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

Author 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
Institution Hosp Israelita Albert Einstein
Universidade Federal de São Paulo (UNIFESP)
Hosp Sirio Libanes
Abstract 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.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Albert Einstein Research and Education Institute - Hospital Israelita Albert Einstein
Grant number FAPESP: FAPESP 2006/58744-1
Date 2014-03-25
Published in Plos One. San Francisco: Public Library Science, v. 9, n. 3, 8 p., 2014.
ISSN 1932-6203 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent 8
Origin http://dx.doi.org/10.1371/journal.pone.0091886
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000333675600014
URI http://repositorio.unifesp.br/handle/11600/37557

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