Publication date: Nov 06, 2019
A precise diagnosis for neuromyelitis optica spectrum disorders (NMOSD) is crucial to improve patients’ prognostic, which requires highly specific and sensitive tests. The cell-based assay with a sensitivity of 76% and specificity of 100% is the most recommended test to detect anti-aquaporin-4 antibodies (AQP4-Ab). Here, we tested four AQP4 external loop peptides (AQP4, AQP4, AQP4, and AQP4) with an atomic force microscopy nanoimmunosensor to develop a diagnostic assay. We obtained the highest reactivity with AQP4-nanoimunosensor. This assay was effective in detecting AQP4-Ab in sera of NMOSD patients with 100% specificity (95% CI 63.06-100), determined by the cut-off adhesion force value of 241.3 pN. NMOSD patients were successfully discriminated from a set of healthy volunteers, patients with multiple sclerosis, and AQP4-Ab-negative patients. AQP4 sensitivity was 81.25% (95% CI 56.50-99.43), slightly higher than with the CBA method. The results with the AQP4-nanoimmunosensor indicate that the differences between NMOSD seropositive and seronegative phenotypes are related to disease-specific epitopes. The absence of AQP4-Ab in sera of NMOSD AQP4-Ab-negative patients may be interpreted by assuming the existence of another potential AQP4 peptide sequence or non-AQP4 antigens as the antibody target.
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de Souza Moraes, A., Brum, D.G., Ierich, J.C.M., Higa, A.M., Assis, A.S.J., Miyazaki, C.M., Shimizu, F.M., Peroni, L.A., Machini, M.T., Barreira, A.A., Ferreira, M., Oliveira, O.N., and Leite, F.L. A highly specific and sensitive nanoimmunosensor for the diagnosis of neuromyelitis optica spectrum disorders. 19430. 2019 Sci Rep (9):1.