title: Evaluation of mRNA Biomarkers to Identify Risk of Hospital Acquired Infections in Children Admitted to Paediatric Intensive Care Unit.
abstract: OBJECTIVE
  Hospital-acquired infections (HAI) are associated with significant mortality and morbidity and prolongation of hospital stay, adding strain on limited hospital resources. Despite stringent infection control practices some children remain at high risk of developing HAI. The development of biomarkers which could identify these patients would be useful. In this study our objective was to evaluate mRNA candidate biomarkers for HAI prediction in a pediatric intensive care unit.
  
  
  METHODS
  Serial blood samples were collected from patients admitted to pediatric intensive care unit between March and June 2012. Candidate gene expression (IL1B, TNF, IL10, CD3D, BCL2, BID) was quantified using RT-qPCR. Comparisons of relative gene expression between those that did not develop HAI versus those that did were performed using Mann Whitney U-test.
  
  
  METHODS
  Exclusion criteria were: age <28 days or ≥16 years, expected length of stay < 24 hours, expected survival < 28 days, end-stage renal disease and end-stage liver disease. Finally, 45 children were included in this study.
  
  
  RESULTS
  The overall HAI rate was 30% of which 62% were respiratory infections. Children who developed HAI had a three-fold increase in hospital stay compared to those who did not (27 days versus 9 days, p<0.001). An increased expression of cytokine genes (IL1B and IL10) was observed in patients who developed HAI, as well as a pro-apoptosis pattern (higher expression of BID and lower expression of BCL2). CD3D, a key TCR co-factor was also significantly down-modulated in patients who developed HAI.
  
  
  CONCLUSIONS
  To our knowledge, this is the first study of mRNA biomarkers of HAI in the paediatric population. Increased mRNA expressions of anti-inflammatory cytokine and modulation of apoptotic genes suggest the development of immunosuppression in critically ill children. Immune monitoring using a panel of genes may offer a novel stratification tool to identify HAI risk.
authors.affiliation: Joint Research Unit Hospices Civils de Lyon / bioMérieux, Hôpital Edouard Herriot-Pathophysiology of injury induced immunosuppression (PI3) Lab, Lyon 1 University / Hospices Civils de Lyon / bioMérieux, Lyon, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Peronnet
authors.affiliation: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Kha
authors.initials: K
authors.lastname: Nguyen
authors.affiliation: Joint Research Unit Hospices Civils de Lyon / bioMérieux, Hôpital Edouard Herriot-Pathophysiology of injury induced immunosuppression (PI3) Lab, Lyon 1 University / Hospices Civils de Lyon / bioMérieux, Lyon, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Cerrato
authors.affiliation: Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Rathi
authors.initials: R
authors.lastname: Guhadasan
authors.affiliation: Joint Research Unit Hospices Civils de Lyon / bioMérieux, Hôpital Edouard Herriot-Pathophysiology of injury induced immunosuppression (PI3) Lab, Lyon 1 University / Hospices Civils de Lyon / bioMérieux, Lyon, France.|Immunology Laboratory, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Venet
authors.affiliation: Joint Research Unit Hospices Civils de Lyon / bioMérieux, Hôpital Edouard Herriot-Pathophysiology of injury induced immunosuppression (PI3) Lab, Lyon 1 University / Hospices Civils de Lyon / bioMérieux, Lyon, France.|Anesthesiology and Intensive Care department, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Textoris
authors.affiliation: Joint Research Unit Hospices Civils de Lyon / bioMérieux, Hôpital Edouard Herriot-Pathophysiology of injury induced immunosuppression (PI3) Lab, Lyon 1 University / Hospices Civils de Lyon / bioMérieux, Lyon, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pachot
authors.affiliation: Joint Research Unit Hospices Civils de Lyon / bioMérieux, Hôpital Edouard Herriot-Pathophysiology of injury induced immunosuppression (PI3) Lab, Lyon 1 University / Hospices Civils de Lyon / bioMérieux, Lyon, France.|Immunology Laboratory, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Monneret
authors.affiliation: Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Enitan Delphine
authors.initials: ED
authors.lastname: Carrol
mesh_terms: D000293:Adolescent; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D017252:CD3 Complex / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D003140:Communicable Disease Control; D003428:Cross Infection / Q000175:diagnosis* / Q000382:microbiology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation; D015278:Intensive Care Units, Pediatric; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007902:Length of Stay; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011786:Quality Control; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: C000595707:BCL2 protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D015415:Biomarkers; D017252:CD3 Complex; D016207:Cytokines; C508609:IL10 protein, human; C508585:IL1B protein, human; D053583:Interleukin-1beta; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016753:Interleukin-10