title: Human Neutrophil Lipocalin as a Superior Diagnostic Means To Distinguish between Acute Bacterial and Viral Infections.
abstract: The distinction between causes of acute infections is a major clinical challenge. Current biomarkers, however, are not sufficiently accurate. Human neutrophil lipocalin (HNL) concentrations in serum or whole blood activated by formyl-methionine-leucine-phenylalanine (fMLP) were shown to distinguish acute infections of bacterial or viral cause with high accuracy. The aim was therefore to compare the clinical performance of HNL with currently used biomarkers. Seven hundred twenty-five subjects (144 healthy controls and 581 patients with signs and symptoms of acute infections) were included in the study. C-reactive protein (CRP), the expression of CD64 on neutrophils, procalcitonin (PCT), and blood neutrophil counts were measured by established techniques, and HNL concentrations were measured in whole-blood samples after activation with fMLP. All tested biomarkers were elevated in bacterial as opposed to viral infections (P < 0.001). CRP, PCT, and CD64 expression in neutrophils was elevated in viral infections compared to healthy controls (P < 0.001). In the distinction between healthy controls and patients with bacterial infections, the areas under the receiver operating characteristic (ROC) curves were >0.85 for all biomarkers, whereas for the distinction between bacterial and viral infections, only HNL concentration in fMLP-activated whole blood showed an area under the ROC curve (AUROC) of >0.90 and superior clinical performance. The clinical performance of HNL in fMLP-activated whole blood was superior to current biomarkers and similar to previous results of HNL in serum. The procedure can be adopted for point-of-care testing with response times of <15 min.
authors.affiliation: Department of Medical Sciences, Section of Clinical Chemistry, Uppsala University, Uppsala, Sweden per.venge@medsci.uu.se.
authors.forename: Per
authors.identifier: http://orcid.org/0000-0001-5863-790X
authors.initials: P
authors.lastname: Venge
authors.affiliation: Department of Medical Sciences, Section of Clinical Chemistry, Uppsala University, Uppsala, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Douhan-Håkansson
authors.affiliation: Department of Medical Sciences, Section of Clinical Chemistry, Uppsala University, Uppsala, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Garwicz
authors.affiliation: Department of Medical Sciences, Section of Clinical Chemistry, Uppsala University, Uppsala, Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Peterson
authors.affiliation: Department of Medical Sciences, Section of Clinical Chemistry, Uppsala University, Uppsala, Sweden.
authors.forename: Shengyuan
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Uppsala, Sweden.
authors.forename: Karlis
authors.initials: K
authors.lastname: Pauksen
mesh_terms: D000208:Acute Disease; D000209:Acute-Phase Proteins / Q000032:analysis; D000328:Adult; D000368:Aged; D001424:Bacterial Infections / Q000175:diagnosis* / Q000276:immunology; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D000067716:Point-of-Care Testing; D011518:Proto-Oncogene Proteins / Q000097:blood*; D012372:ROC Curve; D017452:Receptors, IgG / Q000032:analysis; D012680:Sensitivity and Specificity; D014777:Virus Diseases / Q000175:diagnosis* / Q000276:immunology
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D017452:Receptors, IgG; D002097:C-Reactive Protein