title: Specificity of B-Type Natriuretic Peptide Assays: Cross-Reactivity with Different BNP, NT-proBNP, and proBNP Peptides.
abstract: BACKGROUND
  B-type natriuretic peptides (BNPs) are used clinically to diagnose and monitor heart failure and are present in the circulation as multiple proBNP-derived fragments. We investigated the specificity of BNP immunoassays with glycosylated and nonglycosylated BNP, N-terminal proBNP (NT-proBNP), and proBNP peptides to probe the cross-reactivity of each assay.
  
  
  METHODS
  Nine B-type natriuretic peptides were studied,including synthetic and recombinant BNP (Shionogi, Scios, Mayo), human and synthetic glycosylated and nonglycosylated NT-proBNP (HyTest, Roche Diagnostics), and human glycosylated and nonglycosylated proBNP (HyTest, Scios). Five BNP [Abbott, Abbott POC, Alere, Beckman Coulter, Siemens (Centaur)], 9 NT-proBNP [Ortho-Clinical Diagnostics, Roche, Response, bioMerieux, Siemens (Dimension, Immulite, Stratus CS), Mitsubishi] and 3 research-use-only proBNP immunoassays [Biosite (Alere), Bio-Rad, Goetze] were evaluated. Specificity was assessed by calculating the recovery between baseline and peptide-spiked human plasma pools at target concentrations of 100 ng/L BNP, 300 ng/L proBNP, or 450 ng/L NT-proBNP. All assays were performed in duplicate.
  
  
  RESULTS
  BNP and NT-proBNP assays demonstrated substantial cross-reactivity with proBNP peptides. NT-proBNP assays do not detect glycosylated forms of either NT-proBNP or proBNP. proBNP assays preferentially detect the BNP 1-32 peptide and have minimal cross-reactivity with BNP peptides and glycosylated proBNP.
  
  
  CONCLUSIONS
  BNP or NT-proBNP results are not transferable among the current existing immunoassays owing to their differences in cross-reactivity and ability to detect various glycosylated forms of proBNP-derived fragments. Opportunities remain to standardize and harmonize BNP and NT-proBNP assays, as well as to develop specific proBNP assays, to widen their clinical scope of use.
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Saenger
authors.affiliation: Laboratory Medicine Department, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Olaia
authors.initials: O
authors.lastname: Rodriguez-Fraga
authors.affiliation: Minneapolis Medical Research Foundation, Minneapolis, MN.
authors.forename: Ranka
authors.initials: R
authors.lastname: Ler
authors.affiliation: IIB-Hospital de la Santa Creu i Sant Pau and Universitat Autònoma, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Ordonez-Llanos
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Mayo Clinic, Rochester, MN.
authors.forename: Allan S
authors.initials: AS
authors.lastname: Jaffe
authors.affiliation: Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Jens Peter
authors.initials: JP
authors.lastname: Goetze
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN; apple004@umn.edu.|Department of Laboratory Medicine and Pathology, Hennepin County Medical Center, Minneapolis, MN.
authors.forename: Fred S
authors.initials: FS
authors.lastname: Apple
mesh_terms: D003429:Cross Reactions; D006801:Humans; D007118:Immunoassay; D020097:Natriuretic Peptide, Brain / Q000097:blood*
chemical_list: D020097:Natriuretic Peptide, Brain