Please use this identifier to cite or link to this item: http://hdl.handle.net/1843/BUBD-A8WMWB
Type: Tese de Doutorado
Title: Avaliação da composição corporal, dos níveis de citocinas pró-inflamatórias e de proteínas do sistema osteoprotegerina-rankl em pacientes com psoríase e controles
Authors: Michelle dos Santos Diniz
First Advisor: Maria Marta Sarquis Soares
First Co-advisor: Jackson Machado Pinto
First Referee: Flavia Vasques Bittencourt
Second Referee: Marcio Weissheimer Lauria
Third Referee: Bárbara Campolina Carvalho silva
Abstract: Introducao: A psoriase e uma doenca inflamatoria cronica da pele que ocorre em cerca e 1,5-2% da populacao mundial. Diversas doencas ja foram comprovadamente associadas a psoriase como doencas cardiovasculares, diabete melito e dislipidemia. Essa associacao esta relacionada ao processo inflamatorio cronico. Avancos atuais napatogenese da osteoporose tem observado a participacao de citocinas como IFN-, IL-6 e TNF- que tambem participam da patogenese da psoriase. Questiona-se se a psoriase nao poderia comprometer a densidade mineral ossea (DMO). Objetivos: Avaliar a frequencia de adiposidade atraves do indice de massa corporal (IMC), circunferencia abdominal (CA) e absorciometria por dupla emissao de raios-x(DXA) nos pacientes com psoriase e controles e determinar a concordancia entre essas diferentes medidas de adiposidade. Avaliar e comparar a composicao corporal nos pacientes com psoriase e controles. Determinar os niveis sericos das citocinas inflamatorias (TNF-, INF-, IL-2, IL-4, IL-12, IL-23, IL-10, IL-17A e IL-6) e dos marcadores do metabolismo osseo CTx (telopeptideo carboxiterminal do colageno), do ligante do receptor do ativador do fator nuclear Kappa B (RANKL), da osteoprotegerina (OPG) nos pacientes com psoriase e nos controles. Correlacionar os valores das citocinas pro-inflamatorias e dos marcadores osseos com a DMO e com o conteudo mineral osseo (CMO) nos pacientes estudados. Metodos: De maio a novembro de 2012 foram incluidos 42 pacientes portadores de psoriase e 41 controles pareados por sexo e idade. Os pacientes foram submetidos ao exame clinico com avaliacao do IMC e CA, a DXA, e a dosagens sericas de marcadores osseos e de citocinas inflamatorias. Na comparacao entre os casos e controles foram utilizados os testes de Pearson, exato de Fisher e de Mann-Whitney. A diferenca entre os diferentes metodos de avaliacao da obesidade foi avaliada por meio do teste de McNemar. Para testar o nivel de concordancia entre as variaveis, foi utilizado o kappaponderado. Apos analise univariada procedeu-se a analise multivariada para se identificar os fatores associados a DMO e CMO nos pacientes. Em todas as analises considerou-se um nivel de significancia de 5%. Foi utilizado o software SPSS 15.0. Resultados: Os pacientes com psoriase apresentaram mediana de idade de 47 anos, sendo 59,5% do sexo masculino. O tempo mediano de doenca relatado foi de dez anos. Trinta e sete pacientes (88%) apresentaram psoriase classificada como leve. Os controles apresentaram mediana de idade de 38 anos e 53,7% eram do sexo masculino. Nao houve diferenca entre os grupos em relacao ao sexo (p=0,590) e idade (p=0,090). Nao houve diferenca na prevalencia de obesidade entre casos e controles pelos diferentes metodos. Tanto o IMC e a CA tiveram baixa concordancia com as medidas de gordura corporal avaliada pela DXA. Os casos apresentaram uma tendencia de menor CMO (p = 0,059). A analise estratificada por sexo mostrou que os pacientes do sexo masculino apresentaram menor CMO (p =0,007) e menor DMO (p = 0,027) emrelacao aos controles do mesmo sexo. Nao foi encontrada diferenca entre os grupos em relacao a outros indices de composicao corporal. Pacientes com psoriase apresentaram niveis mais elevados de OPG, IL-12, IL-10, IL-6, IL-4 e IL-2 (p<0,05) em relacao aos controles. Nao se observou diferenca entre os grupos para as dosagens de IL-23,RANK-L, CTX, IL-17A, IFN- e TNF-. Pacientes com psoriase em tratamento sistemico apresentaram niveis de TNF- menores do que pacientes apenas em tratamento topico. Nos pacientes com psoriase observou-se correlacao inversa da OPG, IL-6, IL-17A e IL-23 com as variaveis de DMO e CMO. Conclusao: A DXA teve maior capacidade de identificar obesidade em comparacao com o IMC e CA, tanto nos pacientes com psoriase e os controles. Pacientes do sexo masculino com psoriase apresentaram menor CMO que controles. Pacientes compsoriase apresentam niveis mais elevados de importantes citocinas inflamatorias na patogenese da psoriase e tambem de OPG, provavelmente uma resposta compensatoria ao maior estimulo a osteoclastogenese que poderia ocorrer nesses pacientes. Acorrelacao inversa da DMO e do CMO com importantes citocinas da patogenese da psoriase sinaliza a possibilidade da influencia negativa dessas citocinas no metabolismo osseo.
Abstract: Introduction: Psoriasis is a chronic inflammatory skin disease that occurs in about 1.5- 2% of the world population. Several diseases have been associated with psoriasis as cardiovascular diseases, diabetes mellitus and dyslipidemia. This association is related to the chronic inflammatory process. Current advances in the pathogenesis ofosteoporosis have observed the participation of cytokines such as IFN-, IL-6 and TNF- that are also involved in the pathogenesis of psoriasis. It has been questioned if psoriasis could compromise bone mineral density (BMD). Objectives: Assess the frequency of adiposity through the body mass index (BMI), waist circumference (WC) and absorptiometry dual energy x-ray (DXA) in psoriasis patients and controls and determine the correlation between these different measures of adiposity. Assess and compare the body composition of patients with psoriasis andcontrols. To determine the serum levels of pro-inflammatory cytokines (TNF-, INF- , IL-2, IL-4, IL-12, IL-23, IL-10, IL-17A and IL-6) and bone metabolism markers such as CTx (carboxyterminal telopeptide of collagen), the binding of the activator of nuclear factor kappa B (RANKL), osteoprotegerin (OPG) in patients with psoriasis and controls. Correlate the values of these pro-inflammatory cytokines and bone markerswith BMD and bone mineral content (BMC) in the patients studied.Methods: From May to November 2012, 42 patients with psoriasis and 41 controls matched for sex and age were included in the study. All of them underwent clinical examination with assessment of BMI and WC, the DXA, and dosage of serum bone markers and inflammatory cytokines. In the comparison between cases and controls, Pearson's, Fisher's exact and Mann-Whitney tests were used. The agreement betweenthe different methods of assessing obesity was evaluated using the weighted kappa coefficient and the difference between these methods was evaluated using the McNemar test. After univariate analysis proceeded to the multivariate analysis to identify the factors associated with BMD and BMC in patients. In all analyzes we considered asignificance level of 5%. SPSS 15.0 software was used. Results: Patients with psoriasis had a median age of 47 years, 59.5% male. The mediantime of psoriasis reported was ten years. Thirty-seven patients (88%) were classified as mild psoriasis. The controls had a median age of 38 years and 53.7% were male. There was no difference in the prevalence of obesity among cases and controls by different methods. Both BMI and the WC had poor agreement with the body fat measures assessed by DXA. The cases showed a trend toward lower total BMC (p = 0.059). Stratified analysis by gender showed that male patients had lower BMC (p=0.007) and lower BMD (p = 0.027) compared to controls of the same gender. No difference between groups was found in relation to other indices of body composition. Patients with psoriasis had higher levels of OPG, IL-12, IL-10, IL-6, IL-4 and IL-2 (p <0.05) compared to controls. There was no difference between groups for the dosages of IL-23, RANK-L, CTX, IL-17A, IFN- and TNF-. Patients with psoriasis under systemictreatment had lower levels of TNF- than patients only under topical treatment.Psoriatic patients showed an inverse correlation of OPG, IL-6, IL-17 and IL-23 with the variables related to DMO and CMO. Conclusion: DXA was more effective in identifying obesity compared with the CA andBMI, both in psoriasis patients and controls. Male patients with psoriasis had lower BMC than controls. Psoriasis patients have higher levels of inflammatory cytokines that are important in the pathogenesis of psoriasis as well as OPG, probably a compensatory response to increased osteoclastogenesis that may be present in these patients. Theinverse correlation between BMD and BMC with important cytokines in thepathogenesis of psoriasis signals the possibility of a negative influence of these cytokines on bone metabolism.
Subject: Absorciometria de Fóton
Índice de massa corporal
Circunferência abdominal
Estudos de casos e controles
Adiposidade
Psoríase/complicações
Medicina
language: Português
Publisher: Universidade Federal de Minas Gerais
Publisher Initials: UFMG
Rights: Acesso Aberto
URI: http://hdl.handle.net/1843/BUBD-A8WMWB
Issue Date: 29-Sep-2015
Appears in Collections:Teses de Doutorado

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