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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Format: | Article |
Language: | English |
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Elsevier
2020-07-01
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Series: | International Journal of Infectious Diseases |
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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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institution | Directory Open Access Journal |
issn | 1201-9712 |
language | English |
last_indexed | 2024-12-22T01:57:40Z |
publishDate | 2020-07-01 |
publisher | Elsevier |
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series | International Journal of Infectious Diseases |
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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