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.
abstract: 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.
authors.affiliation: Hepatitis Division, National Institute of Virology, Pashan, Pune, Maharashtra, India.
authors.forename: Ashwini Y
authors.initials: AY
authors.lastname: Ramdasi
authors.affiliation: Hepatitis Division, National Institute of Virology, Pashan, Pune, Maharashtra, India.
authors.forename: Ravi P
authors.initials: RP
authors.lastname: Arya
authors.affiliation: Hepatitis Division, National Institute of Virology, Pashan, Pune, Maharashtra, India.
authors.forename: Vidya A
authors.initials: VA
authors.lastname: Arankalle
mesh_terms: D000328:Adult; D001774:Blood Chemical Analysis; D016022:Case-Control Studies; D016000:Cluster Analysis; D016207:Cytokines / Q000097:blood* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006508:Hepatitis Antibodies / Q000097:blood / Q000276:immunology*; D016751:Hepatitis E / Q000097:blood* / Q000209:etiology* / Q000235:genetics; D016752:Hepatitis E virus / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D055815:Young Adult
chemical_list: D016207:Cytokines; D006508:Hepatitis Antibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M
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