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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2023.tde-24042024-162944
Document
Author
Full name
Walter Refkalefsky Loureiro
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2023
Supervisor
Committee
Quaresma, Juarez Antônio Simões (President)
Falcão, Luiz Fábio Magno
Carneiro, Francisca Regina Oliveira
Pagliari, Carla
Title in Portuguese
Imunoexpressão de fatores de crescimento e citocinas em lesões cutâneas da doença de Jorge Lobo.
Keywords in Portuguese
Antígenos de resposta imune
Biomarcadores
Doença de Jorge Lobo
Lacaziose
Lobomicose
Matriz extracelular
Abstract in Portuguese
A doença de Jorge Lobo é uma micose profunda que se apresenta localizada sobretudo nos membros inferiores, de evolução crônica e êxito terapêutico muito limitado. Em virtude da cronicidade da doença de Jorge Lobo, com permanência do fungo no tecido por longo período, é de suma importância a ativação do sistema imunológico do hospedeiro e, apesar de alguns trabalhos já terem descrito o padrão de resposta imune local, pouco se sabe sobre a participação e o possível papel da interação de citocinas e fatores de crescimento na sua patogenia. Realizou-se a quantificação de 8 citocinas e fatores de crescimento nas lesões cutâneas da doença de Jorge Lobo utilizando a marcação imuno-histoquímica, comparando-as com o grupo controle. Foram também analisadas as características clínico-demográficas dos pacientes investigados. Dos 16 pacientes portadores de Doença de Jorge Lobo analisados, 81,25% eram do gênero masculino, 81,25% tinham a faixa etária entre 40 e 60 anos e a localização das lesões em 43,75 % dos casos era nos membros inferiores, 25% na orelha, sendo todos os pacientes paraenses. Foi nítido e estatisticamente significativo o predomínio da expressão dos marcadores FGF, TGF- e NGF caracterizando um perfil antinflamatório que contribui para a evasão imune e sobrevivência do fungo mesmo dentro de um ambiente pró-inflamatório caracterizado pela maior imunomarcação de TNF-, IL-1 , IL-1 , EGF e PDGF quando comparados ao grupo controle. Este ambiente inflamatório é ineficaz na destruição do fungo, porém suficiente para remodelar a matriz extracelular de maneira crônica gerando as alterações clínicas e histopatológicas características da doença. Este trabalho coloca mais uma peça na elucidação da fisiopatogenia da lacaziose, bem como direciona para novas perspectivas terapêuticas com medicamentos imunobiológicos e de biologia sintética. Mais estudos são necessários para elucidar outros fatores que participem na evasão imune do fungo, bem como correlacionar os subtipos clínicos com seus perfis imunológicos de citocinas e fatores de crescimento
Title in English
Immunoexpression of growth factors and cytokines in cutaneous lesions of Jorge Lobo's disease
Keywords in English
Biomarkers
Extracellular Matrix
Immune response antigen
Jorge Lobo's disease
Lobomycosis
Abstract in English
Jorge Lobo's disease is a subcutaneous mycosis that presents clinically as a localized disease, especially in the lower limbs, with a chronic evolution and therapeutic success that is not fully effective. Due to the chronicity of Jorge Lobo's Disease, with the fungus remaining in the tissue for a long period, it is extremely important to activate the host's immune system and, although some studies have already described the pattern of local immune response in both diseases, little is known about the participation and possible role of the interaction of cytokines and growth factors in its pathogenesis. The participation of cytokines and growth factors in the skin lesions of Jorge Lobo's disease was evaluated using immunohistochemical staining, comparing them between the diseases and with the control group. The clinical-demographic characteristics of the investigated patients were also analyzed. Of the 16 patients with Jorge Lobo Disease analyzed, 81.25% were male, 81.25% were aged between 40 and 60 years and the location of the lesions in 43.75% of the cases was on the lower limbs, 25% in the ear, being all patients from Pará State. The increased expression of the markers characterized by the immunostaining was statistically significant and predominant for FGF, TGF- and NGF characterizing an antiinflammatory profile that contributes for immune evasion and fungus survival in spite of being inside an inflammatory environment marked by the also increased TNF-, IL-1 , IL-1 , EGF and PDGF when compared to the control group. This inflammation is inneffective in fungus elimination, but sufficient enough for chronic extracellular matrix remodeling, resulting in the clinical and histopathological features of the disease. This study walks one more step in the direction of elucidating lacaziosis physiopathology and finding new treatment perspectives with immunobiological drugs and synthetic biology. More studies are needed for clarifying other immune evasion factors, as well as correlate clinical subtypes with their cytokines and grow factors profiles
 
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Publishing Date
2024-04-26
 
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