CitH3: a reliable blood biomarker for diagnosis and treatment of endotoxic shock

Abstract Current biomarkers for sepsis are limited by their non-specificity, short half-life, and insensitive response to therapy. Recently, we have demonstrated that citrullinated histone H3(CitH3) is released into the blood from neutrophil extracellular traps(NETs) in response to severe infection,...

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Autores principales:	Baihong Pan, Hasan B. Alam, Wei Chong, James Mobley, Baoling Liu, Qiufang Deng, Yinjian Liang, Yanming Wang, Eric Chen, Tianbing Wang, Muneesh Tewari, Yongqing Li
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0aab2b3818fa475fbc953f16e0260f02
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spelling	oai:doaj.org-article:0aab2b3818fa475fbc953f16e0260f022021-12-02T11:41:00ZCitH3: a reliable blood biomarker for diagnosis and treatment of endotoxic shock10.1038/s41598-017-09337-42045-2322https://doaj.org/article/0aab2b3818fa475fbc953f16e0260f022017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09337-4https://doaj.org/toc/2045-2322Abstract Current biomarkers for sepsis are limited by their non-specificity, short half-life, and insensitive response to therapy. Recently, we have demonstrated that citrullinated histone H3(CitH3) is released into the blood from neutrophil extracellular traps(NETs) in response to severe infection, and CitH3 may be a potential biomarker for sepsis. In the present study, we found that NET components were released in mouse models of both lipopolysaccharide(LPS)-induced shock (LPSS) and hemorrhagic shock (HS). To further quantify CitH3 in the NETs, we established a CitH3 specific enzyme-linked immunosorbent assay. Circulating CitH3 was found to be elevated only in LPSS but not in HS. Importantly, blood CitH3 was detected 30 minutes after LPS insult, and remained elevated for 24 hours (period of the highest mortality). Treatment of endotoxic mice with YW3-56, a peptidylarginine deiminase-2/4 inhibitor, significantly diminished levels of CitH3 in the blood. Interleukin-1β did not respond to LPS early, and interleukin-1β and interleukin-6 fluctuated although they responded to treatment. Procalcitonin reacted to LPS insult late. Compared to CitH3, these biomarkers were non-specifically induced in LPSS and HS. Collectively, our results demonstrate that YW3-56 protects animals from LPSS, and CitH3 is a reliable biomarker due to its early appearance, specificity, duration, and response to therapeutic intervention.Baihong PanHasan B. AlamWei ChongJames MobleyBaoling LiuQiufang DengYinjian LiangYanming WangEric ChenTianbing WangMuneesh TewariYongqing LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Baihong Pan Hasan B. Alam Wei Chong James Mobley Baoling Liu Qiufang Deng Yinjian Liang Yanming Wang Eric Chen Tianbing Wang Muneesh Tewari Yongqing Li CitH3: a reliable blood biomarker for diagnosis and treatment of endotoxic shock
description	Abstract Current biomarkers for sepsis are limited by their non-specificity, short half-life, and insensitive response to therapy. Recently, we have demonstrated that citrullinated histone H3(CitH3) is released into the blood from neutrophil extracellular traps(NETs) in response to severe infection, and CitH3 may be a potential biomarker for sepsis. In the present study, we found that NET components were released in mouse models of both lipopolysaccharide(LPS)-induced shock (LPSS) and hemorrhagic shock (HS). To further quantify CitH3 in the NETs, we established a CitH3 specific enzyme-linked immunosorbent assay. Circulating CitH3 was found to be elevated only in LPSS but not in HS. Importantly, blood CitH3 was detected 30 minutes after LPS insult, and remained elevated for 24 hours (period of the highest mortality). Treatment of endotoxic mice with YW3-56, a peptidylarginine deiminase-2/4 inhibitor, significantly diminished levels of CitH3 in the blood. Interleukin-1β did not respond to LPS early, and interleukin-1β and interleukin-6 fluctuated although they responded to treatment. Procalcitonin reacted to LPS insult late. Compared to CitH3, these biomarkers were non-specifically induced in LPSS and HS. Collectively, our results demonstrate that YW3-56 protects animals from LPSS, and CitH3 is a reliable biomarker due to its early appearance, specificity, duration, and response to therapeutic intervention.
format	article
author	Baihong Pan Hasan B. Alam Wei Chong James Mobley Baoling Liu Qiufang Deng Yinjian Liang Yanming Wang Eric Chen Tianbing Wang Muneesh Tewari Yongqing Li
author_facet	Baihong Pan Hasan B. Alam Wei Chong James Mobley Baoling Liu Qiufang Deng Yinjian Liang Yanming Wang Eric Chen Tianbing Wang Muneesh Tewari Yongqing Li
author_sort	Baihong Pan
title	CitH3: a reliable blood biomarker for diagnosis and treatment of endotoxic shock
title_short	CitH3: a reliable blood biomarker for diagnosis and treatment of endotoxic shock
title_full	CitH3: a reliable blood biomarker for diagnosis and treatment of endotoxic shock
title_fullStr	CitH3: a reliable blood biomarker for diagnosis and treatment of endotoxic shock
title_full_unstemmed	CitH3: a reliable blood biomarker for diagnosis and treatment of endotoxic shock
title_sort	cith3: a reliable blood biomarker for diagnosis and treatment of endotoxic shock
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0aab2b3818fa475fbc953f16e0260f02
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CitH3: a reliable blood biomarker for diagnosis and treatment of endotoxic shock

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