• JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
 
  Bookmark and Share
 
 
Master's Dissertation
DOI
https://doi.org/10.11606/D.5.2021.tde-09092021-104352
Document
Author
Full name
Fernando Ramon Zilinski
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2021
Supervisor
Committee
Kokron, Cristina Maria (President)
Marinho, Ana Karolina Barreto Berselli
Perazzio, Sandro Félix
Santos, Keity Souza
Title in Portuguese
Avaliação da expressão e função de PD-1 e seu ligante PD-L1 nas subpopulações de linfócitos B em pacientes com Imunodeficiência Comum Variável (ICV) com manifestações gastr
Keywords in Portuguese
Citometria de Fluxo.
Gastroenteropatias
Imunodeficiência Comum Variável
PD-1 e PD-L1
Subpopulações de Linfócitos B
Abstract in Portuguese
Introdução: A Imunodeficiência Comum Variável (ICV) é uma imunodeficiência primária caracterizada por hipogamaglobulinemia, infecções de repetição, predisposição a doenças autoimunes, inflamatórias e câncer, deficiência de produção de anticorpos específicos decorrentes de distúrbios na diferenciação das linfócitos B (LB) em plasmócitos e células B de memória. As manifestações gastrointestinais estão presentes em 20 a 60% dos pacientes com ICV. Estudos recentes mostram que a via PD-1/PD-L1 pode ter importância na resposta humoral, principalmente durante a sinalização entre linfócitos TFH e linfócitos B, sendo que, quando alterada, pode levar a diminuição das células plasmáticas de vida longa e produção de anticorpos. Hipotetizamos que a expressão da molécula PD-1 e de seu ligante PD-L1 nas diferentes subpopulações de linfócitos B de pacientes com ICV com doença gastrointestinal (ICV-GI) estaria alterada, interferindo na maturação dos plasmoblastos (PBL), que estão diminuídos nestes pacientes. Objetivos: avaliar a expressão destas moléculas nas subpopulações de LB dos pacientes com ICV-GI, buscando correlacionar com as diferentes manifestações clínicas e imunológicas relacionadas à doença. Coorte e Métodos: Foram coletadas amostras de sangue periférico de 43 pacientes portadores de ICV, sendo 29 com ICV-GI e 14 com apenas infecções de repetição, além de 24 controles saudáveis. Avaliamos a expressão das moléculas PD-1 e PD-L1 nas diferentes subpopulações de LB por citometria de fluxo. Resultados: Pacientes com ICV-GI apresentaram frequência reduzida de linfócitos B, aumento de LB transicionais e de LB naïve, redução de LB de memória sem troca de isotipo, LB de memória com troca de isotipo e também de plasmócitos quando comparados aos controles. Comparado ao grupo de pacientes com ICV sem complicações, apenas a frequência de LB transicionais foi significativamente maior. A expressão de PD-1 em LB totais e LB transicionais de pacientes com ICV-GI está reduzida, não se observando diferença nos outros subtipos de LB quando comparados aos controles. Não houve diferença na expressão de PD-1 entre os 2 grupos de pacientes com ICV. Conclusões: A expressão de PD-1 e PD-L1 em pacientes com ICV não se mostrou expressivamente diferente da observada em controles sugerindo que esta via não parece causar um bloqueio na maturação dos LB, entretanto, mais estudos são necessários para entender como essa via se comporta nos LB desses pacientes
Title in English
Evaluation of the expression and function of PD-1 and its ligand PD-L1 in subpopulations of B lymphocytes in patients with Common Variable Immunodeficiency (CVID) with gastrointestinal manifestations
Keywords in English
B Lymphocyte Subpopulation
Common Variable Immunodeficiency (CVID)
Flow Cytometry
Gastrointestinal diseases
PD-1 and PD-L1
Abstract in English
Introduction: Common Variable Immunodeficiency (CVID) is a primary immunodeficiency characterized by hypogammaglobulinemia, recurrent infections, predisposition to autoimmune and inflammatory diseases and cancer, deficiency in the production of specific antibodies resulting from disturbances in the differentiation of B lymphocytes (LB) into plasma cells and memory B cells. Gastrointestinal manifestations are present in 20 to 60% of patients with CVID. Recent studies show that the PD-1 / PD-L1 pathway may be important in the humoral response, especially during signaling between TFH and B lymphocytes, and when altered, it can lead to a decrease in long-lived plasma cells and production of antibodies. We hypothesized that the expression of the PD-1 molecule and its ligand PD-L1 in the different subpopulations of B lymphocytes of patients with CVID with gastrointestinal disease (CVID-GI) would be altered, interfering in the maturation of plasmoblasts (PBL), which are decreased in these patients. Objectives: to evaluate the expression of these molecules in LB subpopulations of patients with CVID-GI, looking to correlate with the different clinical and immunological manifestations related to the disease. Cohort and Methods: Peripheral blood samples were collected from 43 patients with ICV, 29 with CVID-GI and 14 with only recurrent infections, in addition to 24 healthy controls. We evaluated the expression of the PD-1 and PD-L1 molecules in different LB subpopulations by flow cytometry. Results: Patients with CVID-GI showed a reduced frequency of B lymphocytes, an increase in transitional B cells and naïve B cells, a reduction in unswitched memory B cells, switched memory B cells and also in plasmoblasts cells when compared to controls. Compared to the group of patients with infections only CVID, only the frequency of transitional B cells was significantly higher. The expression of PD-1 in total B cells and transitional B cells in patients with CVID-GI is reduced, with no difference being observed in the other B lymphocytes subtypes when compared to HC. There was no difference in the expression of PD-1 between the 2 groups of patients with CVID. Conclusions: The expression of PD-1 and PD-L1 in patients with CVID was not significantly different from that observed in HC, suggesting that this pathway does not seem to cause a block in the maturation of B cells, however, further studies are needed to understand how this pathway behaves in the B cells of these patients.
 
WARNING - Viewing this document is conditioned on your acceptance of the following terms of use:
This document is only for private use for research and teaching activities. Reproduction for commercial use is forbidden. This rights cover the whole data about this document as well as its contents. Any uses or copies of this document in whole or in part must include the author's name.
Publishing Date
2021-09-09
 
WARNING: Learn what derived works are clicking here.
All rights of the thesis/dissertation are from the authors
CeTI-SC/STI
Digital Library of Theses and Dissertations of USP. Copyright © 2001-2021. All rights reserved.