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Review
. 2018 Mar;123(1):1-8.
doi: 10.1080/03009734.2017.1420112. Epub 2018 Feb 23.

Human Neutrophil Lipocalin (HNL) as a Biomarker of Acute Infections

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Free PMC article
Review

Human Neutrophil Lipocalin (HNL) as a Biomarker of Acute Infections

Per Venge. Ups J Med Sci. .
Free PMC article

Abstract

The early and accurate discrimination between bacterial and viral causes of acute infections is the key to a better use of antibiotics and will help slow down the fast-growing resistance to commonly used antibiotics. This discrimination is in the vast majority of cases possible to achieve by blood assay of the biomarker human neutrophil lipocalin (HNL), which we showed to be uniquely increased in patients suffering from bacterial infections. In serum, sensitivities and specificities of >90% are achieved in both adults and children. In order to eliminate the need to produce serum, a whole-blood assay with an assay time of <10 min was developed in which blood neutrophils are activated to release HNL. The diagnostic accuracy of this assay also showed sensitivities and specificities of >90% in most infectious diseases and was clearly superior to contemporary assays such as blood neutrophil counts, C-reactive protein, procalcitonin, and expression of CD64 on blood neutrophils. This format lends itself to the development of a point-of-care HNL assay and will be a major step forward to accomplish the goal of accurately diagnosing patients with symptoms of acute infections within 10 min at the emergency room or at the doctor's office.

Keywords: Clinical chemistry; immunoassays; infectious diseases.

Figures

Figure 1.
Figure 1.
(a) Serum concentrations of HNL as measured by radioimmunoassay in patients with verified bacterial or viral cause of their acute infection. The horizontal line indicates +3 SD of the upper level of healthy non-infected subjects. Also shown in the figure are the sensitivity and specificity of HNL in the discrimination between bacterial and viral infections. (b) ROC curve analysis of the results of serum HNL and plasma CRP measurements shown in Figure 1a. The areas under the ROC curves (AuROC) are given in the figure.
Figure 2.
Figure 2.
(a) Serum concentrations of dimeric HNL measured by our specific ELISA in patients with acute infections and in healthy non-infected controls. (b) ROC curve analysis of the results of serum HNL and plasma CRP and neutrophil counts in the patients shown in Figure 2(a).
Figure 3.
Figure 3.
Results of measuring HNL in serum, plasma, or after whole-blood activation. The diagnostic accuracy as defined by specificity + sensitivity/2 is given for the different measurements.
Figure 4.
Figure 4.
A ROC curve analysis of HNL after whole-blood activation in comparison with plasma concentrations of CRP and procalcitonin. Patients had symptoms of respiratory infections, and their infections were objectively verified by microbiological testing. The AuROCs are given in the figure.
None
Per Venge and his collaborators have been awarded the €1 million EU prize, the ‘Horizon Prize for better use of antibiotics’. This review summarizes how their combined research efforts have led to a unique solution to reliably detect bacterial infections.

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