title: Parasite-derived microRNAs in host serum as novel biomarkers of helminth infection.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are a class of short non-coding RNA that play important roles in disease processes in animals and are present in a highly stable cell-free form in body fluids. Here, we examine the capacity of host and parasite miRNAs to serve as tissue or serum biomarkers of Schistosoma mansoni infection.
  
  
  RESULTS
  We used Exiqon miRNA microarrays to profile miRNA expression in the livers of mice infected with S. mansoni at 7 weeks post-infection. Thirty-three mouse miRNAs were differentially expressed in infected compared to naïve mice (>2 fold change, p<0.05) including miR-199a-3p, miR-199a-5p, miR-214 and miR-21, which have previously been associated with liver fibrosis in other settings. Five of the mouse miRNAs were also significantly elevated in serum by twelve weeks post-infection. Sequencing of small RNAs from serum confirmed the presence of these miRNAs and further revealed eleven parasite-derived miRNAs that were detectable by eight weeks post infection. Analysis of host and parasite miRNA abundance by qRT-PCR was extended to serum of patients from low and high infection sites in Zimbabwe and Uganda. The host-derived miRNAs failed to distinguish uninfected from infected individuals. However, analysis of three of the parasite-derived miRNAs (miR-277, miR-3479-3p and bantam) could detect infected individuals from low and high infection intensity sites with specificity/sensitivity values of 89%/80% and 80%/90%, respectively.
  
  
  CONCLUSIONS
  This work identifies parasite-derived miRNAs as novel markers of S. mansoni infection in both mice and humans, with the potential to be used with existing techniques to improve S. mansoni diagnosis. In contrast, although host miRNAs are differentially expressed in the liver during infection their abundance levels in serum are variable in human patients and may be useful in cases of extreme pathology but likely hold limited value for detecting prevalence of infection.
authors.affiliation: Centre for Immunity, Infection and Evolution, Ashworth Laboratories, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Hoy
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Lundie
authors.affiliation: Centre for Immunity, Infection and Evolution, Ashworth Laboratories, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Alasdair
authors.initials: A
authors.lastname: Ivens
authors.affiliation: Centre for Immunity, Infection and Evolution, Ashworth Laboratories, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Quintana
authors.affiliation: Centre for Immunity, Infection and Evolution, Ashworth Laboratories, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Norman
authors.initials: N
authors.lastname: Nausch
authors.affiliation: Division of Pathway Medicine, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Forster
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Frances
authors.initials: F
authors.lastname: Jones
authors.affiliation: Vector Control Division, Ministry of Health, Kampala, Uganda.
authors.forename: Narcis B
authors.initials: NB
authors.lastname: Kabatereine
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: David W
authors.initials: DW
authors.lastname: Dunne
authors.affiliation: Centre for Immunity, Infection and Evolution, Ashworth Laboratories, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Francisca
authors.initials: F
authors.lastname: Mutapi
authors.affiliation: Centre for Immunity, Infection and Evolution, Ashworth Laboratories, University of Edinburgh, Edinburgh, United Kingdom ; Manchester Collaborative Centre for Inflammation Research, The University of Manchester, Manchester, United Kingdom.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Macdonald
authors.affiliation: Centre for Immunity, Infection and Evolution, Ashworth Laboratories, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Amy H
authors.initials: AH
authors.lastname: Buck
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008099:Liver / Q000469:parasitology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D008875:Middle Aged; D018510:RNA, Helminth / Q000097:blood*; D012550:Schistosoma mansoni / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D012555:Schistosomiasis mansoni / Q000097:blood* / Q000453:epidemiology / Q000469:parasitology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D018510:RNA, Helminth