The effect of glycosylation on plasma N-terminal proBNP-76 levels in patients with heart or renal failure

Nishikimi, Toshio; Ikeda, Masashi; Takeda, Yosuke; Ishimitsu, Toshihiko; Shibasaki, Ikuko; Fukuda, Hirotsugu; Kinoshita, Hideyuki; Nakagawa, Yasuaki; Kuwahara, Koichiro; Nakao, Kazuwa

doi:10.1136/heartjnl-2011-300102

Cited by 50 publications

(53 citation statements)

References 31 publications

(43 reference statements)

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“…3, C and E). This is supported by the work from Nishikimi et al, who recently reported that the ratios of glycosylated and nonglycosylated forms of plasma NT-proBNP are constant in all HF patients (NYHA class 1-4) (25 ).…”

Section: Discussionsupporting

confidence: 68%

Circulating Fragments of N-Terminal Pro–B-Type Natriuretic Peptides in Plasma of Heart Failure Patients

Foo

Wan

Schulz³

et al. 2013

Clinical Chemistry

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BACKGROUND The use of nonstandardized N-terminal pro–B-type natriuretic peptide (NT-proBNP) assays can contribute to the misdiagnosis of heart failure (HF). Moreover, there is yet to be established a common consensus regarding the circulating forms of NT-proBNP being used in current assays. We aimed to characterize and quantify the various forms of NT-proBNP in the circulation of HF patients. METHODS Plasma samples were collected from HF patients (n = 20) at rest and stored at −80 °C. NT-proBNP was enriched from HF patient plasma by use of immunoprecipitation followed by mass spectrometric analysis. Customized homogeneous sandwich AlphaLISA® immunoassays were developed and validated to quantify 6 fragments of NT-proBNP. RESULTS Mass spectrometry identified the presence of several N- and C-terminally processed forms of circulating NT-proBNP, with physiological proteolysis between Pro2-Leu3, Leu3-Gly4, Pro6-Gly7, and Pro75-Arg76. Consistent with this result, AlphaLISA immunoassays demonstrated that antibodies targeting the extreme N or C termini measured a low apparent concentration of circulating NT-proBNP. The apparent circulating NT-proBNP concentration was increased with antibodies targeting nonglycosylated and nonterminal epitopes (P < 0.05). CONCLUSIONS In plasma collected from HF patients, immunoreactive NT-proBNP was present as multiple N- and C-terminally truncated fragments of the full length NT-proBNP molecule. Immunodetection of NT-proBNP was significantly improved with the use of antibodies that did not target these terminal regions. These findings support the development of a next generation NT-proBNP assay targeting nonterminal epitopes as well as avoiding the central glycosylated region of this molecule.

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Section: Discussionsupporting

confidence: 68%

Circulating Fragments of N-Terminal Pro–B-Type Natriuretic Peptides in Plasma of Heart Failure Patients

Foo

Wan

Schulz³

et al. 2013

Clinical Chemistry

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“…In previous studies, the Roche Elecsys Gen I detection antibody (aa 39 -50) demonstrated poor cross-reactivity with glycosylated NT-proBNP and this was confirmed in our study (data not shown). A significant increase in plasma NTproBNP concentrations was noted following deglycosylation, suggesting that this assay measures only 20% of circulating NT-proBNP which corresponds to the nonglycosylated form (15,16 ). The Roche Elecsys NTproBNP Gen II assay also uses antibodies directed to the central glycosylated region (aa 42-46) and nearly all NTproBNP assays used clinically use Roche NT-proBNP I or NT-proBNP II antibodies which recognize residues in this highly glycosylated region.…”

Section: Discussionmentioning

confidence: 99%

Specificity of B-Type Natriuretic Peptide Assays: Cross-Reactivity with Different BNP, NT-proBNP, and proBNP Peptides

et al. 2017

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“…Clinicians should be aware that these detection platforms underestimate the concentration of circulating biomarker considerably. Some studies suggest that the underestimation might be up to 10-fold (19,35 ). Some recommend that future NT-proBNP platforms use deglycosylation of blood samples before assay.…”

Section: Nt-probnp Assaysmentioning

confidence: 99%

“…This study included a blend of chronic and acute HF patients. Reference limits also vary by age and sex of patients analyzed (35 ).…”

Section: Nt-probnp Assaysmentioning

confidence: 99%

Natriuretic Peptides and Analytical Barriers

Vasile

Jaffe

2017

Clinical Chemistry

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BACKGROUND:The natriuretic peptide system is an endocrine, autocrine and paracrine system that plays an important role in the maintenance of cardiovascular homeostasis. Biomarkers based on these peptides are important diagnostic and prognostic tools for myocardial function.CONTENT: Although natriuretic peptides were discovered more than 2 decades ago, their intricate and complex biology is associated with important questions not yet elucidated. The diversity of circulating forms of natriuretic peptides, the distinct expression of these forms in particular patients, and the heterogeneity of heart failure forms, along with specific assay-related and preanalytic issues, cause assays to be poorly harmonized.

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The effect of glycosylation on plasma N-terminal proBNP-76 levels in patients with heart or renal failure

Abstract: THE findings suggest that most endogenous plasma NT-BNP is glycosylated and therefore undetectable with the current assay system, and that the relative glycosylation level is increased by haemodialysis.

Cited by 50 publications

References 31 publications

Circulating Fragments of N-Terminal Pro–B-Type Natriuretic Peptides in Plasma of Heart Failure Patients

Circulating Fragments of N-Terminal Pro–B-Type Natriuretic Peptides in Plasma of Heart Failure Patients

Specificity of B-Type Natriuretic Peptide Assays: Cross-Reactivity with Different BNP, NT-proBNP, and proBNP Peptides

Natriuretic Peptides and Analytical Barriers

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