Towards identification of novel putative biomarkers for infective endocarditis by serum proteomic analysis

Introduction: Infective endocarditis (IE) has high mortality, partly due to delayed diagnosis. No biomarker can identify IE in patients with fever and clinical picture of infection. To find putative biomarkers we analyzed serum levels of two proteins found in cardiac valves, fibulin-1 (n = 696) and...

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Main Authors: Magnus Giske Snipsøyr, Henrik Wiggers, Maja Ludvigsen, Allan Stensballe, Henrik Vorum, Steen Hvitfeldt Poulsen, Lars Melholt Rasmussen, Eskild Petersen, Bent Honoré
Format: Article
Language:English
Published: Elsevier 2020-07-01
Series:International Journal of Infectious Diseases
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1201971220300849
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author Magnus Giske Snipsøyr
Henrik Wiggers
Maja Ludvigsen
Allan Stensballe
Henrik Vorum
Steen Hvitfeldt Poulsen
Lars Melholt Rasmussen
Eskild Petersen
Bent Honoré
author_facet Magnus Giske Snipsøyr
Henrik Wiggers
Maja Ludvigsen
Allan Stensballe
Henrik Vorum
Steen Hvitfeldt Poulsen
Lars Melholt Rasmussen
Eskild Petersen
Bent Honoré
author_sort Magnus Giske Snipsøyr
collection DOAJ
description Introduction: Infective endocarditis (IE) has high mortality, partly due to delayed diagnosis. No biomarker can identify IE in patients with fever and clinical picture of infection. To find putative biomarkers we analyzed serum levels of two proteins found in cardiac valves, fibulin-1 (n = 696) and osteoprotegerin (n = 689) among patients on clinical suspicion of IE. Proteomic analyses were performed in 24 patients with bacteremia, 12 patients with definite IE and 12 patients with excluded IE. Methods: Fibulin-1 and osteoprotegerin were studied by enzyme linked immunosorbent assay (ELISA). Proteomic analyses were conducted by 2-dimensional polyacrylamid gel electrophoresis (2D-PAGE) and label-free quantitative liquid chromatography - tandem mass spectrometry (LFQ LC-MS/MS). Controls for 2D 2D-PAGE and LFQ LC-MS/MS had bacteremia and excluded IE. Results: Osteoprotegerin levels were significantly increased in IE patients compared with non-IE patients. Fibulin-1 showed no difference. 2D-PAGE showed significant differences of 6 proteoforms: haptoglobin, haptoglobin-related protein, α-2-macroglobulin, apolipoprotein A-I and ficolin-3. LFQ LC-MS/MS analysis revealed significant level changes of 7 proteins: apolipoprotein L1, complement C1q subcomponent B and C, leukocyte immunoglobulin-like receptor subfamily A member 3, neuropilin-2, multimerin-1 and adiponectin. Conclusions: The concentration changes in a set of proteoforms/proteins suggest that stress and inflammation responses are perturbed in patients with IE compared to patients with bacteremia without IE.
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spelling doaj.art-ef2e5149eb1d464693131cc6d501e1842022-12-21T18:42:44ZengElsevierInternational Journal of Infectious Diseases1201-97122020-07-01967381Towards identification of novel putative biomarkers for infective endocarditis by serum proteomic analysisMagnus Giske Snipsøyr0Henrik Wiggers1Maja Ludvigsen2Allan Stensballe3Henrik Vorum4Steen Hvitfeldt Poulsen5Lars Melholt Rasmussen6Eskild Petersen7Bent Honoré8Department of Biomedicine, Aarhus University, Aarhus, Denmark; Department of Cardiology, Aarhus University Hospital, Skejby, Denmark; Department of Infectious Diseases, Aarhus University Hospital, Skejby, DenmarkDepartment of Cardiology, Aarhus University Hospital, Skejby, DenmarkDepartment of Biomedicine, Aarhus University, Aarhus, DenmarkDepartment of Health Science and Technology, Aalborg University, DenmarkDepartment of Clinical Medicine, Aalborg University, DenmarkDepartment of Cardiology, Aarhus University Hospital, Skejby, DenmarkDepartment of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, DenmarkDepartment of Infectious Diseases, Aarhus University Hospital, Skejby, DenmarkDepartment of Biomedicine, Aarhus University, Aarhus, Denmark; Department of Clinical Medicine, Aalborg University, Denmark; Corresponding author at: Department of Biomedicine, Aarhus University, Aarhus, Denmark, Ole Worms Allé 4, 8000 Aarhus C, Denmark.Introduction: Infective endocarditis (IE) has high mortality, partly due to delayed diagnosis. No biomarker can identify IE in patients with fever and clinical picture of infection. To find putative biomarkers we analyzed serum levels of two proteins found in cardiac valves, fibulin-1 (n = 696) and osteoprotegerin (n = 689) among patients on clinical suspicion of IE. Proteomic analyses were performed in 24 patients with bacteremia, 12 patients with definite IE and 12 patients with excluded IE. Methods: Fibulin-1 and osteoprotegerin were studied by enzyme linked immunosorbent assay (ELISA). Proteomic analyses were conducted by 2-dimensional polyacrylamid gel electrophoresis (2D-PAGE) and label-free quantitative liquid chromatography - tandem mass spectrometry (LFQ LC-MS/MS). Controls for 2D 2D-PAGE and LFQ LC-MS/MS had bacteremia and excluded IE. Results: Osteoprotegerin levels were significantly increased in IE patients compared with non-IE patients. Fibulin-1 showed no difference. 2D-PAGE showed significant differences of 6 proteoforms: haptoglobin, haptoglobin-related protein, α-2-macroglobulin, apolipoprotein A-I and ficolin-3. LFQ LC-MS/MS analysis revealed significant level changes of 7 proteins: apolipoprotein L1, complement C1q subcomponent B and C, leukocyte immunoglobulin-like receptor subfamily A member 3, neuropilin-2, multimerin-1 and adiponectin. Conclusions: The concentration changes in a set of proteoforms/proteins suggest that stress and inflammation responses are perturbed in patients with IE compared to patients with bacteremia without IE.http://www.sciencedirect.com/science/article/pii/S1201971220300849BiomarkersInfective endocarditisLFQ LC-MS/MSNon-infective endocarditisSerum proteomics2D-PAGE
spellingShingle Magnus Giske Snipsøyr
Henrik Wiggers
Maja Ludvigsen
Allan Stensballe
Henrik Vorum
Steen Hvitfeldt Poulsen
Lars Melholt Rasmussen
Eskild Petersen
Bent Honoré
Towards identification of novel putative biomarkers for infective endocarditis by serum proteomic analysis
International Journal of Infectious Diseases
Biomarkers
Infective endocarditis
LFQ LC-MS/MS
Non-infective endocarditis
Serum proteomics
2D-PAGE
title Towards identification of novel putative biomarkers for infective endocarditis by serum proteomic analysis
title_full Towards identification of novel putative biomarkers for infective endocarditis by serum proteomic analysis
title_fullStr Towards identification of novel putative biomarkers for infective endocarditis by serum proteomic analysis
title_full_unstemmed Towards identification of novel putative biomarkers for infective endocarditis by serum proteomic analysis
title_short Towards identification of novel putative biomarkers for infective endocarditis by serum proteomic analysis
title_sort towards identification of novel putative biomarkers for infective endocarditis by serum proteomic analysis
topic Biomarkers
Infective endocarditis
LFQ LC-MS/MS
Non-infective endocarditis
Serum proteomics
2D-PAGE
url http://www.sciencedirect.com/science/article/pii/S1201971220300849
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