Differential plasma microRNA profiles in HBeAg positive and HBeAg negative children with chronic hepatitis B

Thilde Nordmann Winther; Claus Heiner Bang-Berthelsen; Ida Louise Heiberg; Flemming Pociot; Birthe Hogh

doi:10.1371/journal.pone.0058236

Differential plasma microRNA profiles in HBeAg positive and HBeAg negative children with chronic hepatitis B

Thilde Nordmann Winther, Claus Heiner Bang-Berthelsen, Ida Louise Heiberg, Flemming Pociot, Birthe Hogh

43 Citationer (Scopus)

Abstract

Background and Aim: Children chronically infected with hepatitis B virus (HBV) are at high risk of progressive liver disease. However, no treatment is available that is consistently effective in curing chronic hepatitis B (CHB) in children. Improved understanding of the natural course of disease is warranted. Identification of specific microRNA (miRNA) profiles in children chronically infected with HBV may provide insight into the pathogenesis of CHB and lead to advances in the management of children with CHB. Patients and Methods: MiRNA PCR panels were employed to screen plasma levels of 739 miRNAs in pooled samples from HBeAg positive, HBeAg negative, and healthy children. The three groups' plasma miRNA profiles were compared, and aberrantly expressed miRNAs were identified. The identified miRNAs were then validated. Individual RT-qPCRs were performed on plasma from 34 HBeAg positive, 26 HBeAg negative, and 60 healthy children. Results: A panel of 16 plasma miRNAs were identified as aberrantly expressed in HBeAg positive and HBeAg negative children (p<0.001). Levels of all of the miRNAs were upregulated in HBeAg positive children compared with in HBeAg negative children. A positive correlation was furthermore found between plasma levels of the identified miRNAs and HBV DNA (p<0.001). Conclusion: We are the first to investigate the plasma miRNA profile of children chronically infected with HBV. Our data indicates the existence of a relationship between abundance of circulating miRNAs and immunological stages in the natural course of disease. Certain miRNAs may contribute to the establishment and maintenance of CHB in children. Further studies are warranted to advance understanding of miRNAs in the pathogenesis of CHB, hopefully leading to the identification of future therapeutic targets.

Originalsprog	Engelsk
Tidsskrift	PLOS ONE
Vol/bind	8
Udgave nummer	3
Sider (fra-til)	e58236
ISSN	1932-6203
DOI	https://doi.org/10.1371/journal.pone.0058236
Status	Udgivet - 4 mar. 2013

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title = "Differential plasma microRNA profiles in HBeAg positive and HBeAg negative children with chronic hepatitis B",

abstract = "Background and Aim: Children chronically infected with hepatitis B virus (HBV) are at high risk of progressive liver disease. However, no treatment is available that is consistently effective in curing chronic hepatitis B (CHB) in children. Improved understanding of the natural course of disease is warranted. Identification of specific microRNA (miRNA) profiles in children chronically infected with HBV may provide insight into the pathogenesis of CHB and lead to advances in the management of children with CHB. Patients and Methods: MiRNA PCR panels were employed to screen plasma levels of 739 miRNAs in pooled samples from HBeAg positive, HBeAg negative, and healthy children. The three groups' plasma miRNA profiles were compared, and aberrantly expressed miRNAs were identified. The identified miRNAs were then validated. Individual RT-qPCRs were performed on plasma from 34 HBeAg positive, 26 HBeAg negative, and 60 healthy children. Results: A panel of 16 plasma miRNAs were identified as aberrantly expressed in HBeAg positive and HBeAg negative children (p<0.001). Levels of all of the miRNAs were upregulated in HBeAg positive children compared with in HBeAg negative children. A positive correlation was furthermore found between plasma levels of the identified miRNAs and HBV DNA (p<0.001). Conclusion: We are the first to investigate the plasma miRNA profile of children chronically infected with HBV. Our data indicates the existence of a relationship between abundance of circulating miRNAs and immunological stages in the natural course of disease. Certain miRNAs may contribute to the establishment and maintenance of CHB in children. Further studies are warranted to advance understanding of miRNAs in the pathogenesis of CHB, hopefully leading to the identification of future therapeutic targets.",

keywords = "Adolescent, Case-Control Studies, Child, Child, Preschool, DNA, Viral/blood, Female, Hepatitis B e Antigens/blood, Hepatitis B virus/immunology, Hepatitis B, Chronic/immunology, Humans, Infant, Liver/immunology, Male, MicroRNAs/blood, Polymerase Chain Reaction",

author = "Winther, {Thilde Nordmann} and Bang-Berthelsen, {Claus Heiner} and Heiberg, {Ida Louise} and Flemming Pociot and Birthe Hogh",

year = "2013",

month = mar,

day = "4",

doi = "10.1371/journal.pone.0058236",

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TY - JOUR

T1 - Differential plasma microRNA profiles in HBeAg positive and HBeAg negative children with chronic hepatitis B

AU - Winther, Thilde Nordmann

AU - Bang-Berthelsen, Claus Heiner

AU - Heiberg, Ida Louise

AU - Pociot, Flemming

AU - Hogh, Birthe

PY - 2013/3/4

Y1 - 2013/3/4

N2 - Background and Aim: Children chronically infected with hepatitis B virus (HBV) are at high risk of progressive liver disease. However, no treatment is available that is consistently effective in curing chronic hepatitis B (CHB) in children. Improved understanding of the natural course of disease is warranted. Identification of specific microRNA (miRNA) profiles in children chronically infected with HBV may provide insight into the pathogenesis of CHB and lead to advances in the management of children with CHB. Patients and Methods: MiRNA PCR panels were employed to screen plasma levels of 739 miRNAs in pooled samples from HBeAg positive, HBeAg negative, and healthy children. The three groups' plasma miRNA profiles were compared, and aberrantly expressed miRNAs were identified. The identified miRNAs were then validated. Individual RT-qPCRs were performed on plasma from 34 HBeAg positive, 26 HBeAg negative, and 60 healthy children. Results: A panel of 16 plasma miRNAs were identified as aberrantly expressed in HBeAg positive and HBeAg negative children (p<0.001). Levels of all of the miRNAs were upregulated in HBeAg positive children compared with in HBeAg negative children. A positive correlation was furthermore found between plasma levels of the identified miRNAs and HBV DNA (p<0.001). Conclusion: We are the first to investigate the plasma miRNA profile of children chronically infected with HBV. Our data indicates the existence of a relationship between abundance of circulating miRNAs and immunological stages in the natural course of disease. Certain miRNAs may contribute to the establishment and maintenance of CHB in children. Further studies are warranted to advance understanding of miRNAs in the pathogenesis of CHB, hopefully leading to the identification of future therapeutic targets.

AB - Background and Aim: Children chronically infected with hepatitis B virus (HBV) are at high risk of progressive liver disease. However, no treatment is available that is consistently effective in curing chronic hepatitis B (CHB) in children. Improved understanding of the natural course of disease is warranted. Identification of specific microRNA (miRNA) profiles in children chronically infected with HBV may provide insight into the pathogenesis of CHB and lead to advances in the management of children with CHB. Patients and Methods: MiRNA PCR panels were employed to screen plasma levels of 739 miRNAs in pooled samples from HBeAg positive, HBeAg negative, and healthy children. The three groups' plasma miRNA profiles were compared, and aberrantly expressed miRNAs were identified. The identified miRNAs were then validated. Individual RT-qPCRs were performed on plasma from 34 HBeAg positive, 26 HBeAg negative, and 60 healthy children. Results: A panel of 16 plasma miRNAs were identified as aberrantly expressed in HBeAg positive and HBeAg negative children (p<0.001). Levels of all of the miRNAs were upregulated in HBeAg positive children compared with in HBeAg negative children. A positive correlation was furthermore found between plasma levels of the identified miRNAs and HBV DNA (p<0.001). Conclusion: We are the first to investigate the plasma miRNA profile of children chronically infected with HBV. Our data indicates the existence of a relationship between abundance of circulating miRNAs and immunological stages in the natural course of disease. Certain miRNAs may contribute to the establishment and maintenance of CHB in children. Further studies are warranted to advance understanding of miRNAs in the pathogenesis of CHB, hopefully leading to the identification of future therapeutic targets.

KW - Adolescent

KW - Case-Control Studies

KW - Child

KW - Child, Preschool

KW - DNA, Viral/blood

KW - Female

KW - Hepatitis B e Antigens/blood

KW - Hepatitis B virus/immunology

KW - Hepatitis B, Chronic/immunology

KW - Humans

KW - Infant

KW - Liver/immunology

KW - Male

KW - MicroRNAs/blood

KW - Polymerase Chain Reaction

U2 - 10.1371/journal.pone.0058236

DO - 10.1371/journal.pone.0058236

M3 - Journal article

C2 - 23469271

SN - 1932-6203

VL - 8

SP - e58236

JO - PLOS ONE

JF - PLOS ONE

IS - 3

ER -

Differential plasma microRNA profiles in HBeAg positive and HBeAg negative children with chronic hepatitis B

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