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

Abstract

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.

Ficolin‐3 in chronic Chagas disease: Low serum levels associated with the risk of cardiac insufficiency

“…All these observations could indicate ficolin-3 as a potential biomarker for the severity of cardiac injury regardless of the aetiology of heart failure. The lower FCN3 gene expression profile in patients with heart failure65 and the downregulation of ficolin-3 in patients with infective endocarditis66 all corroborate the use of ficolin-3 as a biomarker of cardiac injury. Interestingly, no differences in ficolin-3 levels were found when comparing indeterminate and cardiac CD forms.…”

Native valve, prosthetic valve, and cardiac device-related infective endocarditis: A review and update on current innovative diagnostic and therapeutic strategies

“…Currently the detection of IE biomarkers is not being used in the clinic. Biomarkers indicating the presence of IE could be of great value for early diagnosis and several mass spectrometry approaches are aiming to detect IE by finding potential biomarkers ( Martin et al, 2020 ; Snipsoyr et al, 2020 ). One such biomarker is Osteoprotegerin, which could potentially be used to exclude IE in patients suspected to have IE ( Snipsoyr et al, 2020 ).…”

“…Biomarkers indicating the presence of IE could be of great value for early diagnosis and several mass spectrometry approaches are aiming to detect IE by finding potential biomarkers ( Martin et al, 2020 ; Snipsoyr et al, 2020 ). One such biomarker is Osteoprotegerin, which could potentially be used to exclude IE in patients suspected to have IE ( Snipsoyr et al, 2020 ). A major challenge is the verification of possible biomarkers due to inter-patient variability and the low sensitivity and specificity in blood samples, which can be attributed to high abundance of blood protein peptides.…”

Multimerin-1 and cancer: a review

“…In addition to cancer, MMRN1 is differentially expressed in other diseases including inflammation and bacterial and viral infections (186,(194)(195)(196)(197). Upregulation of MMRN1 has also been observed in injuries including septic shock-associated kidney injury (198) and in serum exosomes from burn patients (185).…”