Genetic variants of TRAF6 modulate peritoneal immunity and the risk of spontaneous bacterial peritonitis in cirrhosis: A combined prospective-retrospective study

Abstract Alterations of the innate immunity contribute to the development of spontaneous bacterial peritonitis (SBP) in liver cirrhosis. Given its role in immune signaling, antimicrobial function, and macrophage differentiation, we hypothesized that genetic polymorphisms of TRAF6 modulate the risk o...

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Autores principales:	Martina Mai, Sven Stengel, Eihab Al-Herwi, Jack Peter, Caroline Schmidt, Ignacio Rubio, Andreas Stallmach, Tony Bruns
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/615140608d3c41639bb71c3971c5953b
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spelling	oai:doaj.org-article:615140608d3c41639bb71c3971c5953b2021-12-02T16:07:45ZGenetic variants of TRAF6 modulate peritoneal immunity and the risk of spontaneous bacterial peritonitis in cirrhosis: A combined prospective-retrospective study10.1038/s41598-017-04895-z2045-2322https://doaj.org/article/615140608d3c41639bb71c3971c5953b2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04895-zhttps://doaj.org/toc/2045-2322Abstract Alterations of the innate immunity contribute to the development of spontaneous bacterial peritonitis (SBP) in liver cirrhosis. Given its role in immune signaling, antimicrobial function, and macrophage differentiation, we hypothesized that genetic polymorphisms of TRAF6 modulate the risk of SBP. Thus, we determined theTRAF6 haplotype in 432 patients with cirrhosis and ascites using the haplotype-tagging single nucleotide polymorphisms rs331457 and rs5030419. In addition, peritoneal macrophages were immunomagnetically isolated and characterized. Overall, 122 (28%) patients had an episode of SBP. In the combined prospective-retrospective analysis the frequency of SBP differed between the four haplotypes (P = 0.014) and was the highest in 102 patients carrying the rs331457 but not the rs5030419 variant, when compared to other haplotypes (odds ratio 1.95 [1.22–3.12]) or to the wild-type (odds ratio 1.71 [1.04–2.82]). This association was confirmed in multivariate logistic regression (adjusted odds ratio 2.00 [1.24–3.22]) and in prospective sensitivity analysis (hazard ratio 2.09 [1.08–4.07]; P = 0.03). The risk haplotype was associated with lower concentrations of the immune activation marker soluble CD87 in ascitic fluid and with a decreased expression of IL-6 and CXCL8 in isolated peritoneal macrophages. In conclusion, genetic polymorphisms of TRAF6 are associated with decreased peritoneal immune activation and an increased risk of SBP.Martina MaiSven StengelEihab Al-HerwiJack PeterCaroline SchmidtIgnacio RubioAndreas StallmachTony BrunsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Martina Mai Sven Stengel Eihab Al-Herwi Jack Peter Caroline Schmidt Ignacio Rubio Andreas Stallmach Tony Bruns Genetic variants of TRAF6 modulate peritoneal immunity and the risk of spontaneous bacterial peritonitis in cirrhosis: A combined prospective-retrospective study
description	Abstract Alterations of the innate immunity contribute to the development of spontaneous bacterial peritonitis (SBP) in liver cirrhosis. Given its role in immune signaling, antimicrobial function, and macrophage differentiation, we hypothesized that genetic polymorphisms of TRAF6 modulate the risk of SBP. Thus, we determined theTRAF6 haplotype in 432 patients with cirrhosis and ascites using the haplotype-tagging single nucleotide polymorphisms rs331457 and rs5030419. In addition, peritoneal macrophages were immunomagnetically isolated and characterized. Overall, 122 (28%) patients had an episode of SBP. In the combined prospective-retrospective analysis the frequency of SBP differed between the four haplotypes (P = 0.014) and was the highest in 102 patients carrying the rs331457 but not the rs5030419 variant, when compared to other haplotypes (odds ratio 1.95 [1.22–3.12]) or to the wild-type (odds ratio 1.71 [1.04–2.82]). This association was confirmed in multivariate logistic regression (adjusted odds ratio 2.00 [1.24–3.22]) and in prospective sensitivity analysis (hazard ratio 2.09 [1.08–4.07]; P = 0.03). The risk haplotype was associated with lower concentrations of the immune activation marker soluble CD87 in ascitic fluid and with a decreased expression of IL-6 and CXCL8 in isolated peritoneal macrophages. In conclusion, genetic polymorphisms of TRAF6 are associated with decreased peritoneal immune activation and an increased risk of SBP.
format	article
author	Martina Mai Sven Stengel Eihab Al-Herwi Jack Peter Caroline Schmidt Ignacio Rubio Andreas Stallmach Tony Bruns
author_facet	Martina Mai Sven Stengel Eihab Al-Herwi Jack Peter Caroline Schmidt Ignacio Rubio Andreas Stallmach Tony Bruns
author_sort	Martina Mai
title	Genetic variants of TRAF6 modulate peritoneal immunity and the risk of spontaneous bacterial peritonitis in cirrhosis: A combined prospective-retrospective study
title_short	Genetic variants of TRAF6 modulate peritoneal immunity and the risk of spontaneous bacterial peritonitis in cirrhosis: A combined prospective-retrospective study
title_full	Genetic variants of TRAF6 modulate peritoneal immunity and the risk of spontaneous bacterial peritonitis in cirrhosis: A combined prospective-retrospective study
title_fullStr	Genetic variants of TRAF6 modulate peritoneal immunity and the risk of spontaneous bacterial peritonitis in cirrhosis: A combined prospective-retrospective study
title_full_unstemmed	Genetic variants of TRAF6 modulate peritoneal immunity and the risk of spontaneous bacterial peritonitis in cirrhosis: A combined prospective-retrospective study
title_sort	genetic variants of traf6 modulate peritoneal immunity and the risk of spontaneous bacterial peritonitis in cirrhosis: a combined prospective-retrospective study
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/615140608d3c41639bb71c3971c5953b
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Genetic variants of TRAF6 modulate peritoneal immunity and the risk of spontaneous bacterial peritonitis in cirrhosis: A combined prospective-retrospective study

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