Overt Acute Hepatitis B Deteriorates in Females: Destructive Immunity With an Exaggerated Interleukin-17 Pathway

Background and AimsWe previously showed that overt acute hepatitis B (AHB) was more severe in female patients. Using the same cohort and AHB mouse model, we examined the underlying mechanism.MethodsBaseline biochemistry, virological and cytokine assays, and T helper (Th)1 and Th2 immune markers of 1...

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Autores principales:	Ming-Ling Chang, Chau-Ting Yeh, Rong-Nan Chien, Yun-Fan Liaw
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	female AHB IFN-γ IL-4 IL-17 Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/6f22ec04746344c48589211ca6a5375d
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spelling	oai:doaj.org-article:6f22ec04746344c48589211ca6a5375d2021-11-11T05:05:58ZOvert Acute Hepatitis B Deteriorates in Females: Destructive Immunity With an Exaggerated Interleukin-17 Pathway1664-322410.3389/fimmu.2021.631976https://doaj.org/article/6f22ec04746344c48589211ca6a5375d2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.631976/fullhttps://doaj.org/toc/1664-3224Background and AimsWe previously showed that overt acute hepatitis B (AHB) was more severe in female patients. Using the same cohort and AHB mouse model, we examined the underlying mechanism.MethodsBaseline biochemistry, virological and cytokine assays, and T helper (Th)1 and Th2 immune markers of 118 consecutive patients were analyzed. The decompensated livers of AHB and chronic hepatitis B (CHB) patients who underwent liver transplantation were analyzed immunohistochemically. B6 mice were hydrodynamically injected with pHBV1.3 plasmids.ResultsDecompensated AHB patients (n=41) were older, more often female, and had higher alanine aminotransferase (ALT), soluble programmed cell death protein 1 (sPD-1) levels, and neutrophil-lymphocyte ratios but lower rates of HBeAg positivity and quantitative HBsAg, interferon (IFN)-γ-inducible protein 10 (IP-10), IFN-γ, and interleukin-4 (IL-4) levels than the compensated patients. Female sex (95% CI OR=1.07~54.9), age (1.06~1.40), and ALT levels (1.001~1.004) were associated with hepatic decompensation. Higher sPD-1 but lower IFN-γ and IL-4 levels were observed in female patients. Compared to CHB, decompensated AHB livers had more IL-17-positive cells but fewer HBsAg-positive cells and lower CD4/CD8 ratios. Higher serum IL-17 levels were noted in the female AHB mice than those in the males.ConclusionsFemales predominated in decompensated AHB, in which downregulated IFN-γ and IL-4 with augmented hepatic IL-17-positive cell development indicated accelerating destructive immunity to enhance viral clearance. The early surge of serum IL-17 was confirmed in the female AHB mice. Targeting the pathway involving IFN-γ, IL-4, and IL-17 might prevent liver transplantation or fatality in decompensated AHB.Ming-Ling ChangMing-Ling ChangChau-Ting YehChau-Ting YehRong-Nan ChienRong-Nan ChienYun-Fan LiawYun-Fan LiawFrontiers Media S.A.articlefemaleAHBIFN-γIL-4IL-17Immunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	female AHB IFN-γ IL-4 IL-17 Immunologic diseases. Allergy RC581-607
spellingShingle	female AHB IFN-γ IL-4 IL-17 Immunologic diseases. Allergy RC581-607 Ming-Ling Chang Ming-Ling Chang Chau-Ting Yeh Chau-Ting Yeh Rong-Nan Chien Rong-Nan Chien Yun-Fan Liaw Yun-Fan Liaw Overt Acute Hepatitis B Deteriorates in Females: Destructive Immunity With an Exaggerated Interleukin-17 Pathway
description	Background and AimsWe previously showed that overt acute hepatitis B (AHB) was more severe in female patients. Using the same cohort and AHB mouse model, we examined the underlying mechanism.MethodsBaseline biochemistry, virological and cytokine assays, and T helper (Th)1 and Th2 immune markers of 118 consecutive patients were analyzed. The decompensated livers of AHB and chronic hepatitis B (CHB) patients who underwent liver transplantation were analyzed immunohistochemically. B6 mice were hydrodynamically injected with pHBV1.3 plasmids.ResultsDecompensated AHB patients (n=41) were older, more often female, and had higher alanine aminotransferase (ALT), soluble programmed cell death protein 1 (sPD-1) levels, and neutrophil-lymphocyte ratios but lower rates of HBeAg positivity and quantitative HBsAg, interferon (IFN)-γ-inducible protein 10 (IP-10), IFN-γ, and interleukin-4 (IL-4) levels than the compensated patients. Female sex (95% CI OR=1.07~54.9), age (1.06~1.40), and ALT levels (1.001~1.004) were associated with hepatic decompensation. Higher sPD-1 but lower IFN-γ and IL-4 levels were observed in female patients. Compared to CHB, decompensated AHB livers had more IL-17-positive cells but fewer HBsAg-positive cells and lower CD4/CD8 ratios. Higher serum IL-17 levels were noted in the female AHB mice than those in the males.ConclusionsFemales predominated in decompensated AHB, in which downregulated IFN-γ and IL-4 with augmented hepatic IL-17-positive cell development indicated accelerating destructive immunity to enhance viral clearance. The early surge of serum IL-17 was confirmed in the female AHB mice. Targeting the pathway involving IFN-γ, IL-4, and IL-17 might prevent liver transplantation or fatality in decompensated AHB.
format	article
author	Ming-Ling Chang Ming-Ling Chang Chau-Ting Yeh Chau-Ting Yeh Rong-Nan Chien Rong-Nan Chien Yun-Fan Liaw Yun-Fan Liaw
author_facet	Ming-Ling Chang Ming-Ling Chang Chau-Ting Yeh Chau-Ting Yeh Rong-Nan Chien Rong-Nan Chien Yun-Fan Liaw Yun-Fan Liaw
author_sort	Ming-Ling Chang
title	Overt Acute Hepatitis B Deteriorates in Females: Destructive Immunity With an Exaggerated Interleukin-17 Pathway
title_short	Overt Acute Hepatitis B Deteriorates in Females: Destructive Immunity With an Exaggerated Interleukin-17 Pathway
title_full	Overt Acute Hepatitis B Deteriorates in Females: Destructive Immunity With an Exaggerated Interleukin-17 Pathway
title_fullStr	Overt Acute Hepatitis B Deteriorates in Females: Destructive Immunity With an Exaggerated Interleukin-17 Pathway
title_full_unstemmed	Overt Acute Hepatitis B Deteriorates in Females: Destructive Immunity With an Exaggerated Interleukin-17 Pathway
title_sort	overt acute hepatitis b deteriorates in females: destructive immunity with an exaggerated interleukin-17 pathway
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6f22ec04746344c48589211ca6a5375d
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Overt Acute Hepatitis B Deteriorates in Females: Destructive Immunity With an Exaggerated Interleukin-17 Pathway

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