干血斑mRNA生物标志物可提高个体化方法对自体血液微量输血的检测。

IF 2.7 3区 医学 Q2 BIOCHEMICAL RESEARCH METHODS
Andreas Breenfeldt Andersen, Jessica Almeida Oliveira, Francesco Loria, Jacob Bejder, Olivier Salamin, Tiia Kuuranne, Nikolai B Nordsborg, Nicolas Leuenberger
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引用次数: 0

摘要

世界反兴奋剂机构(WADA)禁止自体输血(ABTs),但检测自体微量输血(abmt)仍然是一个挑战。由于输血量较小,abmt导致生物标志物变化减弱,限制了运动员生物护照(ABP)的检测灵敏度。本研究评估了5-氨基乙酰丙酸合成酶(ALAS2)和碳酸酐酶1 (CA1)的mRNA表达,从干血斑(DBS)中测量,是否可以作为ABMT的敏感生物标志物。在一项随机、安慰剂对照设计中,47名训练有素的个体(24♀;平均VO2peak(56±7 mL·min-1·kg-1)分为ABMT组(n = 23;♀= 12)或安慰剂组(n = 24;♀= 12)。ABMT组献血450 mL, 4周后接受130 mL填充红细胞回输。献血和回输前后均定期采血。分析DBS组织中ALAS2和CA1 mRNA的表达及静脉血网织红细胞百分比(RET%)。献血后,ALAS2、CA1和RET%分别增加270%、200%和150%。然而,在ABMT后没有观察到一致的组水平变化。与CA1相比,个体化分析发现ALAS2的异常值更多,对个体mRNA谱的盲法解释在检测ABMT方面的灵敏度和特异性达到了95%。这些发现表明,通过微创DBS取样评估ALAS2 mRNA表达,是一种很有前途的识别ABMT的生物标志物。这种方法可以通过提高对逃避传统ABP生物标志物检测的小体积自体输血的敏感性来增强当前的反兴奋剂策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
mRNA Biomarkers in Dried Blood Spots May Improve Detection of Autologous Blood Micro-Transfusions Using an Individualized Approach.

Autologous blood transfusions (ABTs) are prohibited by the World Anti-Doping Agency (WADA), yet detecting autologous blood micro-transfusions (ABMTs) remains a challenge. Due to smaller transfused volumes, ABMTs cause attenuated biomarker changes, limiting detection sensitivity within the Athlete Biological Passport (ABP). This study assessed whether mRNA expression of 5-aminolevulinic acid synthase (ALAS2) and carbonic anhydrase 1 (CA1), measured from dried blood spots (DBS), could serve as sensitive biomarkers of ABMT. In a randomized, placebo-controlled design, 47 trained individuals (24 ♀; mean VO2peak 56 ± 7 mL·min-1·kg-1) were allocated to an ABMT group (n = 23; ♀ = 12) or placebo group (n = 24; ♀ = 12). The ABMT group donated 450 mL of blood and received a 130 mL packed red blood cell reinfusion 4 weeks later. Blood sampling occurred regularly before and after both donation and reinfusion. ALAS2 and CA1 mRNA expression from DBS, and reticulocyte percentage (RET%) from venous blood, were analyzed. Following blood donation, ALAS2, CA1, and RET% increased by 270%, 200%, and 150%, respectively. However, no consistent group-level changes were observed after ABMT. Individualized analysis identified more outliers for ALAS2 than for CA1, and blinded interpretation of individual mRNA profiles achieved > 95% sensitivity and specificity for detecting ABMT. These findings suggest that ALAS2 mRNA expression, assessed via minimally invasive DBS sampling, is a promising biomarker for identifying ABMT. This approach may enhance current anti-doping strategies by improving sensitivity to small-volume autologous transfusions that evade detection through traditional ABP biomarkers.

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来源期刊
Drug Testing and Analysis
Drug Testing and Analysis BIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL
CiteScore
5.90
自引率
24.10%
发文量
191
审稿时长
2.3 months
期刊介绍: As the incidence of drugs escalates in 21st century living, their detection and analysis have become increasingly important. Sport, the workplace, crime investigation, homeland security, the pharmaceutical industry and the environment are just some of the high profile arenas in which analytical testing has provided an important investigative tool for uncovering the presence of extraneous substances. In addition to the usual publishing fare of primary research articles, case reports and letters, Drug Testing and Analysis offers a unique combination of; ‘How to’ material such as ‘Tutorials’ and ‘Reviews’, Speculative pieces (‘Commentaries’ and ‘Perspectives'', providing a broader scientific and social context to the aspects of analytical testing), ‘Annual banned substance reviews’ (delivering a critical evaluation of the methods used in the characterization of established and newly outlawed compounds). Rather than focus on the application of a single technique, Drug Testing and Analysis employs a unique multidisciplinary approach to the field of controversial compound determination. Papers discussing chromatography, mass spectrometry, immunological approaches, 1D/2D gel electrophoresis, to name just a few select methods, are welcomed where their application is related to any of the six key topics listed below.
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