Parasite-Derived MicroRNAs in Host Serum As Novel Biomarkers of Helminth Infection

Anna M. Hoy, Rachel J. Lundie, Alasdair C Ivens, Juan F. Quintana, Norman Nausch, Thorsten Forster, Frances Jones, Narcis B. Kabatereine, David W. Dunne, Francisca Mutapi, Andrew S. MacDonald, Amy H. Buck

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79 Citations (Scopus)

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.Methods/Principal Findings: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.

Original languageEnglish
Article numbere2701
Number of pages14
JournalPLoS Neglected Tropical Diseases
Volume8
Issue number2
DOIs
Publication statusPublished - Feb 2014
Externally publishedYes

Cite this

Hoy, Anna M. ; Lundie, Rachel J. ; Ivens, Alasdair C ; Quintana, Juan F. ; Nausch, Norman ; Forster, Thorsten ; Jones, Frances ; Kabatereine, Narcis B. ; Dunne, David W. ; Mutapi, Francisca ; MacDonald, Andrew S. ; Buck, Amy H. / Parasite-Derived MicroRNAs in Host Serum As Novel Biomarkers of Helminth Infection. In: PLoS Neglected Tropical Diseases. 2014 ; Vol. 8, No. 2.
@article{14bab58c661c4f8b8082906dd3d88be9,
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.Methods/Principal Findings: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 na{\"i}ve 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.",
author = "Hoy, {Anna M.} and Lundie, {Rachel J.} and Ivens, {Alasdair C} and Quintana, {Juan F.} and Norman Nausch and Thorsten Forster and Frances Jones and Kabatereine, {Narcis B.} and Dunne, {David W.} and Francisca Mutapi and MacDonald, {Andrew S.} and Buck, {Amy H.}",
year = "2014",
month = "2",
doi = "10.1371/journal.pntd.0002701",
language = "English",
volume = "8",
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Hoy, AM, Lundie, RJ, Ivens, AC, Quintana, JF, Nausch, N, Forster, T, Jones, F, Kabatereine, NB, Dunne, DW, Mutapi, F, MacDonald, AS & Buck, AH 2014, 'Parasite-Derived MicroRNAs in Host Serum As Novel Biomarkers of Helminth Infection', PLoS Neglected Tropical Diseases, vol. 8, no. 2, e2701. https://doi.org/10.1371/journal.pntd.0002701

Parasite-Derived MicroRNAs in Host Serum As Novel Biomarkers of Helminth Infection. / Hoy, Anna M.; Lundie, Rachel J.; Ivens, Alasdair C; Quintana, Juan F.; Nausch, Norman; Forster, Thorsten; Jones, Frances; Kabatereine, Narcis B.; Dunne, David W.; Mutapi, Francisca; MacDonald, Andrew S.; Buck, Amy H.

In: PLoS Neglected Tropical Diseases, Vol. 8, No. 2, e2701, 02.2014.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Parasite-Derived MicroRNAs in Host Serum As Novel Biomarkers of Helminth Infection

AU - Hoy, Anna M.

AU - Lundie, Rachel J.

AU - Ivens, Alasdair C

AU - Quintana, Juan F.

AU - Nausch, Norman

AU - Forster, Thorsten

AU - Jones, Frances

AU - Kabatereine, Narcis B.

AU - Dunne, David W.

AU - Mutapi, Francisca

AU - MacDonald, Andrew S.

AU - Buck, Amy H.

PY - 2014/2

Y1 - 2014/2

N2 - 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.Methods/Principal Findings: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.

AB - 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.Methods/Principal Findings: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.

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U2 - 10.1371/journal.pntd.0002701

DO - 10.1371/journal.pntd.0002701

M3 - Article

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VL - 8

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JF - PLoS Neglected Tropical Diseases

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