title: Distinction between bacterial and viral infections by serum measurement of human neutrophil lipocalin (HNL) and the impact of antibody selection.
abstract: The distinction between acute infections of bacterial or viral causes is clinically important, but often very difficult even for experienced doctors. Previous studies indicated that serum measurements of HNL (Human Neutrophil Lipocalin) might be a superior diagnostic means in this regard, but also indicated that the antibody conformation of the HNL assay might have an impact on the diagnostic performance. The aim of the present report was to examine this further.
  
  
  METHODS
  Several different (n=24) HNL ELISA assays were developed using different combinations of monoclonal and polyclonal HNL antibodies. Sera were collected from healthy persons (n=188) and from 155 patients with acute infections before any antibiotics treatment. The patients were diagnosed as having bacterial (n=69) or viral causes (n=86) of their infections. Plasma and serum were also examined by Western blotting using HNL-specific polyclonal antibodies.
  
  
  RESULTS
  The optimal assay format for the distinction between bacterial and viral infection resulted in an area under the receiver operating characteristics curve (AuROC) for S-HNL of 0.98. (95% CI 0.94-1.00) as compared to 0.83 (0.76-0.88) for blood neutrophil counts and 0.69 (0.61-0.76) for S-CRP. Results also showed that different assay formats of HNL identified monomeric and dimeric HNL differently, the monomeric HNL being elevated in viral infections and the dimeric HNL being elevated in bacterial infections.
  
  
  CONCLUSIONS
  We conclude that serum measurement of HNL is a superior diagnostic means to distinguish between acute infections caused by bacteria or virus. For optimal clinical performance the immunoassay should address conformational epitopes in the dimeric HNL.
authors.affiliation: Changchun Brother Biotech Co., Ltd., Changchun 130062, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Laboratory Department of the First Affiliated Hospital of Jilin University, Changchun 130021, China.
authors.forename: Huang
authors.initials: H
authors.lastname: Jing
authors.affiliation: Laboratory Department of the 208th Hospital of PLA, Changchun 30000, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Hongtao
authors.affiliation: Laboratory Department of the 208th Hospital of PLA, Changchun 30000, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Furong
authors.affiliation: Laboratory Department of the First Affiliated Hospital of Jilin University, Changchun 130021, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yuting
authors.affiliation: Department of Medical Sciences, University of Uppsala, Uppsala, Sweden.
authors.forename: Shengyuan
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Medical Sciences, University of Uppsala, Uppsala, Sweden. Electronic address: per.venge@medsci.uu.se.
authors.forename: Per
authors.initials: P
authors.lastname: Venge
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D019540:Area Under Curve; D001424:Bacterial Infections / Q000097:blood / Q000175:diagnosis* / Q000382:microbiology; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005260:Female; D006801:Humans; D054834:Lipocalins / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D055503:Protein Multimerization; D012372:ROC Curve; D015854:Up-Regulation; D014777:Virus Diseases / Q000097:blood / Q000175:diagnosis* / Q000821:virology; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D000939:Epitopes; D054834:Lipocalins
keywords: Acute Infection; CRP; Diagnosis; Lipocalin; Neutrophil