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Doctoral Thesis
DOI
10.11606/T.5.2019.tde-13022019-145705
Document
Author
Full name
Frederico José Silva Correa
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2018
Supervisor
Committee
Abrão, Mauricio Simões (President)
Schor, Eduardo
Melo, Nilson Roberto de
Podgaec, Sérgio
Title in Portuguese
Avaliação das células iNKT em pacientes com endometriose
Keywords in Portuguese
Células T matadoras naturais
Citometria de fluxo
Dor pélvica
Endometriose
Interleucinas
Microscopia confocal
Abstract in Portuguese
Introdução: A endometriose é uma doença com características inflamatórias que atinge as mulheres em idade reprodutiva. A patogênese da endometriose não está esclarecida. Tem sido demonstrada associação entre distúrbios imunológicos e endometriose, como alterações nos macrófagos, células NK, citocinas e nas repostas Th1, Th2 e Th17. As células iNKT, um tipo especial de linfócitos T, tem importante papel na resposta inflamatória como mediadores das repostas Th1, Th2 e Th17. Objetivos: o objetivo principal deste estudo foi comparar as frequências das células iNKT e seus subtipos entre pacientes com endometriose e pacientes sem endometriose. Procuramos também comparar as frequências destas células em ambos os grupos relacionando com alguns os aspectos clínicos e cirúrgicos da doença. Métodos: Realizamos estudo transversal, prospectivo entre fevereiro de 2013 a fevereiro de 2015 que avaliou a porcentagem de células iNKT e os subtipos iNKT CD4+, iNKT CD4+ CCR7+, iNKT CD4+ CD25+, iNKT DN, iNKT DN CCR7+, iNKT DN CD25+, iNKT CD4+ IL6+, iNKT CD4+ IL10+, iNKT CD4+ IL17+, iNKT CD8+ IL6+, iNKT CD8+ IL10+, iNKT CD8+ IL17+, iNKT DN IL6+, iNKT DN IL10+, iNKT DN IL17+ no sangue periférico, por citometria de fluxo, em pacientes com endometriose profunda (n = 47) e sem endometriose (n = 26). As frequências de células iNKT e seus subtipos foram comparadas entre os grupos de acordo com os sintomas, fase do ciclo, estádio da doença e classificação histológica. Resultados: Na avaliação da frequência das células iNKT, iNKT DN e iNKT DN IL17+ foi evidenciada diminuição significativa nas pacientes com endometriose (p=0,010, p=0,020, p=0,050; respectivamente). Além disso, foi observada diminuição significativa nas frequências das células iNKT CD4+ CCR7+ e aumento significativo das células iNKT CD4+ IL-17+ em pacientes com endometriose e dismenorréia severa em comparação a dismenorréia ausente/leve. Nas pacientes com endometriose e dor acíclica severa observou-se diminuição significativa da frequência das células iNKT CD4+ IL17+ em comparação a dor acíclica ausente/leve (p=0,048). Houve diminuição das células iNKT nas pacientes com endometriose em relação ao grupo controle na fase secretora do ciclo menstrual (p=0,030). Na avaliação da fase do ciclo menstrual foi observado na fase proliferativa aumento significativo na frequência das células iNKT CD4+ CD25+ (p=0,022) e diminuição significativa das células iNKT DN (p=0,011) nas pacientes com endometriose. Na fase secretora foi evidenciado diminuição significativa na frequência das células iNKT DN IL17+ (p=0,049) nas pacientes com endometriose. Foi identificado também nas pacientes com endometriose uma diminuição na frequência das células iNKT DN CD25+ na fase secretora em relação a fase proliferativa do ciclo menstrual. Conclusões: As células iNKT e os subtipos iNKT DN e iNKT DN IL17+ se mostraram alteradas nas pacientes com endometriose profunda. Subtipos específicos de células iNKT estão alteradas nas pacientes com endometriose profunda em pacientes com dismenorréia e dor acíclica severas. As fases do ciclo menstrual estão relacionadas a alteração nas frequências das células iNKT e dos subtipos iNKT CD4+ CD25+, iNKT DN, iNKT DN IL17+ e iNKT DN CD25+ nas pacientes com endometriose profunda. Estes resultados sugerem participação das células iNKT no desenvolvimento da endometriose
Title in English
Evaluation of iNKT cells in patients with endometriosis
Keywords in English
Endometriosis
Flow cytometry
Interleukins
Microscopy confocal
Natural killer T-cells
Pelvic pain
Abstract in English
Introduction: Endometriosis is a disease with inflammatory characteristics that affects women of reproductive age. The pathogenesis of endometriosis is unclear. There has been an association between immune disorders and endometriosis, such as changes in macrophages, NK cells, cytokines, and Th1, Th2 and Th17 responses. iNKT cells, a special type of T lymphocytes, play an important role in the inflammatory response as mediators of the Th1, Th2 and Th17 responses. Objectives: The main objective of this study was to compare the frequencies of iNKT cells and their subtypes between patients with endometriosis and patients without endometriosis. We also compare the frequencies of these cells in both groups relating to some clinical and surgical aspects of the disease. Methods: We performed a prospective cross-sectional study between February 2013 and February 2015, which evaluated the percentage of iNKT cells and iNKT CD4+, iNKT CD4+ CCR7+, iNKT CD4+ CD25+, iNKT DN, iNKT DN CCR7+, iNKT DN CD25+, iNKT CD4+ IL6+ , iNKT CD8+ IL17+, iNKT DN IL6+, iNKT DN IL10+, iNKT DN IL17+ in the peripheral blood, by flow cytometry, in patients with deep endometriosis (n = 47), iNKT CD4+ IL10+, iNKT CD4+ IL17+, iNKT CD8+ ) and without endometriosis (n = 26). The frequencies of iNKT cells and their subtypes were compared between groups according to symptoms, stage of the cycle, stage of the disease and histological classification. Results: iNKT, iNKT DN and iNKT DN IL17+ cells showed significant decrease in patients with endometriosis (p = 0.010, p = 0.020, p = 0.050, respectively). In addition, a significant decrease in iNKT CD4+ CCR7+ cell numbers and a significant increase of iNKT CD4+ IL17+ cells were observed in patients with endometriosis and severe dysmenorrhea compared to absent / mild dysmenorrhea. In patients with endometriosis and severe acyclic pain, there was a significant decrease in the frequency of iNKT CD4+ IL17+ cells compared to absent / mild acyclic pain (p = 0.048). There was a decrease in iNKT cells in patients with endometriosis compared to the control group in the secretory phase of the menstrual cycle (p = 0.030). In the menstrual cycle, a significant increase in iNKT CD4+ CD25+ cells (p = 0.022) and a significant decrease in iNKT DN cells (p = 0.011) was observed in the proliferative phase in patients with endometriosis. In the secretory phase there was a significant decrease in the frequency of iNKT DN IL17 + cells (p = 0.049) in patients with endometriosis. It was also identified in patients with endometriosis a decrease in the frequency of iNKT DN CD25+ cells in the secretory phase in relation to the proliferative phase of the menstrual cycle. Conclusions: iNKT cells and subtypes iNKT DN e iNKT DN IL17+ have been altered in patients with deep endometriosis. Specific subtypes of iNKT cells are altered in patients with deep endometriosis in patients with severe dysmenorrhea and acyclic pain. The phases of the menstrual cycle are related to changes in the frequencies of iNKT cells and subtypes iNKT CD4+ CD25+, iNKT DN, iNKT DN IL17+ and iNKT DN CD25+ in patients with deep endometriosis. These results suggest the participation of iNKT cells in the development of endometriosis
 
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Publishing Date
2019-02-14
 
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