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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2017.tde-27092017-154334
Document
Author
Full name
Tábata Takahashi França
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Condino Neto, Antonio (President)
Cavinato, Regiane Aparecida
Kokron, Cristina Maria
Negro, Sonia Jancar
Title in Portuguese
Avaliação da formação de NETs em pacientes com deficiência de CD40 ligante.
Keywords in Portuguese
Deficiência de CD40L
IFN-
NETs
Neutrófilos
X-HIGM
Abstract in Portuguese
Estudos recentes demonstraram que as armadilhas extracelulares de neutrófilos (NETs) formam uma estrutura capaz de anular fatores de virulência e destruir microrganismos. Pacientes portadores da síndrome de Hiper-IgM ligada ao X (X-HIGM), imunodeficiência causada por mutações no gene do CD40 ligante (CD40L), são altamente suscetíveis a infecções oportunistas causadas por fungos. Uma vez que a resposta de neutrófilos apresenta grande importância para o controle de infecções fúngicas e estudos que apontam influencia da interação CD40-CD40L na granulopoiese, propusemos investigar se a suscetibilidade a infecções em pacientes com X-HIGM estariam relacionadas à falha na formação de NETs. Os resultados obtidos indicam que pacientes X-HIGM apresentam falha na geração de NETs de maneira estímulo-dependente, possivelmente relacionada a maturação incompleta dos neutrófilos. O estudo contribui para o avanço no conhecimento sobre a imunopatologia da deficiência de CD40L e para elucidação dos mecanismos envolvidos na suscetibilidade a infecções em pacientes com X-HIGM.
Title in English
Evaluation of NET formation in CD40 ligand deficient patients.
Keywords in English
CD40L deficiency
IFN-
NETs
Neutrophils
X-HIGM
Abstract in English
Recent studies have shown that neutrophil extracellular traps (NETs) release an structure able to annul virulence factors and destroying microorganisms. Patients with X-linked Hyper-IgM syndrome (X-HIGM), a rare immunodeficiency caused by mutations in the CD40 ligand (CD40L) gene, are highly susceptible to opportunistic infections caused by fungi. Since neutrophil responses are important to control fungal infection and studies that indicate the influence of CD40-CD40L interaction on granulopoiesis, we propose to investigate whether the susceptibility to infections in X-HIGM patients could be related to the failure in NET formation. The results indicate that X-HIGM patients present a failure in NET generation in a stimulus-dependent manner, likely related to incomplete neutrophil maturation. The study contributes to the advancement of knowledge on the immunopathology of CD40L deficiency and contributes to elucidate the mechanisms involved in the susceptibility to infections in X-HIGM patients.
 
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Publishing Date
2017-09-27
 
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