Bayesian analysis of cytokines and chemokine identifies immune pathways of HBsAg loss during chronic hepatitis B treatment

Abstract Our objective was to examine differences in cytokine/chemokine response in chronic hepatitis B(CHB) patients to understand the immune mechanism of HBsAg loss (functional cure) during antiviral therapy. We used an unbiased machine learning strategy to unravel the immune pathways in CHB nucle...

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Autores principales:	Sriram Narayanan, Veonice Bijin Au, Atefeh Khakpoor, Cheng Yan, Patricia J. Ahl, Nivashini Kaliaperumal, Bernett Lee, Wen Wei Xiang, Juling Wang, Chris Lee, Amy Tay, Seng Gee Lim, John E. Connolly
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dd17137d36974df3b1796e6222c13612
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spelling	oai:doaj.org-article:dd17137d36974df3b1796e6222c136122021-12-02T18:18:06ZBayesian analysis of cytokines and chemokine identifies immune pathways of HBsAg loss during chronic hepatitis B treatment10.1038/s41598-021-86836-52045-2322https://doaj.org/article/dd17137d36974df3b1796e6222c136122021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86836-5https://doaj.org/toc/2045-2322Abstract Our objective was to examine differences in cytokine/chemokine response in chronic hepatitis B(CHB) patients to understand the immune mechanism of HBsAg loss (functional cure) during antiviral therapy. We used an unbiased machine learning strategy to unravel the immune pathways in CHB nucleo(t)side analogue-treated patients who achieved HBsAg loss with peg-interferon-α(peg-IFN-α) add-on or switch treatment in a randomised clinical trial. Cytokines/chemokines from plasma were compared between those with/without HBsAg loss, at baseline, before and after HBsAg loss. Peg-IFN-α treatment resulted in higher levels of IL-27, IL-12p70, IL-18, IL-13, IL-4, IL-22 and GM-CSF prior to HBsAg loss. Probabilistic network analysis of cytokines, chemokines and soluble factors suggested a dynamic dendritic cell driven NK and T cell immune response associated with HBsAg loss. Bayesian network analysis showed a dominant myeloid-driven type 1 inflammatory response with a MIG and I-TAC central module contributing to HBsAg loss in the add-on arm. In the switch arm, HBsAg loss was associated with a T cell activation module exemplified by high levels of CD40L suggesting T cell activation. Our findings show that more than one immune pathway to HBsAg loss was found with peg-IFN-α therapy; by myeloid-driven Type 1 response in one instance, and T cell activation in the other.Sriram NarayananVeonice Bijin AuAtefeh KhakpoorCheng YanPatricia J. AhlNivashini KaliaperumalBernett LeeWen Wei XiangJuling WangChris LeeAmy TaySeng Gee LimJohn E. ConnollyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sriram Narayanan Veonice Bijin Au Atefeh Khakpoor Cheng Yan Patricia J. Ahl Nivashini Kaliaperumal Bernett Lee Wen Wei Xiang Juling Wang Chris Lee Amy Tay Seng Gee Lim John E. Connolly Bayesian analysis of cytokines and chemokine identifies immune pathways of HBsAg loss during chronic hepatitis B treatment
description	Abstract Our objective was to examine differences in cytokine/chemokine response in chronic hepatitis B(CHB) patients to understand the immune mechanism of HBsAg loss (functional cure) during antiviral therapy. We used an unbiased machine learning strategy to unravel the immune pathways in CHB nucleo(t)side analogue-treated patients who achieved HBsAg loss with peg-interferon-α(peg-IFN-α) add-on or switch treatment in a randomised clinical trial. Cytokines/chemokines from plasma were compared between those with/without HBsAg loss, at baseline, before and after HBsAg loss. Peg-IFN-α treatment resulted in higher levels of IL-27, IL-12p70, IL-18, IL-13, IL-4, IL-22 and GM-CSF prior to HBsAg loss. Probabilistic network analysis of cytokines, chemokines and soluble factors suggested a dynamic dendritic cell driven NK and T cell immune response associated with HBsAg loss. Bayesian network analysis showed a dominant myeloid-driven type 1 inflammatory response with a MIG and I-TAC central module contributing to HBsAg loss in the add-on arm. In the switch arm, HBsAg loss was associated with a T cell activation module exemplified by high levels of CD40L suggesting T cell activation. Our findings show that more than one immune pathway to HBsAg loss was found with peg-IFN-α therapy; by myeloid-driven Type 1 response in one instance, and T cell activation in the other.
format	article
author	Sriram Narayanan Veonice Bijin Au Atefeh Khakpoor Cheng Yan Patricia J. Ahl Nivashini Kaliaperumal Bernett Lee Wen Wei Xiang Juling Wang Chris Lee Amy Tay Seng Gee Lim John E. Connolly
author_facet	Sriram Narayanan Veonice Bijin Au Atefeh Khakpoor Cheng Yan Patricia J. Ahl Nivashini Kaliaperumal Bernett Lee Wen Wei Xiang Juling Wang Chris Lee Amy Tay Seng Gee Lim John E. Connolly
author_sort	Sriram Narayanan
title	Bayesian analysis of cytokines and chemokine identifies immune pathways of HBsAg loss during chronic hepatitis B treatment
title_short	Bayesian analysis of cytokines and chemokine identifies immune pathways of HBsAg loss during chronic hepatitis B treatment
title_full	Bayesian analysis of cytokines and chemokine identifies immune pathways of HBsAg loss during chronic hepatitis B treatment
title_fullStr	Bayesian analysis of cytokines and chemokine identifies immune pathways of HBsAg loss during chronic hepatitis B treatment
title_full_unstemmed	Bayesian analysis of cytokines and chemokine identifies immune pathways of HBsAg loss during chronic hepatitis B treatment
title_sort	bayesian analysis of cytokines and chemokine identifies immune pathways of hbsag loss during chronic hepatitis b treatment
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/dd17137d36974df3b1796e6222c13612
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Bayesian analysis of cytokines and chemokine identifies immune pathways of HBsAg loss during chronic hepatitis B treatment

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