Effect of pregnancy on anti-HEV antibody titres, plasma cytokines and the corresponding gene expression levels in the PBMCs of patients presenting with self-recovering clinical and subclinical hepatitis E

High mortality in pregnant women (PR) is a characteristic of hepatitis E in developing countries. To understand the pathogenesis of HEV infection in self-limiting disease during pregnancy, we compared clinical (PR-patients) and subclinical-HEV-infections in pregnant women in the first (SC-PR-1) and...

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Veröffentlicht in:PloS one 2014-08, Vol.9 (8), p.e103257-e103257
Hauptverfasser: Ramdasi, Ashwini Y, Arya, Ravi P, Arankalle, Vidya A
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Arya, Ravi P
Arankalle, Vidya A
description High mortality in pregnant women (PR) is a characteristic of hepatitis E in developing countries. To understand the pathogenesis of HEV infection in self-limiting disease during pregnancy, we compared clinical (PR-patients) and subclinical-HEV-infections in pregnant women in the first (SC-PR-1) and later (2nd and 3rd, SC-PR-2+3) trimesters with the respective healthy controls and acute non-PR patients. The SC-PR-2+3 exhibited lower ALT, bilirubin levels, anti-HEV-IgM/IgG titres than the acute-PR/non-PR-patients (p
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To understand the pathogenesis of HEV infection in self-limiting disease during pregnancy, we compared clinical (PR-patients) and subclinical-HEV-infections in pregnant women in the first (SC-PR-1) and later (2nd and 3rd, SC-PR-2+3) trimesters with the respective healthy controls and acute non-PR patients. The SC-PR-2+3 exhibited lower ALT, bilirubin levels, anti-HEV-IgM/IgG titres than the acute-PR/non-PR-patients (p<0.05-0.0001). IFNγ/IL4ratios indicated Th2/Th1 bias in non-PR and PR-patients respectively. Raised levels of 10/20 plasma cytokines in the non-PR-patients reflect predominant inflammatory response, unaltered- IFNγ/reduced-IFNα responses and a robust chemokine secretion. On contrary, the acute-PR-patients exhibited drastic reduction in majority of the cytokines relative to in the non-PR-patients. Importantly, diminished or unaltered response was noted in the acute-PR-group when compared to the corresponding controls. The only exception was sIL2RA, increasing in both patient categories. Of the 14 genes evaluated, the expression of IFNγ/IL10/IL1A/IL7/CCL2/CCL3/CXCL8/CXCL10 was higher in the non-PR patients. Of these, the expression of IFNγ/IL10/IL1A/CCL2/CCL3/CXCL8 and, additionally, IL2/IL6/TNF genes was higher in the clinical-PRs. Almost identical pattern was noted in the control-PR-2+3 category indicating no influence of HEV infection. Comparison of patient-categories identified significant elevation of IFNγ(P<0.001), CCL2(p<0.01), CXCL8(P<0.05), IL1B(p<0.05) and IL10(P<0.0001) and decrease in CXCL10(<0.05) in the PR-patients. The results suggest antibody-dependent disease severity and impaired immune response in the PR patients. Higher expression of cytokine-genes in the PBMCs did not correlate with the plasma-cytokine levels in the PR-patients.]]></description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0103257</identifier><identifier>PMID: 25084004</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Antibodies ; Bilirubin ; Biology and Life Sciences ; Blood Chemical Analysis ; Case-Control Studies ; CCL3 protein ; Cluster Analysis ; Comparative analysis ; CXCL10 protein ; Cytokines ; Cytokines - blood ; Cytokines - genetics ; Developing countries ; Development and progression ; Disease ; Disease control ; Epidemics ; Female ; Gene Expression ; Gene Expression Profiling ; Genes ; Health aspects ; Hepatitis ; Hepatitis Antibodies - blood ; Hepatitis Antibodies - immunology ; Hepatitis E ; Hepatitis E - blood ; Hepatitis E - etiology ; Hepatitis E - genetics ; Hepatitis E virus - immunology ; Host-Pathogen Interactions - genetics ; Host-Pathogen Interactions - immunology ; Humans ; Immune response ; Immune system ; Immunoglobulin G ; Immunoglobulin G - blood ; Immunoglobulin G - immunology ; Immunoglobulin M ; Immunoglobulin M - blood ; Immunoglobulin M - immunology ; Immunoglobulins ; Infection ; Infections ; Inflammation ; Inflammatory response ; Influenza ; Interferon ; Interleukin 1 ; Interleukin 10 ; Interleukin 2 ; Interleukin 6 ; Interleukin 7 ; LDCs ; Leukocytes, Mononuclear - metabolism ; Liver Function Tests ; Lymphocytes T ; Male ; Medicine and Health Sciences ; Monocyte chemoattractant protein 1 ; Mortality ; Pathogenesis ; Patients ; Plasma ; Pregnancy ; Pregnancy Complications, Infectious ; Pregnant women ; Tumor necrosis factor ; Viral infections ; Virology ; Womens health ; Young Adult ; γ-Interferon</subject><ispartof>PloS one, 2014-08, Vol.9 (8), p.e103257-e103257</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Ramdasi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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To understand the pathogenesis of HEV infection in self-limiting disease during pregnancy, we compared clinical (PR-patients) and subclinical-HEV-infections in pregnant women in the first (SC-PR-1) and later (2nd and 3rd, SC-PR-2+3) trimesters with the respective healthy controls and acute non-PR patients. The SC-PR-2+3 exhibited lower ALT, bilirubin levels, anti-HEV-IgM/IgG titres than the acute-PR/non-PR-patients (p<0.05-0.0001). IFNγ/IL4ratios indicated Th2/Th1 bias in non-PR and PR-patients respectively. Raised levels of 10/20 plasma cytokines in the non-PR-patients reflect predominant inflammatory response, unaltered- IFNγ/reduced-IFNα responses and a robust chemokine secretion. On contrary, the acute-PR-patients exhibited drastic reduction in majority of the cytokines relative to in the non-PR-patients. Importantly, diminished or unaltered response was noted in the acute-PR-group when compared to the corresponding controls. The only exception was sIL2RA, increasing in both patient categories. Of the 14 genes evaluated, the expression of IFNγ/IL10/IL1A/IL7/CCL2/CCL3/CXCL8/CXCL10 was higher in the non-PR patients. Of these, the expression of IFNγ/IL10/IL1A/CCL2/CCL3/CXCL8 and, additionally, IL2/IL6/TNF genes was higher in the clinical-PRs. Almost identical pattern was noted in the control-PR-2+3 category indicating no influence of HEV infection. Comparison of patient-categories identified significant elevation of IFNγ(P<0.001), CCL2(p<0.01), CXCL8(P<0.05), IL1B(p<0.05) and IL10(P<0.0001) and decrease in CXCL10(<0.05) in the PR-patients. The results suggest antibody-dependent disease severity and impaired immune response in the PR patients. Higher expression of cytokine-genes in the PBMCs did not correlate with the plasma-cytokine levels in the PR-patients.]]></description><subject>Adult</subject><subject>Antibodies</subject><subject>Bilirubin</subject><subject>Biology and Life Sciences</subject><subject>Blood Chemical Analysis</subject><subject>Case-Control Studies</subject><subject>CCL3 protein</subject><subject>Cluster Analysis</subject><subject>Comparative analysis</subject><subject>CXCL10 protein</subject><subject>Cytokines</subject><subject>Cytokines - blood</subject><subject>Cytokines - genetics</subject><subject>Developing countries</subject><subject>Development and progression</subject><subject>Disease</subject><subject>Disease control</subject><subject>Epidemics</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Gene Expression Profiling</subject><subject>Genes</subject><subject>Health aspects</subject><subject>Hepatitis</subject><subject>Hepatitis Antibodies - blood</subject><subject>Hepatitis Antibodies - immunology</subject><subject>Hepatitis E</subject><subject>Hepatitis E - blood</subject><subject>Hepatitis E - etiology</subject><subject>Hepatitis E - genetics</subject><subject>Hepatitis E virus - immunology</subject><subject>Host-Pathogen Interactions - genetics</subject><subject>Host-Pathogen Interactions - immunology</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulin G - blood</subject><subject>Immunoglobulin G - immunology</subject><subject>Immunoglobulin M</subject><subject>Immunoglobulin M - blood</subject><subject>Immunoglobulin M - immunology</subject><subject>Immunoglobulins</subject><subject>Infection</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Inflammatory response</subject><subject>Influenza</subject><subject>Interferon</subject><subject>Interleukin 1</subject><subject>Interleukin 10</subject><subject>Interleukin 2</subject><subject>Interleukin 6</subject><subject>Interleukin 7</subject><subject>LDCs</subject><subject>Leukocytes, Mononuclear - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ramdasi, Ashwini Y</au><au>Arya, Ravi P</au><au>Arankalle, Vidya A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of pregnancy on anti-HEV antibody titres, plasma cytokines and the corresponding gene expression levels in the PBMCs of patients presenting with self-recovering clinical and subclinical hepatitis E</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-08-01</date><risdate>2014</risdate><volume>9</volume><issue>8</issue><spage>e103257</spage><epage>e103257</epage><pages>e103257-e103257</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract><![CDATA[High mortality in pregnant women (PR) is a characteristic of hepatitis E in developing countries. To understand the pathogenesis of HEV infection in self-limiting disease during pregnancy, we compared clinical (PR-patients) and subclinical-HEV-infections in pregnant women in the first (SC-PR-1) and later (2nd and 3rd, SC-PR-2+3) trimesters with the respective healthy controls and acute non-PR patients. The SC-PR-2+3 exhibited lower ALT, bilirubin levels, anti-HEV-IgM/IgG titres than the acute-PR/non-PR-patients (p<0.05-0.0001). IFNγ/IL4ratios indicated Th2/Th1 bias in non-PR and PR-patients respectively. Raised levels of 10/20 plasma cytokines in the non-PR-patients reflect predominant inflammatory response, unaltered- IFNγ/reduced-IFNα responses and a robust chemokine secretion. On contrary, the acute-PR-patients exhibited drastic reduction in majority of the cytokines relative to in the non-PR-patients. Importantly, diminished or unaltered response was noted in the acute-PR-group when compared to the corresponding controls. The only exception was sIL2RA, increasing in both patient categories. Of the 14 genes evaluated, the expression of IFNγ/IL10/IL1A/IL7/CCL2/CCL3/CXCL8/CXCL10 was higher in the non-PR patients. Of these, the expression of IFNγ/IL10/IL1A/CCL2/CCL3/CXCL8 and, additionally, IL2/IL6/TNF genes was higher in the clinical-PRs. Almost identical pattern was noted in the control-PR-2+3 category indicating no influence of HEV infection. Comparison of patient-categories identified significant elevation of IFNγ(P<0.001), CCL2(p<0.01), CXCL8(P<0.05), IL1B(p<0.05) and IL10(P<0.0001) and decrease in CXCL10(<0.05) in the PR-patients. The results suggest antibody-dependent disease severity and impaired immune response in the PR patients. Higher expression of cytokine-genes in the PBMCs did not correlate with the plasma-cytokine levels in the PR-patients.]]></abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25084004</pmid><doi>10.1371/journal.pone.0103257</doi><oa>free_for_read</oa></addata></record>
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1932-6203
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subjects Adult
Antibodies
Bilirubin
Biology and Life Sciences
Blood Chemical Analysis
Case-Control Studies
CCL3 protein
Cluster Analysis
Comparative analysis
CXCL10 protein
Cytokines
Cytokines - blood
Cytokines - genetics
Developing countries
Development and progression
Disease
Disease control
Epidemics
Female
Gene Expression
Gene Expression Profiling
Genes
Health aspects
Hepatitis
Hepatitis Antibodies - blood
Hepatitis Antibodies - immunology
Hepatitis E
Hepatitis E - blood
Hepatitis E - etiology
Hepatitis E - genetics
Hepatitis E virus - immunology
Host-Pathogen Interactions - genetics
Host-Pathogen Interactions - immunology
Humans
Immune response
Immune system
Immunoglobulin G
Immunoglobulin G - blood
Immunoglobulin G - immunology
Immunoglobulin M
Immunoglobulin M - blood
Immunoglobulin M - immunology
Immunoglobulins
Infection
Infections
Inflammation
Inflammatory response
Influenza
Interferon
Interleukin 1
Interleukin 10
Interleukin 2
Interleukin 6
Interleukin 7
LDCs
Leukocytes, Mononuclear - metabolism
Liver Function Tests
Lymphocytes T
Male
Medicine and Health Sciences
Monocyte chemoattractant protein 1
Mortality
Pathogenesis
Patients
Plasma
Pregnancy
Pregnancy Complications, Infectious
Pregnant women
Tumor necrosis factor
Viral infections
Virology
Womens health
Young Adult
γ-Interferon
title Effect of pregnancy on anti-HEV antibody titres, plasma cytokines and the corresponding gene expression levels in the PBMCs of patients presenting with self-recovering clinical and subclinical hepatitis E
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