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Doctoral Thesis
DOI
https://doi.org/10.11606/T.17.2022.tde-03012023-110007
Document
Author
Full name
Flavio Falcão Lima de Souza
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2022
Supervisor
Committee
Oliveira, Renê Donizeti Ribeiro de (President)
Veras, Flávio Protásio
Carvalho, Luciana Martins de
Rodrigues, Maria Carolina de Oliveira
Title in Portuguese
Avaliação de survivina e armadilhas extracelulares de neutrófilos no líquido sinovial como biomarcadores na artrite reumatoide
Keywords in Portuguese
Apoptose
Artrite reumatoide
Biomarcadores
NETs
Survivina
Abstract in Portuguese
Introdução: a resistência do pannus à apoptose é uma característica importante que resulta em invasão e erosão óssea na artrite reumatoide (AR). A survivina, uma proteína antiapoptótica produzida por fibroblastos sinoviais, é útil como biomarcador de diagnóstico e dano articular na AR. Os neutrófilos sinoviais apresentam apoptose tardia e são responsáveis por lesar diretamente o tecido articular, atuando através da liberação de grânulos enzimáticos, espécies reativas de oxigênio e armadilhas extracelulares de neutrófilos (NETs). NETs são reconhecidas como fonte de autoantígenos citrulinados na AR. Objetivos: quantificar survivina e NETs no líquido sinovial (LS) de pacientes com AR e osteoartrite (OA) e avaliar se há correlação das quantificações com o diagnóstico, gravidade e atividade da AR. Métodos: foi realizado um estudo observacional transversal, no qual foram incluídos 32 pacientes com AR e 16 com OA. Foram obtidos dados clínicos, laboratoriais e radiográficos, além de análises de rotina do LS e dosagem de survivina e NETs sinoviais. A atividade da AR foi avaliada usando DAS28. Resultados: A survivina foi encontrada elevada no LS do grupo AR em comparação com o grupo OA (mediana 356,9 vs 49,9 pg/mL, p=0,0006). A mediana de NETs foi de 100,7 e 49,7 ng/mL (p=0,004) para os grupos AR e OA, respectivamente. As curvas ROC mostraram os seguintes valores para medidas de survivina e NETs: AUC de 79% e 75%, respectivamente, com sensibilidade de 75% e especificidade de 78% para ambos. Não houve correlação entre os valores de survivina e NETs para ambos os grupos. Discussão: Foi encontrada uma associação entre os níveis de survivina e NETs no LS e o diagnóstico de AR, mas não com erosões ósseas ou atividade da doença. Não houve correlação entre survivina e NETs no LS, pelo que supomos que a resistência à apoptose, mediada pela survivina, e a netose podem não estar diretamente relacionadas na fisiopatologia da AR.
Title in English
Evaluation of survivin and extracellular neutrophil traps in synovial fluid as biomarkers in rheumatoid arthritis
Keywords in English
Apoptosis
Biomarkers
NETs
Rheumatoid arthritis
Survivin
Abstract in English
Introduction: the pannus resistance to apoptosis is a key feature for invasion leading to bone erosion in rheumatoid arthritis (RA). Survivin, an antiapoptotic protein produced by RA fibroblast-like synoviocytes, is useful as biomarkers of diagnosis and joint damage in RA. Synovial neutrophils present delayed apoptosis and are responsible for directly injuring joint tissue, acting through the release of enzymatic granules, reactive oxygen species and neutrophil extracellular traps (NETs). NETs are recognized as a source of citrullinated autoantigens in RA. Aims: to quantify survivin and NETs in SF of patients with RA and osteoarthritis (OA) and to assess whether there is a correlation of the quantifications with the diagnosis, severity and activity of RA. Methods: we performed a cross-sectional, observational study, in which 32 patients with RA and 16 with OA were included. Clinical, laboratory and radiographic data were obtained, in addition to routine analysis of SF and the dosage of SF survivin and NETs. RA activity was assessed using DAS28. Results: Survivin was found to be elevated in the synovial fluid of the AR group compared to the OA group (median 356.9 vs 49.9 pg/mL, p=0.0006). The median NETs were 100.7 and 49.7 ng/mL (p=0.004) for RA and OA groups, respectively. ROC curves showed the following values for measurements of survivin and NETs: AUC of 79% and 75% respectively, with sensitivity of 75% and specificity of 78% for both. There was no correlation between survivin and NETs values for both groups. Discussion: We found an association between levels of survivin and NETs in SF and the diagnosis of RA, but not with bone erosions or disease activity. There was no correlation between survivin and NETs in SF, for what we suppose that resistance to apoptosis, mediated by survivin, and netosis may not be directly related in the pathophysiology of RA.
 
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Publishing Date
2023-01-16
 
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