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Inhibition of glutamine synthetase in monocytes from patients with acute-on-chronic liver failure resuscitates their antibacterial and inflammatory capacity

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  • Contributors SvdM, HK and JvP conceptualised and planned the study. HK, JdP and SvdM wrote the protocol. HK and JdP performed the flow cytometry, monocyte functional studies, gene expression and multiplex cytokine assays. AT, RFA and SDG assisted with the Incucyte experiments. LM documented the clinical patient information. MVH and TR performed immunohistochemistry experiments. BG, DC, MB and S-MF provided support for the metabolic aspects of the study. JvP performed the RNA sequence pathway identification, the hierarchic clustering and statistical analysis. RJ, GM, RPM, TG, DC, FN, WL, LV and SvdM recruited and cared for the patients. HK and SvdM wrote the manuscript.

  • Funding This work was supported by internal funding from the UZ Leuven (KOOR) and KU Leuven (C1) as well as by the FWO and Gilead Sciences.

  • Competing interests SvdM, FN and DC are recipients of Flanders fund for scientific research (FWO fundamenteel-klinisch mandaat). RJ has research collaborations with Yaqrit and Takeda. RJ is the inventor of OPA, which has been patented by UCL and licensed to Mallinckrodt. He is also the founder of a UCL spin out, Yaqrit Limited, Ammun Limited and Cyberliver Limited.

  • Ethics approval Medical Ethics Committee (KU Leuven/UZ Leuven; S54588).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The RNA sequencing data will become available at the Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/) under accession number GSE93265.

  • Patient consent for publication Not required.

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Footnotes

  • Contributors SvdM, HK and JvP conceptualised and planned the study. HK, JdP and SvdM wrote the protocol. HK and JdP performed the flow cytometry, monocyte functional studies, gene expression and multiplex cytokine assays. AT, RFA and SDG assisted with the Incucyte experiments. LM documented the clinical patient information. MVH and TR performed immunohistochemistry experiments. BG, DC, MB and S-MF provided support for the metabolic aspects of the study. JvP performed the RNA sequence pathway identification, the hierarchic clustering and statistical analysis. RJ, GM, RPM, TG, DC, FN, WL, LV and SvdM recruited and cared for the patients. HK and SvdM wrote the manuscript.

  • Funding This work was supported by internal funding from the UZ Leuven (KOOR) and KU Leuven (C1) as well as by the FWO and Gilead Sciences.

  • Competing interests SvdM, FN and DC are recipients of Flanders fund for scientific research (FWO fundamenteel-klinisch mandaat). RJ has research collaborations with Yaqrit and Takeda. RJ is the inventor of OPA, which has been patented by UCL and licensed to Mallinckrodt. He is also the founder of a UCL spin out, Yaqrit Limited, Ammun Limited and Cyberliver Limited.

  • Ethics approval Medical Ethics Committee (KU Leuven/UZ Leuven; S54588).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The RNA sequencing data will become available at the Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/) under accession number GSE93265.

  • Patient consent for publication Not required.

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