Donor genetics and storage conditions influence mitochondrial DNA and extracellular vesicle levels in RBC units.

IF 6.1 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

JCI insight Pub Date : 2025-06-10 eCollection Date: 2025-07-22 DOI:10.1172/jci.insight.187792

Xutao Deng, Clara Di Germanio, Erika G Marques de Menezes, Pamela Milani, Mars Stone, Heather Tanner, Sonia Coco Bakkour, Daniel M Chafets, Sarah E Reese, Nareg H Roubinian, Steven Kleinman, Tamir Kanias, Michael P Busch, Eric J Earley, Grier P Page, Travis Nemkov, Angelo D'Alessandro, Philip J Norris

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引用次数: 0

Abstract

Mitochondrial DNA (mtDNA) shares characteristics with bacterial DNA and activates immune cells via TLR9Extracellular vesicles (EVs) and mtDNA have been found in blood products and can activate immune cells; we sought to characterize their evolution in stored blood products. From a previous study of hemolysis in 13,403 blood donors, a second blood unit was drawn from 651 donors and sampled at days 10, 21, and 42. EV counts and RBC-EVs increased with storage time, and EV levels were higher in males and in RBC units processed in AS-1 compared with AS-3. mtDNA levels were higher in females and RBC units processed in AS-3. EV populations and mtDNA levels were highly correlated within donors for 98 donations obtained 2-12 months apart. Quantitative trait locus analysis revealed several genetic associations, most notably linking mtDNA levels with polymorphisms in ANKLE1, which encodes an erythroid-specific protein that preferentially cleaves mtDNA. These data suggest that donor-intrinsic factors may influence mtDNA and EV levels found in RBC units. This finding lends impetus to determining if genetic or environmental factors control levels of these immune mediators in blood donors.

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供体遗传和储存条件影响红细胞单位的线粒体DNA和细胞外囊泡水平。

线粒体DNA （mtDNA）与细菌DNA具有相同的特征，并通过Toll样受体(TLR)-9激活免疫细胞。在血液制品中发现了细胞外囊泡（EVs）和mtDNA，它们可以激活免疫细胞；我们试图描述它们在储存血液制品中的进化特征。在之前对13403名献血者溶血的研究中，从651名献血者中抽取第二个血液单位，并在第10、21和42天取样。EV计数和红细胞-EV随着储存时间的增加而增加，与AS-3相比，男性和AS-1处理的RBC单位的EV水平更高。mtDNA水平在女性和AS-3处理的RBC单位中较高。在相隔2-12个月的98例献血者中，EV种群与mtDNA水平高度相关。数量性状位点分析揭示了一些遗传关联，最值得注意的是mtDNA水平与ANKLE1多态性的联系，ANKLE1编码一种红细胞特异性蛋白，优先切割mtDNA。这些数据表明，供体内在因素可能影响红细胞单位中mtDNA和EV水平。这一发现有助于确定是遗传因素还是环境因素控制了献血者体内这些免疫介质的水平。

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

JCI insight Medicine-General Medicine

CiteScore

13.70

自引率

1.20%

发文量

543

审稿时长

6 weeks

期刊介绍： JCI Insight is a Gold Open Access journal with a 2022 Impact Factor of 8.0. It publishes high-quality studies in various biomedical specialties, such as autoimmunity, gastroenterology, immunology, metabolism, nephrology, neuroscience, oncology, pulmonology, and vascular biology. The journal focuses on clinically relevant basic and translational research that contributes to the understanding of disease biology and treatment. JCI Insight is self-published by the American Society for Clinical Investigation (ASCI), a nonprofit honor organization of physician-scientists founded in 1908, and it helps fulfill the ASCI's mission to advance medical science through the publication of clinically relevant research reports.