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Proteomic evidence of bacterial peptide translocation in afebrile patients with cirrhosis and ascites

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Abstract

Bacterial translocation in patients with cirrhosis induces a marked proinflammatory activity that may be different against viable bacteria or bacterial products. The aim of this study is to identify new markers of bacterial translocation by investigating bacterial-driven peptides and correlate their presence with the inflammatory response. Patients with cirrhosis and ascites were included. An analysis by two-dimensional polyacrylamide gel electrophoresis of ascitic fluid total protein from patients (n = 47) and from frequently detected bacterial strains was performed. Two-dimensional maps were digitally compared. The identification of possible markers was performed by mass spectrometry. TNF-α, IFN-γ, IL-12, nitric oxide, and proteins of the complement and lipopolysaccharide-binding protein levels were measured in ascitic fluid samples of patients by enzyme-linked immunosorbent assay. Patients were distributed according to the presence (group I, n = 16) and absence (group II, n = 31) of serum and ascitic fluid bacterial DNA. Among clinical and analytical differences between groups, only mean arterial pressure was significantly higher in patients from group II. Identified bacterial peptides were associated with bacterial protection against immune defenses and included glyceraldehyde-3-phosphate dehydrogenase A, Porin OmpC, and HSP60. Eight patients from group I also showed bacterial peptides, whereas none from group II did. All studied mediators of immune activation were significantly higher in patients with bacterial DNA than in patients without bacterial DNA. TNF-α, IFN-γ, and proteins of the complement were significantly increased in patients with bacterial peptides versus those without bacterial peptides. Bacterial peptide translocation is present in the ascitic fluid of a subgroup of patients with advanced cirrhosis and is associated with an increased immune response.

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Funding

This study was funded by grants CP05/005, PI05/1784, and PI06/1453 from Instituto de Salud Carlos III, Madrid, Spain. Rocío Caño is recipient of a grant by Fundación FCVI–HGUA, Alicante, Spain.

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The authors declare that they have no conflicting interests related to this study.

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Authors and Affiliations

  1. Unidad Hepática, Hospital General Universitario, Avda. Pintor Baeza 12, 03010, Alicante, Spain

    Rocío Caño, Sonia Pascual, Pablo Bellot, Claudia Barquero, Miguel Pérez-Mateo, José Such & Rubén Francés

  2. Servicio de Farmacología Clínica, Hospital General Universitario, Alicante, Spain

    Lucía Llanos & Pedro Zapater

  3. CIBERehd, Instituto de Salud Carlos III, Madrid, Spain

    Pedro Zapater, Sonia Pascual, José Such & Rubén Francés

Authors
  1. Rocío Caño
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  2. Lucía Llanos
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  3. Pedro Zapater
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  4. Sonia Pascual
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  5. Pablo Bellot
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  6. Claudia Barquero
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  7. Miguel Pérez-Mateo
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  8. José Such
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  9. Rubén Francés
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Corresponding authors

Correspondence to José Such or Rubén Francés.

Additional information

R. Francés and J. Such contributed equally to the design and development of this investigation.

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Caño, R., Llanos, L., Zapater, P. et al. Proteomic evidence of bacterial peptide translocation in afebrile patients with cirrhosis and ascites. J Mol Med 88, 487–495 (2010). https://doi.org/10.1007/s00109-009-0582-9

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  • DOI: https://doi.org/10.1007/s00109-009-0582-9

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