An automatic chemiluminescence immunoassay for a novel biomarker NT-IGFBP-4: analytical performance and clinical relevance in heart failure.

IF 3.7 2区医学 Q1 MEDICAL LABORATORY TECHNOLOGY

Clinical chemistry and laboratory medicine Pub Date : 2025-08-25 DOI:10.1515/cclm-2025-0378

Shuzheng Cao, Jing Wang, Ling Li, Yu Wu, Juan Yang, Litao Zhang, Xin Shu, Hui Wang, Yisha Jing, Yi Zhang, Zhenlu Zhang

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引用次数: 0

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.

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新型生物标志物NT-IGFBP-4的自动化学发光免疫分析：在心力衰竭中的分析性能和临床相关性

目的：胰岛素样生长因子结合蛋白-4 （IGFBP-4）片段被报道为心血管疾病（CVD）风险评估的新兴生物标志物。为了确保数据的可靠性和提高临床应用，本研究首次开发了NT-IGFBP-4的自动化学发光免疫分析法（CLIA），并评估了其在心血管疾病中的分布。方法：采用片段特异性单克隆抗体建立免疫分析法，并进行空白限（LoB）、检出限（LoD）、定量限（LoQ）、线性度、特异性、精密度、样品类型相容性、稳定性等综合分析验证。在健康个体中建立NT-IGFBP-4的参考区间，并根据性别、年龄、体重指数（BMI）和肾功能分析差异。此外，研究NT-IGFBP-4在CVD患者中的分布。结果：新建立的化学发光法对NT-IGFBP-4具有高特异性，灵敏度高（LoQ=1.0 ng/mL），线性宽（1.0 ~ 10000.0 ng/mL），精密度高（CV≤3.0 %）。它不受常见内源物质的干扰，与各种样品类型保持相容，在不同的储存条件下保持稳定。参考区间因性别和年龄而略有差异，其水平与BMI无关，但受肾功能影响。NT-IGFBP-4水平在心血管疾病中显著升高，特别是在心力衰竭中，与NYHA分类和LVEF（%）相关，水平越高表明心功能越差。结论：新建立的NT-IGFBP-4 （CLIA）自动检测方法为IGFBP-4片段的定量提供了一种高特异性、高灵敏度和高精确度的方法。其验证的性能和疾病关联发现将增强其在心血管疾病研究中的诊断和预后潜力，特别是在心力衰竭方面。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical chemistry and laboratory medicine 医学-医学实验技术

CiteScore

11.30

自引率

16.20%

发文量

306

审稿时长

3 months

期刊介绍： Clinical Chemistry and Laboratory Medicine (CCLM) publishes articles on novel teaching and training methods applicable to laboratory medicine. CCLM welcomes contributions on the progress in fundamental and applied research and cutting-edge clinical laboratory medicine. It is one of the leading journals in the field, with an impact factor over 3. CCLM is issued monthly, and it is published in print and electronically. CCLM is the official journal of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) and publishes regularly EFLM recommendations and news. CCLM is the official journal of the National Societies from Austria (ÖGLMKC); Belgium (RBSLM); Germany (DGKL); Hungary (MLDT); Ireland (ACBI); Italy (SIBioC); Portugal (SPML); and Slovenia (SZKK); and it is affiliated to AACB (Australia) and SFBC (France). Topics: - clinical biochemistry - clinical genomics and molecular biology - clinical haematology and coagulation - clinical immunology and autoimmunity - clinical microbiology - drug monitoring and analysis - evaluation of diagnostic biomarkers - disease-oriented topics (cardiovascular disease, cancer diagnostics, diabetes) - new reagents, instrumentation and technologies - new methodologies - reference materials and methods - reference values and decision limits - quality and safety in laboratory medicine - translational laboratory medicine - clinical metrology Follow @cclm_degruyter on Twitter!