Avaliação das manifestações clínicas, da cronicidade e da expressão gênica na febre chikungunya

• Ano de defesa: 2020
• Autor(a) principal: Océa, Regina Adalva de Lucena Couto
• Orientador(a): Almeida, Roque Pacheco de
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Programa de Pós-Graduação: Pós-Graduação em Ciências da Saúde
• Palavras-chave em Português: Ciências da saúde; Febre chikungunya; Artrite; Inflamação; Expressão gênica; RNA-seq.
• Palavras-chave em Inglês: Health Sciences; Chikungunya fever; Arthritis; Inflammation; Gene expression; RNA-seq.
• Área do conhecimento CNPq: CIENCIAS DA SAUDE
• Link de acesso: http://ri.ufs.br/jspui/handle/riufs/17131

Introduction: Chikungunya Fever (CF) has become a recent epidemic in Brazil, especially in the Northeast region. In addition to fever, rash, the appearance of diffuse arthralgias and arthritis, often incapacitating with evolution to chronicity in 40% to 87% of cases. Despite this, there are few studies evaluating the patophisiological aspects and factors associated with chronicity, including the analysis of molecular signatures. Objective: To identify the clinical characteristics, the aspects associated with joint chronicity and to analyze the type of gene expression in the evolution of this disease. Method: Prospective cohort study followed up at the Rheumatology Service of Hospital Universitário de Sergipe (HU/UFS-SE) for 24 months. Clinical evaluation, collection of general laboratory tests, and evaluation of gene expression were carried out by analyzing the transcriptome, through RNA sequencing, using the deep-sequencing technique (RNA-seq). These collections were made at the molecular biology laboratory of HU-SE in partnership with the Butantan Institute of São Paulo, where the RNA-seq was analyzed. Chronic and non-chronic groups were compared. Categorical variables were expressed as absolute frequencies and percentages. For the comparison between the groups, the T-Student test was used for independent parametric data or the Mann-Whitney test for non-parametric data. For the regression models, Odds Ratio and Risk Ratio were calculated, and a multivariable logistic regression was subsequently performed. For the probability analysis, the Kaplan-Meier curve was performed. For all statistical analyzes, a confidence interval greater than 95% (p <0.05) was considered. Results: 246 CF patients were analyzed, 92.3% of whom had their diagnosis confirmed by qRT-PCR, with a chronicity rate of 54.3%. The main factors associated with chronification were age, female gender, arthralgia, myalgia, lymphadenopathy and use of NSAIDs (p<0.005). After an adjusted logistic regression, it was identified that only age, female gender, lymphadenopathy and use of NSAIDs remained as independent factors. The Kaplan Meier survival curve identified that after 90 days the frequency of chronicity was 10.5%, gradually increasing, reaching 30% in the first year. The main chronic rheumatological symptoms were non-inflammatory diseases, 25% of DAIC and 5% of chronic autoimmune disease (Rheumatoid Arthritis and Psoriatic Arthritis). The positivity of qRT-PCR was observed in 73% of chronic cases, however, no clinical and evolution differences were observed in the comparison of patients with positive and negative qRT-PCR. Transcriptome analysis was performed in 39 patients in the acute phase and 6 of the chronic phase. Among the main genes observed, EiF (eukaryotic translation initiation factors) and IRF7 are important in the viral replication process, in addition to the DDX3Y and EIF1AY genes, related to chronic evolution. Conclusion: Osteoarticular morbidity in CF, mainly due to its chronic aspect, has uncertainties in its pathophysiology. Our findings demonstrate that exacerbated acute manifestations and advanced age, female gender, and lymphadenopaty are factors associated with chronicity. The identification of some IFN-inducing genes and the EIFs in the presence of the disease may encourage future studies to clarify the treatment and prevention of CF.