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Development of the nanoimmunosensor-AQP461-70 for the highly specific and sensitive diagnosis of neuromyelitis optica spectrum disorders

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Ariana de Souza Moraes dos Santos
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Medicina Tropical de São Paulo (IMT)
Defense date:
Examining board members:
Fabio de Lima Leite; Guilherme Sciascia do Olival; Camila Malta Romano; Marcelo de Assumpcao Pereira da Silva
Advisor: Fabio de Lima Leite; Doralina Guimarães Brum Souza

Neuromyelitis optica spectrum disorders (NMOSD) are inflammatory syndromes of the central nervous system, characterized by myelitis and optic neuritis events, which affect predominantly spinal cords and optic nerves. A precise diagnosis for 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, four AQP4 external loop peptides (AQP461-70, AQP4131-140, AQP4141-150, and AQP4201-210) were tested with an atomic force microscopy nanoimmunosensor to develop a diagnostic assay. The results show the highest reactivity with AQP461-70-nanoimunosensor. This assay was effective in detecting AQP4-Ab in sera of NMOSD patients with 100% specificity (95% CI 63.06-100.00), 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. AQP461-70 sensitivity was 81.25% (95% CI 56.50-99.43). This sensitivity value was higher than the obtained by CBA method. The results with the AQP461-70-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 for NMOSD diagnosis purposes. (AU)

FAPESP's process: 15/05283-6 - Nanoimmunosensors development to neuromyelitis optica survey and detection
Grantee:Ariana de Souza Moraes
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)