Abstract 4361616: Deglycosylation Enhances Performance of Soluble Urokinase Plasminogen Activator Receptor (suPAR) Levels for Acute Decompensated Heart Failure Diagnosis

Introduction: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker associated with incident acute heart failure. However, its diagnostic utility may be limited by N-linked glycosylation, which can hinder antibody recognition in ELISA. We investigated whether enzymatic removal of glycosylation improves suPAR’s diagnostic performance for acute decompensated heart failure (ADHF). Methods: Plasma samples from patients presenting to the emergency department with undifferentiated acute breathlessness (n = 103) were treated with deglycosylation enzyme (PNGase F) to remove suPAR N-linked glycosylation. suPAR concentrations were measured using the CE-marked suPARnostic ELISA (Virogates). The percentage change in paired enzyme-treated and non-treated suPAR concentrations was assessed using the Mann-Whitney U test. Diagnostic performance of non-treated vs deglycosylated suPAR was evaluated by Receiver Operating Characteristic (ROC)-AUC analysis (SPSS) and compared to NT-proBNP (Roche Cobas). Results: Of the 103 patients, 53 (51.4%) were diagnosed with ADHF and 50 (48.5%) with non-HF causes (pneumonia, COPD). Non-treated suPAR concentrations were higher in ADHF (4.5 ng/mL, IQR: 3.4-5.8) compared to non-HF breathless patients (3.2 ng/mL, IQR: 2.3-3.9) (p<0.001). Enzymatic treatment increased suPAR concentrations in all patients, but the increment was significantly greater in ADHF (median increase 39%, IQR 34-44) compared to non-HF (median increase 24%, IQR: 13-35) (p=0.002). ROC-AUC analyses revealed that deglycosylated suPAR (AUC = 0.850, 95% CI 0.752-0.947) was better at discriminating ADHF compared to non-treated suPAR (AUC = 0.765, 95% CI 0.649-0.882), and performance was comparable to that of NT-proBNP (AUC = 0.890, 95% CI 0.799-0.982) (p = 0.21). Conclusion: Glycosylation masks diagnostically relevant suPAR epitopes in the current ELISA, impairing its discriminative performance for ADHF. Further evaluation is needed to establish diagnostic value of deglycosylated suPAR levels in complementary with current cardiac markers.