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Albumin Homodimers in Patients with Cirrhosis: Clinical and Prognostic Relevance of a Novel Identified Structural Alteration of the Molecule

Decompensated cirrhosis is associated to extensive post-transcriptional changes of human albumin (HA). This study aims to characterize the occurrence of HA homodimerization in a large cohort of patients with decompensated cirrhosis and to evaluate its association with clinical features and prognosis...

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Autores principales: Baldassarre, Maurizio, Domenicali, Marco, Naldi, Marina, Laggetta, Maristella, Giannone, Ferdinando A., Biselli, Maurizio, Patrono, Daniela, Bertucci, Carlo, Bernardi, Mauro, Caraceni, Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5080612/
https://www.ncbi.nlm.nih.gov/pubmed/27782157
http://dx.doi.org/10.1038/srep35987
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author Baldassarre, Maurizio
Domenicali, Marco
Naldi, Marina
Laggetta, Maristella
Giannone, Ferdinando A.
Biselli, Maurizio
Patrono, Daniela
Bertucci, Carlo
Bernardi, Mauro
Caraceni, Paolo
author_facet Baldassarre, Maurizio
Domenicali, Marco
Naldi, Marina
Laggetta, Maristella
Giannone, Ferdinando A.
Biselli, Maurizio
Patrono, Daniela
Bertucci, Carlo
Bernardi, Mauro
Caraceni, Paolo
author_sort Baldassarre, Maurizio
collection PubMed
description Decompensated cirrhosis is associated to extensive post-transcriptional changes of human albumin (HA). This study aims to characterize the occurrence of HA homodimerization in a large cohort of patients with decompensated cirrhosis and to evaluate its association with clinical features and prognosis. HA monomeric and dimeric isoforms were identified in peripheral blood by using a HPLC-ESI-MS technique in 123 cirrhotic patients hospitalized for acute decompensation and 50 age- and sex-comparable healthy controls. Clinical and biochemical parameters were recorded and patients followed up to one year. Among the monomeric isoforms identified, the N- and C-terminal truncated and the native HA underwent homodimerization. All three homodimers were significantly more abundant in patients with cirrhosis, acute-on-chronic liver failure and correlate with the prognostic scores. The homodimeric N-terminal truncated isoform was independently associated to disease complications and was able to stratify 1-year survival. As a result of all these changes, the monomeric native HA was significantly decreased in patients with cirrhosis, being also associated with a poorer prognosis. In conclusion homodimerization is a novel described structural alteration of the HA molecule in decompensated cirrhosis and contributes to the progressive reduction of the monomeric native HA, the only isoform provided of structural and functional integrity.
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spelling pubmed-50806122016-10-31 Albumin Homodimers in Patients with Cirrhosis: Clinical and Prognostic Relevance of a Novel Identified Structural Alteration of the Molecule Baldassarre, Maurizio Domenicali, Marco Naldi, Marina Laggetta, Maristella Giannone, Ferdinando A. Biselli, Maurizio Patrono, Daniela Bertucci, Carlo Bernardi, Mauro Caraceni, Paolo Sci Rep Article Decompensated cirrhosis is associated to extensive post-transcriptional changes of human albumin (HA). This study aims to characterize the occurrence of HA homodimerization in a large cohort of patients with decompensated cirrhosis and to evaluate its association with clinical features and prognosis. HA monomeric and dimeric isoforms were identified in peripheral blood by using a HPLC-ESI-MS technique in 123 cirrhotic patients hospitalized for acute decompensation and 50 age- and sex-comparable healthy controls. Clinical and biochemical parameters were recorded and patients followed up to one year. Among the monomeric isoforms identified, the N- and C-terminal truncated and the native HA underwent homodimerization. All three homodimers were significantly more abundant in patients with cirrhosis, acute-on-chronic liver failure and correlate with the prognostic scores. The homodimeric N-terminal truncated isoform was independently associated to disease complications and was able to stratify 1-year survival. As a result of all these changes, the monomeric native HA was significantly decreased in patients with cirrhosis, being also associated with a poorer prognosis. In conclusion homodimerization is a novel described structural alteration of the HA molecule in decompensated cirrhosis and contributes to the progressive reduction of the monomeric native HA, the only isoform provided of structural and functional integrity. Nature Publishing Group 2016-10-26 /pmc/articles/PMC5080612/ /pubmed/27782157 http://dx.doi.org/10.1038/srep35987 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Baldassarre, Maurizio
Domenicali, Marco
Naldi, Marina
Laggetta, Maristella
Giannone, Ferdinando A.
Biselli, Maurizio
Patrono, Daniela
Bertucci, Carlo
Bernardi, Mauro
Caraceni, Paolo
Albumin Homodimers in Patients with Cirrhosis: Clinical and Prognostic Relevance of a Novel Identified Structural Alteration of the Molecule
title Albumin Homodimers in Patients with Cirrhosis: Clinical and Prognostic Relevance of a Novel Identified Structural Alteration of the Molecule
title_full Albumin Homodimers in Patients with Cirrhosis: Clinical and Prognostic Relevance of a Novel Identified Structural Alteration of the Molecule
title_fullStr Albumin Homodimers in Patients with Cirrhosis: Clinical and Prognostic Relevance of a Novel Identified Structural Alteration of the Molecule
title_full_unstemmed Albumin Homodimers in Patients with Cirrhosis: Clinical and Prognostic Relevance of a Novel Identified Structural Alteration of the Molecule
title_short Albumin Homodimers in Patients with Cirrhosis: Clinical and Prognostic Relevance of a Novel Identified Structural Alteration of the Molecule
title_sort albumin homodimers in patients with cirrhosis: clinical and prognostic relevance of a novel identified structural alteration of the molecule
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5080612/
https://www.ncbi.nlm.nih.gov/pubmed/27782157
http://dx.doi.org/10.1038/srep35987
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