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| Author(s): |
Ariana de Souza Moraes dos Santos
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Medicina Tropical de São Paulo (IMT) |
| Defense date: | 2019-08-12 |
| Examining board members: |
Fabio de Lima Leite;
Guilherme Sciascia do Olival;
Camila Malta Romano;
Marcelo de Assumpcao Pereira da Silva
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| Advisor: | Fabio de Lima Leite; Doralina Guimarães Brum Souza |
| Abstract | |
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 dos Santos |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |