO, including patients with myelopathy and Sjogrens syndrome, but it appears to be less often positive in patients with monophasic NMO.
BACKGROUND:Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease that predominantly affects the optic nerve and spinal cord. Since the discovery of a specific serum marker for NMO in 2004, and its subsequent identification as an antibody to aquaporin-4 (AQP-4), various methods have been developed to test for the antibodies in patients sera. OBJECTIVE: To assess the principal methods used to measure AQP-4 antibodies in patients sera, describe their contribution to neuromyelitis spectrum disease and examine their value in the early detection of disease. METHODS: We compared the published data on each assay and used the relapsing NMO cohort as a uniform patient group for direct assay comparison. RESULTS: The indirect immunofluorescence assay, a cellbased assay (CBA) and a fluorescence-based immunoprecipitation assay have broadly similar high sensitivities (86%, 91% and 83%) in the relapsing cohort, but the indirect immunofluorescence has a lower specificity (91%) compared with the other two (both 100% specific). CONCLUSIONS: The indirect immunofluorescence assay for NMO-IgG allows the detection of antibodies in routine screening, but the CBA for AQP-4 antibodies is the most sensitive. The fluoroimmunoprecipitation assay is a potentially high-throughput test for identifying positive sera and for serial estimations of antibody levels, but in its present form is slightly less sensitive. Overall, these assays are proving very useful in helping to diagnose those patients with longitudinally extensive transverse myelitis or recurrent optic neuritis who are likely to have relapsing NMO, including patients with myelopathy and Sjogrens syndrome, but it appears to be less often positive in patients with monophasic NMO.
Authors: Simone Mader; Andreas Lutterotti; Franziska Di Pauli; Bettina Kuenz; Kathrin Schanda; Fahmy Aboul-Enein; Michael Khalil; Maria K Storch; Sven Jarius; Wolfgang Kristoferitsch; Thomas Berger; Markus Reindl Journal: PLoS One Date: 2010-05-05 Impact factor: 3.240