Patterns of Gene Expression in Peripheral Blood Mononuclear Cells and Outcomes from Patients with Sepsis Secondary to Community Acquired Pneumonia

Patterns of Gene Expression in Peripheral Blood Mononuclear Cells and Outcomes from Patients with Sepsis Secondary to Community Acquired Pneumonia

Autor Severino, Patricia Google Scholar
Silva, Eliezer Google Scholar
Baggio-Zappia, Giovana Lotici Autor UNIFESP Google Scholar
Brunialti, Milena Karina Coló Autor UNIFESP Google Scholar
Nucci, Laura Alejandra Autor UNIFESP Google Scholar
Rigato, Otelo Google Scholar
Silva, Ismael Dale Cotrim Guerreiro da Autor UNIFESP Google Scholar
Machado, Flavia Ribeiro Autor UNIFESP Google Scholar
Salomao, Reinaldo Autor UNIFESP Google Scholar
Instituição Hosp Israelita Albert Einstein
Universidade Federal de São Paulo (UNIFESP)
Hosp Sirio Libanes
Resumo Mechanisms governing the inflammatory response during sepsis have been shown to be complex, involving cross-talk between diverse signaling pathways. Current knowledge regarding the mechanisms underlying sepsis provides an incomplete picture of the syndrome, justifying additional efforts to understand this condition. Microarray-based expression profiling is a powerful approach for the investigation of complex clinical conditions such as sepsis. in this study, we investigate whole-genome expression profiles in mononuclear cells from survivors (n = 5) and non-survivors (n = 5) of sepsis. To circumvent the heterogeneity of septic patients, only patients admitted with sepsis caused by community-acquired pneumonia were included. Blood samples were collected at the time of sepsis diagnosis and seven days later to evaluate the role of biological processes or genes possibly involved in patient recovery. Principal Components Analysis (PCA) profiling discriminated between patients with early sepsis and healthy individuals. Genes with differential expression were grouped according to Gene Ontology, and most genes related to immune defense were up-regulated in septic patients. Additionally, PCA in the early stage was able to distinguish survivors from non-survivors. Differences in oxidative phosphorylation seem to be associated with clinical outcome because significant differences in the expression profile of genes related to mitochondrial electron transport chain (ETC) I-V were observed between survivors and non-survivors at the time of patient enrollment. Global gene expression profiles after seven days of sepsis progression seem to reproduce, to a certain extent, patterns collected at the time of diagnosis. Gene expression profiles comparing admission and follow-up samples differed between survivors and non-survivors, with decreased expression of genes related to immune functions in non-survivors. in conclusion, genes related to host defense and inflammatory response ontology were up-regulated during sepsis, consistent with the need for a host response to infection, and the sustainability of their expression in follow-up samples was associated with outcomes.
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Albert Einstein Research and Education Institute - Hospital Israelita Albert Einstein
Número do financiamento FAPESP: FAPESP 2006/58744-1
Data de publicação 2014-03-25
Publicado em Plos One. San Francisco: Public Library Science, v. 9, n. 3, 8 p., 2014.
ISSN 1932-6203 (Sherpa/Romeo, fator de impacto)
Publicador Public Library Science
Extensão 8
Fonte http://dx.doi.org/10.1371/journal.pone.0091886
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000333675600014
Endereço permanente http://repositorio.unifesp.br/handle/11600/37557

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