title: Detection of procalcitonin (PCT) in healthy controls and patients with local infection by a sensitive ILMA.
abstract: BACKGROUND
  Procalcitonin (PCT) is an established marker for severe systemic bacterial infection and sepsis. So far the relevance of PCT in healthy individuals or patients with local infections is unclear due to the lack of highly sensitive assays. The aim of our study was the characterization of a new sensitive PCT assay, the establishment of reference values and the assessment of diagnostic accuracy.
  
  
  METHODS
  We assessed PCT values in 522 patients with different infectious and non infectious conditions and 410 healthy controls by a new coated tube sandwich chemiluminescence assay B.R.A.H.M.S ProCa-S (2 step assay, time to result 2.5 hours).
  
  
  RESULTS
  The lower detection limit was 6.0 ng/L, with a functional assay sensitivity below 7 ng/L. Samples above 250 ng/L gave excellent correlation to the LUMItest PCT (r = 0.98, p < 0.0001). There was no high dose hook effect up to a concentration of 21,300 ng/L. The 410 healthy controls had a median concentration of 12.7 ng/L (95% CI: 12.6-14.7 ng/L). 65 controls had non-detectable PCT values (defined as 5 ng/L). The 2.5th percentile of the normal population was 5 ng/L and the 97.5th percentile was 46.7 ng/L. ROC plot analysis resulted in an area under the curve (AUC) of 0.90. The optimal decision threshold was at 50 ng/L, with a sensitivity for infection of 77.8% and a specificity of 98.5% (positive predictive value 97.7%, negative predictive value 84.9%). There was a highly significant (p < 0.0001) difference in the PCT median between healthy individuals and patients with infections (e.g. pneumonia, peritonitis) but not non-infectious controls (e.g. pregnancy, autoimmune disease).
  
  
  CONCLUSIONS
  The new PCT assay is 30 times more sensitive than the established routine assay LUMItest PCT, thus allowing for the first time PCT detection in healthy individuals. First results indicate that the assay is suitable to differentiate local bacterial infections from other non-infectious diseases.
authors.affiliation: Research Department, B.R.A.H.M.S. AG, Biotechnology Centre Hennigsdorf/Berlin, Germany. n.morgenthaler@brahms.de
authors.forename: Nils G
authors.initials: NG
authors.lastname: Morgenthaler
authors.forename: Joachim
authors.initials: J
authors.lastname: Struck
authors.forename: Christina
authors.initials: C
authors.lastname: Fischer-Schulz
authors.forename: Elke
authors.initials: E
authors.lastname: Seidel-Mueller
authors.forename: Wilfried
authors.initials: W
authors.lastname: Beier
authors.forename: Andreas
authors.initials: A
authors.lastname: Bergmann
mesh_terms: D000328:Adult; D001064:Appendicitis / Q000097:blood / Q000175:diagnosis; D015415:Biomarkers / Q000097:blood; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D005260:Female; D005335:Fever of Unknown Origin / Q000097:blood; D006801:Humans; D007239:Infections / Q000097:blood / Q000175:diagnosis*; D008163:Luminescent Measurements; D008171:Lung Diseases / Q000097:blood; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D011498:Protein Precursors / Q000097:blood*; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000175:diagnosis; D012016:Reference Values; D015203:Reproducibility of Results; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000175:diagnosis; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide