Genome-wide expression profiles in very low birth weight infants with neonatal sepsis.
BACKGROUND
Bacterial sepsis is associated with high morbidity and mortality in preterm infants. However, diagnosis of sepsis and identification of the causative agent remains challenging. Our aim was to determine genome-wide expression profiles of very low birth weight (VLBW) infants with and without bacterial sepsis and assess differences.


METHODS
This was a prospective observational double-cohort study conducted in VLBW (<1500 g) infants with culture-positive bacterial sepsis and non-septic matched controls. Blood samples were collected as soon as clinical signs of sepsis were identified and before antibiotics were initiated. Total RNA was processed for genome-wide expression analysis using Affymetrix gene arrays.


RESULTS
During a 19-month period, 17 septic VLBW infants and 19 matched controls were enrolled. First, a three-dimensional unsupervised principal component analysis based on the entire genome (28 000 transcripts) identified 3 clusters of patients based on gene expression patterns: Gram-positive sepsis, Gram-negative sepsis, and noninfected control infants. Furthermore, these groups were confirmed by using analysis of variance, which identified a transcriptional signature of 554 of genes. These genes had a significantly different expression among the groups. Of the 554 identified genes, 66 belonged to the tumor necrosis factor and 56 to cytokine signaling. The most significantly overexpressed pathways in septic neonates related with innate immune and inflammatory responses and were validated by real-time reverse transcription polymerase chain reaction.


CONCLUSIONS
Our preliminary results suggest that genome-wide expression profiles discriminate septic from nonseptic VLBW infants early in the neonatal period. Further studies are needed to confirm these findings.
Health Research Institute (Instituto de Investigación Sanitaria) La Fe, Valencia, Spain; Division of Neonatology, University and Polytechnic Hospital, Valencia, Spain;
María
M
Cernada
Central Research Unit-INCLIVA, Faculty of Medicine, University of Valencia, Spain; and.
Eva
E
Serna
Department of Biotechnology, Instituto de Agroquímica y Tecnología de Alimentos, Consejo Superior de Investigaciones Científicas, Valencia; Spain.
Christine
C
Bauerl
Department of Biotechnology, Instituto de Agroquímica y Tecnología de Alimentos, Consejo Superior de Investigaciones Científicas, Valencia; Spain.
María Carmen
MC
Collado
Department of Biotechnology, Instituto de Agroquímica y Tecnología de Alimentos, Consejo Superior de Investigaciones Científicas, Valencia; Spain.
Gaspar
G
Pérez-Martínez
Health Research Institute (Instituto de Investigación Sanitaria) La Fe, Valencia, Spain; Division of Neonatology, University and Polytechnic Hospital, Valencia, Spain; maximo.vento@uv.es.
Máximo
M
Vento
D001424:Bacterial Infections / Q000175:diagnosis / Q000235:genetics*; D015331:Cohort Studies; D016207:Cytokines / Q000235:genetics; D042241:Early Diagnosis; D005260:Female; D055106:Genome-Wide Association Study; D016905:Gram-Negative Bacterial Infections / Q000175:diagnosis / Q000235:genetics; D016908:Gram-Positive Bacterial Infections / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000175:diagnosis / Q000235:genetics*; D019102:Infant, Very Low Birth Weight; D008297:Male; D025341:Principal Component Analysis; D011446:Prospective Studies; D018805:Sepsis / Q000175:diagnosis / Q000235:genetics*; D015398:Signal Transduction; D059467:Transcriptome / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha
biomarkers; genome-wide expression profile; premature infant; sepsis