TY - JOUR

T1 - Towards identification of novel putative biomarkers for infective endocarditis by serum proteomic analysis

AU - Snipsøyr, Magnus Giske

AU - Wiggers, Henrik

AU - Ludvigsen, Maja

AU - Stensballe, Allan

AU - Vorum, Henrik

AU - Poulsen, Steen Hvitfeldt

AU - Rasmussen, Lars Melholt

AU - Petersen, Eskild

AU - Honoré, Bent

N1 - Copyright © 2020. Published by Elsevier Ltd.

PY - 2020/7

Y1 - 2020/7

N2 - 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 and were studied by enzyme linked immunosorbent assay (ELISA). Proteomic analyses were conducted by 2-dimensional gel electrophoresis (2D-PAGE) and label free quantitative liquid chromatography - tandem mass spectrometry (LFQ LC-MS/MS). Controls 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.

AB - 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 and were studied by enzyme linked immunosorbent assay (ELISA). Proteomic analyses were conducted by 2-dimensional gel electrophoresis (2D-PAGE) and label free quantitative liquid chromatography - tandem mass spectrometry (LFQ LC-MS/MS). Controls 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.

KW - 2D-PAGE

KW - Biomarkers

KW - Infective endocarditis

KW - LFQ LC-MS/MS

KW - Non-infective endocarditis

KW - Serum proteomics

U2 - 10.1016/j.ijid.2020.02.026

DO - 10.1016/j.ijid.2020.02.026

M3 - Journal article

C2 - 32087365

VL - 96

SP - 73

EP - 81

JO - International Journal of Infectious Diseases

JF - International Journal of Infectious Diseases

SN - 1201-9712

ER -