title: Decreased pattern recognition receptor signaling, interferon-signature, and bactericidal/permeability-increasing protein gene expression in cord blood of term low birth weight human newborns.
abstract: BACKGROUND
  Morbidity and mortality rates of low birth weight (LBW) newborns at term are higher than rates in normal birth weight (NBW) newborns. LBW newborns are at greater risk to acquire recurrent bacterial and viral infections during their first few weeks of life possibly as an outcome of compromised innate immune functions. As adaptive immunity is in a naive state, increased risk of infection of LBW as compared to NBW newborns may reflect impairments in innate immunity.
  
  
  METHODS
  To characterize the increased susceptibility to infections in LBW newborns we used microarray technology to identify differences in gene expression in LBW newborns (n = 8) compared to NBW newborns (n = 4) using cord blood. The results obtained from the microarray study were validated on a larger number of samples using real time RT-PCR (LBW = 22, NBW = 18) and western blotting (LBW = 12, NBW = 12). The Interferome database was used to identify interferon (IFN) signature genes and ingenuity pathway analysis identified canonical pathways and biological functions associated with the differentially expressed genes in LBW newborns. ELISAs for IFNs and bactericidal/permeability-increasing protein were performed in both LBW and NBW newborns and in adults (LBW = 18, NBW = 18, Adults= 8).
  
  
  RESULTS
  Upon microarray analysis, we identified 1,391 differentially expressed genes, of which, 1,065 genes were down-regulated and 326 genes were up-regulated in the LBW compared to NBW newborns. Of note, 70 IFN-signature genes were found to be significantly down-regulated in LBW compared to NBW newborns. Ingenuity pathway analysis revealed pattern recognition receptors signaling including Toll-Like Receptors (TLRs) -1, -5, and -8 genes and IFN signaling as the most significantly impacted pathways. Respiratory infectious diseases were the most significantly affected bio-functions in LBW newborns.
  
  
  CONCLUSIONS
  Diminished PRRs, IFN-signature, and BPI gene expression raises the possibility that impairments in these pathways contribute to the susceptibility of LBW term infants to infection.
authors.affiliation: Department of Molecular and Human Genetics, Faculty of Science, Banaras Hindu University, Varanasi, India.
authors.forename: Vikas Vikram
authors.initials: VV
authors.lastname: Singh
authors.forename: Sudhir Kumar
authors.initials: SK
authors.lastname: Chauhan
authors.forename: Richa
authors.initials: R
authors.lastname: Rai
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
authors.forename: Shiva M
authors.initials: SM
authors.lastname: Singh
authors.forename: Geeta
authors.initials: G
authors.lastname: Rai
mesh_terms: D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000378:metabolism; D001798:Blood Proteins / Q000235:genetics* / Q000378:metabolism; D016000:Cluster Analysis; D003141:Communicable Diseases / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000821:virology; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D005312:Fetal Blood / Q000378:metabolism* / Q000382:microbiology / Q000821:virology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007230:Infant, Low Birth Weight / Q000502:physiology*; D007231:Infant, Newborn; D007372:Interferons / Q000235:genetics* / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000378:metabolism*; D015203:Reproducibility of Results; D012140:Respiratory Tract Diseases / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000821:virology; D015398:Signal Transduction; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000378:metabolism; D051200:Toll-Like Receptor 8 / Q000235:genetics / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D015852:Eukaryotic Initiation Factor-2; D051192:Receptors, Pattern Recognition; D051198:Toll-Like Receptor 5; D051200:Toll-Like Receptor 8; C021623:bactericidal permeability increasing protein; D007372:Interferons