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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2023.tde-15022024-124438
Document
Author
Full name
Renato Bussadori Tomioka
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2023
Supervisor
Committee
Silva, Clovis Artur Almeida da (President)
Buscatti, Izabel Mantovani
Aikawa, Nádia Emi
Sakamoto, Ana Paula
Title in Portuguese
Análise metabolômica em mulheres jovens com artrite idiopática juvenil
Keywords in Portuguese
Artrite idiopática juvenil
Biomarcadores
Metabolômica
Metotrexato
Subtipos de artrite idiopática juvenil
Abstract in Portuguese
O objetivo do presente trabalho foi avaliar os metabólitos bioquímicos quantitativos nas amostras de sangue periférico de pacientes com artrite idiopática juvenil (AIJ) e indivíduos controle saudáveis. Neste estudo transversal foram incluídas 33 mulheres pós-púberes com AIJ (21 delas em tratamento com metotrexato-MTX e 12 sem tratamento) e 28 controles saudáveis e com idade compatível. As análises de metabolômica foram realizadas pela espectrometria de massas Tandem com ionização por eletrospray (ESI-MS) com o intuito de identificar possíveis alterações nas vias bioquímicas no soro de pacientes com AIJ. O uso contínuo de MTX foi associado a um aumento nas concentrações de carnitina livre em todas as pacientes com os diferentes subtipos de AIJ [21,74(12,7-35,2) vs. 27,49(14,5-41,3) M/L, p=0,02], sugerindo uma melhora no metabolismo mitocondrial e na função da absorção intestinal. No entanto, foi constatada uma diminuição do metabolismo mitocondrial nos subtipos de AIJ poliarticular e sistêmica, com diminuição na concentração de diversas acilcarnitinas (p<0,05). Em conclusão, este estudo foi capaz de identificar padrões de assinaturas metabólicas diferentes nas pacientes com AIJ em tratamento com MTX. Nossos resultados indicam, ainda, que o uso do MTX está associado com maior eficiência na função mitocondrial
Title in English
Metabolomics in juvenile idiopathic arthritis: a distinct profile in patients under methotrexate
Keywords in English
Biomarkers
Juvenile idiopathic arthritis
Juvenile idiopathic arthritis subtypes
Metabolomics
Methotrexate
Abstract in English
The objective of the present study was to evaluate biochemical quantitative metabolites in peripheral blood serum samples of juvenile idiopathic arthritis (JIA) patients and healthy controls. A cross-sectional study included 33 post-pubertal JIA (21 without and 12 with methotrexate-MTX) women and 28 age-matched healthy controls. Metabolomic analyses based on targeted electrospray ionization tandem mass spectrometry was used to identify possible biochemical pathway modifications in serum from JIA patients. The mean current age (p=0.065) was similar in JIA patients and healthy controls. Current MTX use in all subtypes of JIA patients was associated with an increase in concentrations of free carnitine [21.74(12.7-35.2) vs. 27.49(14.5-41.3)M/L, p=0.02], suggesting an enhanced mitochondrial metabolism and intestinal absorptive function. In contrast, a decreased mitochondrial metabolism was observed in polyarticular and systemic JIA subtypes, with a decrease of several acylcarnitines concentrations(p<0.05). In conclusion, the present study identified a distinctive pattern of serum metabolic signatures in JIA patients under MTX therapy. Our findings indicate that MTX use is associated with a more efficient mitochondrial function
 
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Publishing Date
2024-02-19
 
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