title: Patterns of gene expression in peripheral blood mononuclear cells and outcomes from patients with sepsis secondary to community acquired pneumonia.
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.
authors.affiliation: Center for Experimental Research, Instituto Israelita de Ensino e Pesquisa, Hospital Israelita Albert Einstein, São Paulo, Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Severino
authors.affiliation: Intensive Care Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil.
authors.forename: Eliézer
authors.initials: E
authors.lastname: Silva
authors.affiliation: Division of Infectious Diseases, Hospital São Paulo, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil.
authors.forename: Giovana Lotici
authors.initials: GL
authors.lastname: Baggio-Zappia
authors.affiliation: Division of Infectious Diseases, Hospital São Paulo, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil.
authors.forename: Milena Karina Coló
authors.initials: MK
authors.lastname: Brunialti
authors.affiliation: Division of Infectious Diseases, Hospital São Paulo, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil.
authors.forename: Laura Alejandra
authors.initials: LA
authors.lastname: Nucci
authors.affiliation: Intensive Care Unit, Hospital Sírio Libanês, São Paulo, Brazil.
authors.forename: Otelo
authors.initials: O
authors.lastname: Rigato
authors.affiliation: Department of Gynecology, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil.
authors.forename: Ismael Dale Cotrim Guerreiro
authors.initials: ID
authors.lastname: da Silva
authors.affiliation: Intensive Care Unit, Hospital São Paulo, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil.
authors.forename: Flávia Ribeiro
authors.initials: FR
authors.lastname: Machado
authors.affiliation: Division of Infectious Diseases, Hospital São Paulo, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil.
authors.forename: Reinaldo
authors.initials: R
authors.lastname: Salomao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis*; D016022:Case-Control Studies; D017714:Community-Acquired Infections / Q000150:complications / Q000235:genetics* / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010085:Oxidative Phosphorylation; D011014:Pneumonia / Q000150:complications / Q000235:genetics* / Q000276:immunology; D011379:Prognosis; D018805:Sepsis / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D015415:Biomarkers