title: Albumin Homodimers in Patients with Cirrhosis: Clinical and Prognostic Relevance of a Novel Identified Structural Alteration of the Molecule.
abstract: 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.
authors: Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Italy.|Center for Applied Biomedical Research (C.R.B.A.), Alma Mater Studiorum University of Bologna, Italy.
authors: Maurizio
authors: M
authors: Baldassarre
authors: Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Italy.|Center for Applied Biomedical Research (C.R.B.A.), Alma Mater Studiorum University of Bologna, Italy.
authors: Marco
authors: M
authors: Domenicali
authors: Center for Applied Biomedical Research (C.R.B.A.), Alma Mater Studiorum University of Bologna, Italy.|Department of Pharmacology and Biotechnology, Alma Mater Studiorum University of Bologna, Italy.
authors: Marina
authors: M
authors: Naldi
authors: Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Italy.|Center for Applied Biomedical Research (C.R.B.A.), Alma Mater Studiorum University of Bologna, Italy.
authors: Maristella
authors: M
authors: Laggetta
authors: Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Italy.|Center for Applied Biomedical Research (C.R.B.A.), Alma Mater Studiorum University of Bologna, Italy.
authors: Ferdinando A
authors: FA
authors: Giannone
authors: Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Italy.
authors: Maurizio
authors: M
authors: Biselli
authors: Centralized Laboratory, S. Orsola-Malpighi University Hospital, Bologna, Italy.
authors: Daniela
authors: D
authors: Patrono
authors: Department of Pharmacology and Biotechnology, Alma Mater Studiorum University of Bologna, Italy.
authors: Carlo
authors: C
authors: Bertucci
authors: Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Italy.|Center for Applied Biomedical Research (C.R.B.A.), Alma Mater Studiorum University of Bologna, Italy.
authors: Mauro
authors: M
authors: Bernardi
authors: Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Italy.|Center for Applied Biomedical Research (C.R.B.A.), Alma Mater Studiorum University of Bologna, Italy.
authors: Paolo
authors: P
authors: Caraceni
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000097:blood* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020033:Protein Isoforms / Q000097:blood / Q000737:chemistry; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D000075462:Serum Albumin, Human / Q000737:chemistry*; D012720:Severity of Illness Index; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D020033:Protein Isoforms; D000075462:Serum Albumin, Human