全自动化学发光酶免疫分析法对乙型肝炎核心相关抗原成分、磷酸化和非磷酸化乙型肝炎核心抗原的评价:乙型肝炎e抗原血清转化过程中的临床意义和动态

IF 5.4 2区 医学 Q1 MICROBIOLOGY
Journal of Clinical Microbiology Pub Date : 2025-09-10 Epub Date: 2025-08-19 DOI:10.1128/jcm.00385-25
Takanori Suzuki, Chiharu Ohue, Osamu Arai, Yuka Inose, Katsuya Nagaoka, Shintaro Ogawa, Takako Inoue, Kentaro Matsuura, Katsumi Aoyagi, Shintaro Yagi, Yasuhito Tanaka
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引用次数: 0

摘要

为了评估乙型肝炎核心相关抗原(HBcrAg)、乙型肝炎核心抗原(HBcAg)和磷酸化HBcAg (pHBcAg)三种检测方法的性能和临床相关性,在定量HBcAg(乙型肝炎病毒(HBV)感染的关键生物标志物)时,开发了两种HBcAg变体的全自动化学发光酶免疫测定(CLEIA)。HBcAg和pHBcAg检测的截止值分别为2.50和2.10 LogU/mL。通过购买的100份血浆样品,各成分之间存在较强的相关性(r = 0.896 ~ 0.970)。当使用一系列乙型肝炎e抗原(HBeAg)血清转换面板分析HBcrAg组分的动态,以及与HBV标志物的相关性时,观察到不同的动态和分子谱。为了评估这些检测的临床相关性,从102名接受核苷类似物(NA)治疗的hbv感染患者中获得血清样本。在NA治疗期间,HBcAg和pHBcAg水平均显著降低,但模式不同,表明HBV活性独立于HBV DNA和源自pc-mRNA的持久性HBcrAg成分。OptiPrep密度梯度超离心分析鉴定pHBcAg为高密度馏分的主要成分。免疫沉淀和Western blotting证实HBcAg成分主要被乙型肝炎表面抗原(HBsAg)包裹,pHBcAg被鉴定为空病毒颗粒的主要成分。尽管本研究样本量有限,但在血清转化和治疗过程中HBcAg、pHBcAg和HBcrAg的不同动态表明,这些检测可以作为监测肝内HBV活性和治疗效果的独立生物标志物。本研究评估了用于乙型肝炎核心抗原(HBcAg)和磷酸化HBcAg (pHBcAg)的新型全自动化学发光酶免疫测定(CLEIA)系统,并确定pHBcAg是乙型肝炎病毒(HBV)衍生的空病毒颗粒的主要成分,挑战了先前的假设并为HBV生物标志物提供了新的见解。HBcAg和pHBcAg在乙型肝炎e血清转化和核苷治疗方面表现出与其他生物标志物(包括乙型肝炎核心相关抗原(HBcrAg)、HBV RNA和HBV DNA)不同的动态。开发的用于HBcAg和pHBcAg的CLEIA系统有望成为监测肝内HBV活性、免疫清除和非感染性病毒复制的工具。将这些生物标志物纳入临床实践可以完善HBV管理策略,改善再激活风险预测,并推进精准医学方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Evaluation of fully automated chemiluminescent enzyme immunoassays for hepatitis B core-related antigen components, phosphorylated and non-phosphorylated hepatitis B core antigens: clinical significance and dynamics during hepatitis B e antigen seroconversion.

Evaluation of fully automated chemiluminescent enzyme immunoassays for hepatitis B core-related antigen components, phosphorylated and non-phosphorylated hepatitis B core antigens: clinical significance and dynamics during hepatitis B e antigen seroconversion.

Evaluation of fully automated chemiluminescent enzyme immunoassays for hepatitis B core-related antigen components, phosphorylated and non-phosphorylated hepatitis B core antigens: clinical significance and dynamics during hepatitis B e antigen seroconversion.

Evaluation of fully automated chemiluminescent enzyme immunoassays for hepatitis B core-related antigen components, phosphorylated and non-phosphorylated hepatitis B core antigens: clinical significance and dynamics during hepatitis B e antigen seroconversion.

To assess the performance and clinical relevance of three assays-hepatitis B core-related antigen (HBcrAg), hepatitis B core antigen (HBcAg), and phosphorylated HBcAg (pHBcAg)-in quantifying HBcrAg, a critical biomarker of hepatitis B virus (HBV) infection, fully automated chemiluminescent enzyme immunoassays (CLEIA) for two HBcAg variants were developed. Cutoff values for HBcAg and pHBcAg assays were established at 2.50 and 2.10 LogU/mL, respectively. The strong correlations among components (r = 0.896-0.970) were observed by using purchased 100 plasma samples. When the dynamics of HBcrAg components were analyzed by using a series of hepatitis B e antigen (HBeAg) seroconversion panel, alongside correlations with HBV markers, distinct dynamics and molecular profiles were observed. For the assessment of the clinical relevance of these assays, serum samples were obtained from 102 HBV-infected patients treated with nucleos(t)ide analog (NA). Both HBcAg and pHBcAg levels were significantly reduced during NA therapy, but in different patterns, suggesting HBV activity independent of HBV DNA and persistent HBcrAg components derived from pc-mRNA. OptiPrep density gradient ultracentrifugation analysis identified pHBcAg as the dominant component in high-density fractions. Immunoprecipitation and Western blotting confirmed that HBcAg components were predominantly enveloped by hepatitis B surface antigen (HBsAg), with pHBcAg identified as the major component of empty viral particles. Although the limitation in sample size in this study, the revealed distinct dynamics of HBcAg, pHBcAg, and HBcrAg during seroconversion and treatment suggest these assays could serve as independent biomarkers for monitoring intrahepatic HBV activity and treatment efficacy.IMPORTANCEThis study evaluates novel fully automated chemiluminescent enzyme immunoassay (CLEIA) systems for hepatitis B core antigen (HBcAg) and phosphorylated HBcAg (pHBcAg) and identifies pHBcAg as the predominant component of hepatitis B virus (HBV)-derived empty viral particles, challenging previous assumptions and providing new insights into HBV biomarkers. HBcAg and pHBcAg show distinct dynamics in hepatitis B e seroconversion and nucleos(t)ide treatment from the other biomarkers including hepatitis B core-related antigen (HBcrAg), HBV RNA, and HBV DNA. The developed CLEIA systems for HBcAg and pHBcAg show promise as tools for monitoring intrahepatic HBV activity, immune clearance, and noninfectious viral replication. Incorporating these biomarkers into clinical practice could refine HBV management strategies, improve reactivation risk prediction, and advance precision medicine approaches.

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来源期刊
Journal of Clinical Microbiology
Journal of Clinical Microbiology 医学-微生物学
CiteScore
17.10
自引率
4.30%
发文量
347
审稿时长
3 months
期刊介绍: The Journal of Clinical Microbiology® disseminates the latest research concerning the laboratory diagnosis of human and animal infections, along with the laboratory's role in epidemiology and the management of infectious diseases.
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