Macro-pro-B-type natriuretic peptide (proBNP) and hidden macro-N-terminal proBNP: Case report

作者：Nakagawa Yasuaki; Nishikimi Toshio; Sakai Hiroshi; Ohno Seiko; Kinoshita Hideyuki; Inazumi Hideaki; Moriuchi Kenji; Kuwahara Koichiro; Horie Minoru; Kimura Takeshi

来源：Clinical Biochemistry, 2018, 52: 148-152.

DOI：10.1016/j.clinbiochem.2017.10.019

• BNP
• proBNP
• Macro-proBNP
• Macro-N-terminal proBNP

B-type natriuretic peptide (BNP) is a cardiac hormone widely used as a biomarker for heart failure. Here, we present the first report of extremely high levels of immunoreactive BNP caused by formation of macro-proBNP.
A 70-year-old woman with left ventricular hypertrophy and normal systolic function presented with extremely high plasma levels of BNP (35,374 pg/ml) and N-terminal proBNP (NT-proBNP; 30,600 pg/ml). Our recently developed proBNP immunoassay showed that nearly 100% of her immunoreactive BNP was proBNP. Polyethylene glycol precipitation tests reported extremely low BNP recovery (1.3%), while protein G addition tests also reported a remarkably low BNP fraction (3.3%). Gel filtration chromatography with normal elution buffer combined with BNP immunoassays showed a BNP peak with a retention time slightly shorter than that of IgG. With acidic elution buffer (pH 3.0), however this peak disappeared and a new BNP peak consistent with glycosylated human proBNP appeared. These results suggest that in this case most BNP immunoreactivity consisted of macro-proBNP, which is an immune complex composed of proBNP and an anti-proBNP autoantibody. Gel filtration chromatography combined with NT-proBNP immunoassays revealed that the NT-proBNP assay cross-reacts with both the proBNP-IgG complex and proBNP. In addition, with acidic buffer, a new large peak appeared with a retention time the same as that of glycosylated NT-proBNP.
These results suggest spuriously high levels of BNP and NT-proBNP are caused by macro-proBNP. Macro-NT-proBNP is not detected by the currently available NT-proBNP assay system.

• 出版日期2018-2