Immunological alterations in pregnant women with acute hepatitis E

Pal, Rishi; Aggarwal, Rakesh; Naik, S. R.; Das, V.; Das, Siddharth Kumar; Naik, Sita

doi:10.1111/j.1440-1746.2005.03875.x

Cited by 115 publications

(91 citation statements)

References 22 publications

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“…To address the role of the CMI response in HEV infection, a quantitative assay for measuring HEV-specific CMI responses is needed. Prior reports examined T cell proliferation Naik et al, 2002;Pal et al, 2005;Srivastava et al, 2007) or flow cytometry (Srivastava et al, 2007) as a surrogate marker for CMI responses to HEV, however, the sensitivity and specificity of these assays were low. During the last ten years, highly sensitive IFN-γ ELISPOT assays have been used successfully for measuring the CMI responses in different diseases (Dheda et al, 2005;Liu et al, 2006;Sun et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

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Characterization of hepatitis E-specific cell-mediated immune response using IFN-γ ELISPOT assay

Shata

Barrett

Shire

et al. 2007

Journal of Immunological Methods

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In developing countries, hepatitis E (HEV) and hepatitis A (HAV) are the major causes of acute viral hepatitis with similar fecooral modes of transmission. In contrast to the high seroprevalence of hepatitis A infection, a low seroprevalence of HEV among children in endemic areas has been reported. These data suggest the possibility that silent HEV infection is undiagnosed by the current available methods. Many of the serological tests used for HEV diagnosis have poor specificity and are unable to differentiate among different genotypes of HEV. Moreover, the RT-PCR used for HEV isolation is only valid for a brief period during the acute stage of infection. Cell-mediated immune (CMI) responses are highly sensitive, and long lasting after sub-clinical infections as shown in HCV and HIV. Our objective was to develop a quantitative assay for cell-mediated immune (CMI) responses in HEV infection as a surrogate marker for HEV exposure in silent infection. Quantitative assessment of the CMI responses in HEV will also help us to evaluate the role of CMI in HEV morbidity. In this study, an HEV-specific interferon-gamma (IFN-γ) ELISPOT assay was optimized to analyze HEV-specific CMI responses. We used peripheral blood mononuclear cells (PBMC) and sera from experimentally infected chimpanzees and from seroconverted and control human subjects to validate the assay. The HEV-specific IFN-γ ELISPOT responses correlated strongly and significantly with anti-HEV ELISA positive/negative results (rho=0.73, p=0.02). Moreover, fine specificities of HEV-specific T cell responses could be identified using overlapping HEV ORF2 peptides.

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Section: Discussionmentioning

confidence: 99%

“…A recent report has suggested that CMI responses and T h1 /T h2 cytokine profiles in pregnant women are highly involved in HEV morbidity (Pal et al, 2005). To address the role of the CMI response in HEV infection, a quantitative assay for measuring HEV-specific CMI responses is needed.…”

Section: Discussionmentioning

confidence: 99%

Characterization of hepatitis E-specific cell-mediated immune response using IFN-γ ELISPOT assay

Shata

Barrett

Shire

et al. 2007

Journal of Immunological Methods

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“…36 The reason underlying the association of hepatitis E and pregnancy is unknown, though immunological or hormonal factors have been proposed. [39][40][41][42] Hepatitis E during pregnancy is also associated with prematurity and low birth weight. 43 The children born to such mothers frequently suffer from hypoglycemia and jaundice, and have an increased perinatal mortality.…”

Section: Relationship Of Hepatitis E With Host Characteristics Inclumentioning

confidence: 99%

Hepatitis E: Epidemiology and Natural History

Aggarwal

2013

Journal of Clinical and Experimental Hepatology

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“…[16][17][18][19][20][21][22][23][24] However, few studies investigated T-cell immunity in HEV infection. Some groups have analyzed HEV-specific cellular immune responses by screening potential T-cell epitopes in the open reading frame (ORF)2 and 3 regions of HEV describing HEV-specific lymphoproliferative responses in patients with acute hepatitis E. 25,26 In addition, pregnant women with acute HEV infection showed a Th2-biased T-cell response 27 and a stronger reactivity against HEV ORF2 and ORF3 proteins was associated with a milder course of disease in acute and fulminant hepatitis E. 28 However, these studies had limitations, as usually only one functional readout was applied and CD4þ and CD8þ T-cell responses were not distinguished. Moreover, and importantly, no study until now has addressed the role of T-cell responses in resolving and chronic HEV infection.…”

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confidence: 99%

Hepatitis E virus (HEV)-specific T-cell responses are associated with control of HEV infection

et al. 2012

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Hepatitis E virus (HEV) infection is usually self-limited but may lead to acute hepatitis and rarely to fulminant hepatic failure. Persistent HEV infections have recently been described in organ transplant recipients receiving immunosuppressive medications, suggesting that HEV is controlled by adaptive immune responses. However, only few studies have investigated HEV-specific T-cell responses and immune correlates for the failure to clear HEV infection have not been established so far. We investigated T-cell responses against HEV in 38 subjects including anti-HEV-positive (exposed, n 5 9) and anti-HEV-negative (n 5 10) healthy controls, 12 anti-HEV-positive but HEV RNA-negative organ transplant recipients, and seven transplant recipients with chronic hepatitis E. Proliferation as well as cytokine production of CD41 and CD81 T cells was studied after stimulation with overlapping peptides spanning all proteins encoded by HEV-open reading frame (ORF)2 and HEV-ORF3. We show that (1) strong and multispecific HEV-specific T-cell responses are present in exposed healthy controls, and to a lesser extent also in recovered patients after transplantation; (2) that these responses are absent in patients with chronic hepatitis E but become detectable after viral clearance; and (3) that HEV-specific T-cell responses can be restored in vitro by blocking the PD-1 or CTLA-4 pathways. However, a combination of PD-1 and CTLA-4 blockade had no synergistic effects. We conclude that chronic hepatitis E is associated with impaired HEV-specific T-cell responses and suggest that enhancing adaptive cellular immunity against HEV might prevent persistent HEV infections. (HEPATOLOGY 2012;55:695-708)

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Immunological alterations in pregnant women with acute hepatitis E

Abstract: These results show the existence of a Th2 bias in pregnant women with acute hepatitis E. The role of this Th2 bias in the greater severity of hepatitis E among pregnant women needs further investigation.

Cited by 115 publications

References 22 publications

Characterization of hepatitis E-specific cell-mediated immune response using IFN-γ ELISPOT assay

Characterization of hepatitis E-specific cell-mediated immune response using IFN-γ ELISPOT assay

Hepatitis E: Epidemiology and Natural History

Hepatitis E virus (HEV)-specific T-cell responses are associated with control of HEV infection

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