title: Gene expression profiling at birth characterizing the preterm infant with early onset infection.
abstract: Early onset infection (EOI) in preterm infants <32 weeks gestational age (GA) is associated with a high mortality rate and the development of severe acute and long-term complications. The pathophysiology of EOI is not fully understood and clinical and laboratory signs of early onset infections in this patient cohort are often not conclusive. Thus, the aim of this study was to identify signatures characterizing preterm infants with EOI by using genome-wide gene expression (GWGE) analyses from umbilical arterial blood of preterm infants. This prospective cohort study was conducted in preterm infants <32 weeks GA. GWGE analyses using CodeLink human microarrays were performed from umbilical arterial blood of preterm infants with and without EOI. GWGE analyses revealed differential expression of 292 genes in preterm infants with EOI as compared to infants without EOI. Infants with EOI could be further differentiated into two subclasses and were distinguished by the magnitude of the expression of genes involved in both neutrophil and T cell activation. A hallmark activity for both subclasses of EOI was a common suppression of genes involved in natural killer (NK) cell function, which was independent from NK cell numbers. Significant results were recapitulated in an independent validation cohort. Gene expression profiling may enable early and more precise diagnosis of EOI in preterm infants.
  
  
  
  Gene expression (GE) profiling at birth characterizes preterm infants with EOI. GE analysis indicates dysregulation of NK cell activity. NK cell activity at birth may be a useful marker to improve early diagnosis of EOI.
authors: Department of Neonatology, Grosshadern, Ludwig-Maximilian University Munich, Germany and the Comprehensive Pneumology Center, Helmholtz Zentrum Muenchen, Munich, Germany, Member of the German Center for Lung Research (DZL), Munich, Germany.|Department of Pediatrics and Neonatology, Justus-Liebig University Giessen, Germany, Member of the German Center for Lung Research (DZL), Giessen, Germany.
authors: Anne
authors: A
authors: Hilgendorff
authors: Institute for Medical Microbiology, Justus-Liebig University Giessen, Member of the German Center for Infection Research (DZIF), Schubertstr. 81, 35392, Giessen, Germany.|Institute for Medical Informatics, Justus-Liebig-University Giessen, Giessen, Germany.
authors: Anita
authors: A
authors: Windhorst
authors: Hospital Barmherzige Brueder, Regensburg, Germany.
authors: Manuel
authors: M
authors: Klein
authors: Institute for Medical Microbiology, Justus-Liebig University Giessen, Member of the German Center for Infection Research (DZIF), Schubertstr. 81, 35392, Giessen, Germany.
authors: Svetlin
authors: S
authors: Tchatalbachev
authors: Institute of Medical Biometry and Epidemiology, Philipps-University Marburg, Marburg, Germany.
authors: Christine
authors: C
authors: Windemuth-Kieselbach
authors: Department of Pediatrics and Neonatology, Justus-Liebig University Giessen, Germany, Member of the German Center for Lung Research (DZL), Giessen, Germany.
authors: Joachim
authors: J
authors: Kreuder
authors: Department of Neonatology and Pediatric Intensive Care, University Medicine, Greifswald, Germany.
authors: Matthias
authors: M
authors: Heckmann
authors: Department of Pediatrics and Neonatology, Justus-Liebig University Giessen, Germany, Member of the German Center for Lung Research (DZL), Giessen, Germany.
authors: Anna
authors: A
authors: Gkatzoflia
authors: Department of Pediatrics and Neonatology, Justus-Liebig University Giessen, Germany, Member of the German Center for Lung Research (DZL), Giessen, Germany.
authors: Harald
authors: H
authors: Ehrhardt
authors: Institute for Molecular Immunology, Helmholtz Center Munich, Munich, Germany.
authors: Josef
authors: J
authors: Mysliwietz
authors: Institute for Medical Microbiology, Justus-Liebig University Giessen, Member of the German Center for Infection Research (DZIF), Schubertstr. 81, 35392, Giessen, Germany.
authors: Michael
authors: M
authors: Maier
authors: Institute for Medical Microbiology, Justus-Liebig University Giessen, Member of the German Center for Infection Research (DZIF), Schubertstr. 81, 35392, Giessen, Germany.|Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors: Benjamin
authors: B
authors: Izar
authors: Institute for Medical Microbiology, Justus-Liebig University Giessen, Member of the German Center for Infection Research (DZIF), Schubertstr. 81, 35392, Giessen, Germany.
authors: Andre
authors: A
authors: Billion
authors: Department of Pediatrics and Neonatology, University of Saarland, Homburg, Germany.
authors: Ludwig
authors: L
authors: Gortner
authors: Institute for Medical Microbiology, Justus-Liebig University Giessen, Member of the German Center for Infection Research (DZIF), Schubertstr. 81, 35392, Giessen, Germany.
authors: Trinad
authors: T
authors: Chakraborty
authors: Institute for Medical Microbiology, Justus-Liebig University Giessen, Member of the German Center for Infection Research (DZIF), Schubertstr. 81, 35392, Giessen, Germany. Hamid.M.Hossain@mikrobio.med.uni-giessen.de.
authors: Hamid
authors: H
authors: Hossain
mesh_terms: D017668:Age of Onset; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D042241:Early Diagnosis; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000175:diagnosis* / Q000235:genetics; D007239:Infections / Q000175:diagnosis* / Q000235:genetics; D007694:Killer Cells, Natural / Q000378:metabolism; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000235:genetics; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000235:genetics; D009504:Neutrophils / Q000378:metabolism; D011446:Prospective Studies; D012313:RNA / Q000097:blood; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; C075005:GNLY protein, human; C527059:KLRC2 protein, human; C497869:KLRD1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D012313:RNA
keywords: Gene expression profiling; Neonatal sepsis