Specificity of B-type natriuretic peptide assays: Cross-reactivity with different BNP, NT-proBNP, and proBNP peptides

Amy K. Saenger, Olaia Rodriguez-Fraga, Ranka Ler, Jordi Ordonez-Llanos, Allan S Jaffe, Jens Peter Goetze, Fred S. Apple

Research output: Contribution to journalArticle

21 Citations (Scopus)

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. NTproBNP assays do not detect glycosylated forms of either NT-proBNP or proBNP. proBNP assays preferentially detect the BNP 1-32 peptide and have minimal crossreactivity 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.

Original languageEnglish (US)
Pages (from-to)351-358
Number of pages8
JournalClinical Chemistry
Volume63
Issue number1
DOIs
StatePublished - Jan 1 2017

Fingerprint

Brain Natriuretic Peptide
Assays
Peptides
Immunoassay
pro-brain natriuretic peptide (1-76)
Plasma (human)
Heart Failure

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Specificity of B-type natriuretic peptide assays : Cross-reactivity with different BNP, NT-proBNP, and proBNP peptides. / Saenger, Amy K.; Rodriguez-Fraga, Olaia; Ler, Ranka; Ordonez-Llanos, Jordi; Jaffe, Allan S; Goetze, Jens Peter; Apple, Fred S.

In: Clinical Chemistry, Vol. 63, No. 1, 01.01.2017, p. 351-358.

Research output: Contribution to journalArticle

Saenger, Amy K. ; Rodriguez-Fraga, Olaia ; Ler, Ranka ; Ordonez-Llanos, Jordi ; Jaffe, Allan S ; Goetze, Jens Peter ; Apple, Fred S. / Specificity of B-type natriuretic peptide assays : Cross-reactivity with different BNP, NT-proBNP, and proBNP peptides. In: Clinical Chemistry. 2017 ; Vol. 63, No. 1. pp. 351-358.
@article{506bc7ee80fb45f1b9e121404a80c87a,
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. NTproBNP assays do not detect glycosylated forms of either NT-proBNP or proBNP. proBNP assays preferentially detect the BNP 1-32 peptide and have minimal crossreactivity 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.",
author = "Saenger, {Amy K.} and Olaia Rodriguez-Fraga and Ranka Ler and Jordi Ordonez-Llanos and Jaffe, {Allan S} and Goetze, {Jens Peter} and Apple, {Fred S.}",
year = "2017",
month = "1",
day = "1",
doi = "10.1373/clinchem.2016.263749",
language = "English (US)",
volume = "63",
pages = "351--358",
journal = "Clinical Chemistry",
issn = "0009-9147",
publisher = "American Association for Clinical Chemistry Inc.",
number = "1",

}

TY - JOUR

T1 - Specificity of B-type natriuretic peptide assays

T2 - Cross-reactivity with different BNP, NT-proBNP, and proBNP peptides

AU - Saenger, Amy K.

AU - Rodriguez-Fraga, Olaia

AU - Ler, Ranka

AU - Ordonez-Llanos, Jordi

AU - Jaffe, Allan S

AU - Goetze, Jens Peter

AU - Apple, Fred S.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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. NTproBNP assays do not detect glycosylated forms of either NT-proBNP or proBNP. proBNP assays preferentially detect the BNP 1-32 peptide and have minimal crossreactivity 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.

AB - 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. NTproBNP assays do not detect glycosylated forms of either NT-proBNP or proBNP. proBNP assays preferentially detect the BNP 1-32 peptide and have minimal crossreactivity 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.

UR - http://www.scopus.com/inward/record.url?scp=85008512386&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85008512386&partnerID=8YFLogxK

U2 - 10.1373/clinchem.2016.263749

DO - 10.1373/clinchem.2016.263749

M3 - Article

C2 - 28062628

AN - SCOPUS:85008512386

VL - 63

SP - 351

EP - 358

JO - Clinical Chemistry

JF - Clinical Chemistry

SN - 0009-9147

IS - 1

ER -