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Doctoral Thesis
DOI
10.11606/T.5.2018.tde-12012018-101926
Document
Author
Full name
Thiago Costa Pamplona da Silva
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Shinjo, Samuel Katsuyuki (President)
Borba Neto, Eduardo Ferreira
Reis Neto, Edgard Torres dos
Souza, Fernando Henrique Carlos de
Title in Portuguese
Perfil de citocinas angiogênicas séricas em pacientes com dermatomiosite
Keywords in Portuguese
Citocinas
Dermatomiosite
Doenças musculares
Estudos transversais
Miosite
Vasos sanguíneos
Abstract in Portuguese
Introdução: Até o presente momento, há escassez de estudos que avaliem os níveis séricos de citocinas angiogênicas em pacientes com dermatomiosite (DM), uma miosite autoimune sistêmica que tem como fisiopatogênese a vasculopatia. Portanto, os objetivos do presente estudo foram: (a) analisar sistematica e simultaneamente os níveis séricos de angiogenin (ANG), angiopoietin (ANGPT) -1, vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) -1 e -2 e platelet derived growth factor (PDGF) -AA e -BB em pacientes com DM; (b) correlacionar o nível sérico destas citocinas com as características clínico-laboratoriais, alterações metabólicas e atividade da DM. Pacientes e métodos: Estudo transversal, único centro, no qual foram incluídos, no período de 2012 a 2014, 48 pacientes consecutivos com DM definida (Bohan e Peter, 1975), entre 18 e 45 anos de idade, e em seguimento regular na nossa Instituição. Foram excluídos pacientes com condições clínicas relacionadas à DM (como sequelas de doença e tratamento prolongado) ou secundárias a outras causas que poderiam influenciar na interpretação dos resultados das citocinas avaliadas, seja por apresentarem variações hormonais ou por estarem relacionados ao mecanismo de inflamação e/ou angiogênese. Os pacientes foram pareados por sexo, idade e etnia com 48 indivíduos saudáveis (grupo controle). A análise das citocinas séricas foi realizada por imunoensaio multiplex. Os parâmetros da atividade da DM foram baseados nos escores estabelecidos por International Myositis Assessment & Clinical Studies Group (IMACS). Resultados: A distribuição de sexo e a etnia foram comparáveis entre os grupos DM e controle assim como a média de idade (33,3±7,6 vs. 35,8±8,2 anos, respectivamente), e a mediana de duração de doença foi de 1 ano. No grupo DM, os níveis séricos de FGF-1 e FGF-2 (P < 0,001, P < 0,001, respectivamente) estavam elevados, enquanto os níveis de VEGF e PDGF-AA (P=0,009 e P=0,022, respectivamente) estavam reduzidos. Os níveis de ANG, ANGPT-1 e PDGFBB foram semelhantes em ambos os grupos. Houve uma tendência para correlação positiva entre as citocinas (com exceção de VEGF e PDGF-BB) e os parâmetros de atividade da DM, enquanto FGF-2 apresentou correlação negativa. Além disso, o FGF-1 correlacionou-se fortemente com manifestações cutâneas da dermatomiosite. Conclusões: Os dados atuais reforçam a importância das citocinas angiogênicas nos mecanismos de vasculopatia da DM, especialmente em condições de atividade cutânea e adequado tratamento medicamentoso. Estudos adicionais serão necessários para validar os dados obtidos no presente trabalho
Title in English
Serum angiogenic cytokine features in patients with dermatomyositis
Keywords in English
Blood vessels
Cross-sectional studies, Myositis
Cytokines
Dermatomyositis
Muscle diseases
Abstract in English
Introduction: Until now, there are few studies evaluating serum levels of angiogenic cytokines in patients with dermatomyositis (DM), a systemic autoimmune myositis that has vasculopathy as its physiopathogenesis. Therefore, the aims of the present study were: (a) to analyze systematically and simultaneously serum levels of angiogenin (ANG), angiopoietin (ANGPT) -1, vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) -1 and -2, and platelet derived growth factor (PDGF) -AA and -BB in patients with DM; (b) to correlate the serum level of these cytokines with the clinical and laboratory features, metabolic alterations and DM activity. Patients and methods: This is an one-center cross sectional study, in which 48 consecutive patients with defined DM (Bohan and Peter, 1975) aged 18 to 45 years and regularly followed up at our Institution were included from 2012 to 2014. Patients with clinical conditions related to DM (as sequelae of disease and prolonged treatment) or secondary to other causes that could influence the results interpretation of the evaluated cytokines were excluded, either because of hormonal variations or relationship with inflammation mechanism and/or angiogenesis. Patients were gender-, age- and ethnicity-matched with 48 healthy individuals (control group). The serum levels of cytokines analyses were performed by multiplex immunoassay. The parameters of DM activity were based on the scores established by the International Myositis Assessment & Clinical Studies Group (IMACS). Results: The gender and ethnicity were comparable between DM and control groups as soon as the mean age (33.3±7.6 vs. 35.8±8.2 years, respectively), and the median disease duration was 1 year. The serum levels of FGF-1 and FGF-2 (P < 0.001 and P < 0.001, respectively) were higher in DM group, whereas the levels of VEGF and PDGF-AA (P=0.009 and P=0.022, respectively) were lower in DM group. The levels of ANG, ANGPT-1 and PDGF-BB were similar in both groups. There was a tendency for cytokines (with the exceptions of VEGF and PDGF-BB) to correlate positively with DM activity parameters, whereas FGF-2 correlated inversely. Moreover, FGF-1 strongly correlated with the cutaneous manifestations of DM. Conclusion: The current data reinforce the importance of angiogenic cytokines in DM vasculopathy mechanisms, especially in conditions of cutaneous activity and adequate drug treatment. Additional studies will be needed to validate the data obtained in this work
 
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Publishing Date
2018-01-12
 
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