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miRNA signatures can predict acute liver failure in hepatitis E infected pregnant females

View Article: PubMed Central - PubMed

ABSTRACT

Background: Acute viral hepatitis E (AVH-E) can often result in acute liver failure (ALF) during pregnancy. microRNAs serve as mediators in drug induced liver failure. We investigated their role as a biomarker in predicting ALF due to HEV (ALF-E).

Methods: We performed next generation sequencing and subsequent validation studies in PBMCs of pregnant (P) self limiting AVH-E, ALF due to HEV (ALF-E) and compared with AVH-E in non-pregnant (NP) females and healthy controls.

Findings: Eleven microRNAs were significantly expressed in response to HEV infection; importantly, miR- 431, 654, 1468 and 4435, were distinctly expressed in pregnant self-limiting AVH-E and healthy females (p = 0.0005), but not in ALF-E. Sixteen exclusive microRNAs differentiated ALF-E from self limiting AVH-E in pregnant females. miR-450b which affects cellular proliferation and metabolic processes through RNF20 and SECB was predominanlty upregulated and correlated with poor outcome (ROC 0.958, p = 0.001).

Interpretation: Our results reveal that a specific microRNA profile can predict fatality in ALF-E in pregnancy. These microRNAs could be exploited as prognostic biomarkers and help in the development of new therapeutic interventions.

No MeSH data available.


Related in: MedlinePlus

(A) Global analysis of small RNAs identified using deep sequencing. (B-C) Frequency of Immune cells in peripheral blood of pregnant and non-pregnant healthy controls(HC) and acute HEV patients. (D) Averaged expression signature of miRs in pooled PBMCs isolated from pregnant AVH-E, ALF-E and HC and non pregnant AVH-E. Pregnant AVH-E and non pregnant AVH-E was compared and also pregnant ALF-E and AVH-E was compared with HC. Each lane represents the average signal log intensity of five patients in each group as independent technical replicates. Expression was displayed in red and green for increased and decreased expression levels and black for no changed expression levels. Color intensity was calibrated to expression level as illustrated at the side of heat map. (E) miR expression data from different groups were applied to principal component analysis. The use of this technical analysis allowed us to visualise the observed variance between groups. (F) Averaged gene expression signature showing decreased global gene expression in AVH-E(P) compared to AVH-E(NP). (G) Heat maps of gene expression in pregnant ALF-E, AVH-E and HC. (H) Principal component analysis (PCA) visualise observed variance in groups.
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fig0005: (A) Global analysis of small RNAs identified using deep sequencing. (B-C) Frequency of Immune cells in peripheral blood of pregnant and non-pregnant healthy controls(HC) and acute HEV patients. (D) Averaged expression signature of miRs in pooled PBMCs isolated from pregnant AVH-E, ALF-E and HC and non pregnant AVH-E. Pregnant AVH-E and non pregnant AVH-E was compared and also pregnant ALF-E and AVH-E was compared with HC. Each lane represents the average signal log intensity of five patients in each group as independent technical replicates. Expression was displayed in red and green for increased and decreased expression levels and black for no changed expression levels. Color intensity was calibrated to expression level as illustrated at the side of heat map. (E) miR expression data from different groups were applied to principal component analysis. The use of this technical analysis allowed us to visualise the observed variance between groups. (F) Averaged gene expression signature showing decreased global gene expression in AVH-E(P) compared to AVH-E(NP). (G) Heat maps of gene expression in pregnant ALF-E, AVH-E and HC. (H) Principal component analysis (PCA) visualise observed variance in groups.

Mentions: Small RNAs play a major role in post-transcriptional regulation of gene expression and particularly regulate anti-viral defence mechanisms. First, we assessed the total number of differentially expressed small RNAs in ALF-E(P), AVH-E(P), HC(P) and AVH-E(NP) from total PBMCs using Illumina GAIIx genome analyzer deep sequencing platform. For each group, deep sequencing generated an average of 30 million reads of 50 bp length. Expression of total small RNAs was masked in pregnant females than non pregnant, although, expression of miRs waspredominant in all groups (Fig. 1A). Low expression of miRs may be related with overall decline in immune cells during pregnancy (Fig. 1B).


miRNA signatures can predict acute liver failure in hepatitis E infected pregnant females
(A) Global analysis of small RNAs identified using deep sequencing. (B-C) Frequency of Immune cells in peripheral blood of pregnant and non-pregnant healthy controls(HC) and acute HEV patients. (D) Averaged expression signature of miRs in pooled PBMCs isolated from pregnant AVH-E, ALF-E and HC and non pregnant AVH-E. Pregnant AVH-E and non pregnant AVH-E was compared and also pregnant ALF-E and AVH-E was compared with HC. Each lane represents the average signal log intensity of five patients in each group as independent technical replicates. Expression was displayed in red and green for increased and decreased expression levels and black for no changed expression levels. Color intensity was calibrated to expression level as illustrated at the side of heat map. (E) miR expression data from different groups were applied to principal component analysis. The use of this technical analysis allowed us to visualise the observed variance between groups. (F) Averaged gene expression signature showing decreased global gene expression in AVH-E(P) compared to AVH-E(NP). (G) Heat maps of gene expression in pregnant ALF-E, AVH-E and HC. (H) Principal component analysis (PCA) visualise observed variance in groups.
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Related In: Results  -  Collection

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fig0005: (A) Global analysis of small RNAs identified using deep sequencing. (B-C) Frequency of Immune cells in peripheral blood of pregnant and non-pregnant healthy controls(HC) and acute HEV patients. (D) Averaged expression signature of miRs in pooled PBMCs isolated from pregnant AVH-E, ALF-E and HC and non pregnant AVH-E. Pregnant AVH-E and non pregnant AVH-E was compared and also pregnant ALF-E and AVH-E was compared with HC. Each lane represents the average signal log intensity of five patients in each group as independent technical replicates. Expression was displayed in red and green for increased and decreased expression levels and black for no changed expression levels. Color intensity was calibrated to expression level as illustrated at the side of heat map. (E) miR expression data from different groups were applied to principal component analysis. The use of this technical analysis allowed us to visualise the observed variance between groups. (F) Averaged gene expression signature showing decreased global gene expression in AVH-E(P) compared to AVH-E(NP). (G) Heat maps of gene expression in pregnant ALF-E, AVH-E and HC. (H) Principal component analysis (PCA) visualise observed variance in groups.
Mentions: Small RNAs play a major role in post-transcriptional regulation of gene expression and particularly regulate anti-viral defence mechanisms. First, we assessed the total number of differentially expressed small RNAs in ALF-E(P), AVH-E(P), HC(P) and AVH-E(NP) from total PBMCs using Illumina GAIIx genome analyzer deep sequencing platform. For each group, deep sequencing generated an average of 30 million reads of 50 bp length. Expression of total small RNAs was masked in pregnant females than non pregnant, although, expression of miRs waspredominant in all groups (Fig. 1A). Low expression of miRs may be related with overall decline in immune cells during pregnancy (Fig. 1B).

View Article: PubMed Central - PubMed

ABSTRACT

Background: Acute viral hepatitis E (AVH-E) can often result in acute liver failure (ALF) during pregnancy. microRNAs serve as mediators in drug induced liver failure. We investigated their role as a biomarker in predicting ALF due to HEV (ALF-E).

Methods: We performed next generation sequencing and subsequent validation studies in PBMCs of pregnant (P) self limiting AVH-E, ALF due to HEV (ALF-E) and compared with AVH-E in non-pregnant (NP) females and healthy controls.

Findings: Eleven microRNAs were significantly expressed in response to HEV infection; importantly, miR- 431, 654, 1468 and 4435, were distinctly expressed in pregnant self-limiting AVH-E and healthy females (p = 0.0005), but not in ALF-E. Sixteen exclusive microRNAs differentiated ALF-E from self limiting AVH-E in pregnant females. miR-450b which affects cellular proliferation and metabolic processes through RNF20 and SECB was predominanlty upregulated and correlated with poor outcome (ROC 0.958, p = 0.001).

Interpretation: Our results reveal that a specific microRNA profile can predict fatality in ALF-E in pregnancy. These microRNAs could be exploited as prognostic biomarkers and help in the development of new therapeutic interventions.

No MeSH data available.


Related in: MedlinePlus