An automatic chemiluminescence immunoassay for a novel biomarker NT-IGFBP-4: analytical performance and clinical relevance in heart failure
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Shuzheng Cao
,
Xin Shu
and
Zhenlu Zhang
Abstract
Objectives
Insulin-like growth factor binding protein-4 (IGFBP-4) fragments are reported as emerging biomarkers for cardiovascular disease (CVD) risk assessment. To ensure data reliability and improve clinical application, the first automatic chemiluminescent immunoassay (CLIA) for NT-IGFBP-4 was developed and its distribution across CVDs was evaluated in this study.
Methods
Fragment-specific monoclonal antibodies were used to develop immunoassay, followed by comprehensive analytical validation, including limit of blank (LoB), limit of detection (LoD), limit of quantification (LoQ), linearity, specificity, precision, sample type compatibility, and stability. Reference intervals for NT-IGFBP-4 were established in healthy individuals, with variations analyzed based on gender, age, body mass index (BMI), and renal function. Additionally, NT-IGFBP-4 distribution was explored in CVD patients.
Results
The newly developed chemiluminescence assay demonstrated high specificity for NT-IGFBP-4, with excellent sensitivity (LoQ=1.0 ng/mL), broad linearity (1.0–1,000.0 ng/mL), and strong precision (CV≤3.0 %). It showed no interference from common endogenous substances, maintained compatible with various sample types, and remained stable under different storage conditions. Reference intervals showed slight variations by gender and age, with levels being independent of BMI but influenced by renal function. NT-IGFBP-4 levels were significantly elevated in CVDs, especially in heart failure, correlating with NYHA classification and LVEF (%), with higher levels indicating worse cardiac function.
Conclusions
The new automatic NT-IGFBP-4 (CLIA) assay offers a highly specific, sensitive and precise method for quantifying IGFBP-4 fragments. Its validated performance and disease association findings would enhance its diagnostic and prognostic potential in CVD research, particularly in heart failure.
Funding source: Noncommunicable Chronic Diseases-National Science and Technology Major Project
Award Identifier / Grant number: 2023ZD0509500
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Research ethics: The present study carried out at Wuhan Asia Heart hospital (Wuhan, Hubei province, China) was approved by the Ethics Committee in accordance with the Helsinki Declaration.
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Informed consent: Not applicable.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Use of Large Language Models, AI and Machine Learning Tools: None declared.
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Conflict of interest: The authors state no conflict of interest.
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Research funding: This study was supported by Noncommunicable Chronic Diseases-National Science and Technology Major Project (2023ZD0509500) and Shenzhen Mindray Bio-Medical Electronics Co., Ltd.
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Data availability: The data that support the findings of this study are available from the corresponding authors, Z. Z. and Y. Z., upon reasonable request.
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Patents: Shenzhen Mindray Bio-Medical Electronics Co., Ltd. has filed for the patent application CN202411990243.4.
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Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/cclm-2025-0378).
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