Evidence map›Paper›PMID 40493412›Full record

ArticleJCI insight2025

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

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 and 9 more

Abstract read
In one paragraph

Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Altered Erythrocyte Function via TLR9-ox-mtDNA Binding Links Mitochondrial Oxidative Damage to Systemic Inflammation in Multiple Sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Xutao DengVitalant Research Institute, San Francisco, California, USA.
Clara Di GermanioVitalant Research Institute, San Francisco, California, USA.
Erika G Marques de MenezesVitalant Research Institute, San Francisco, California, USA.
Pamela MilaniVitalant Research Institute, San Francisco, California, USA.
Mars StoneVitalant Research Institute, San Francisco, California, USA.
Heather TannerVitalant Research Institute, San Francisco, California, USA.
Sonia Coco BakkourVitalant Research Institute, San Francisco, California, USA.
Daniel M ChafetsVitalant Research Institute, San Francisco, California, USA.
Sarah E ReeseWestat, Rockville, Maryland, USA.
Nareg H RoubinianVitalant Research Institute, San Francisco, California, USA.
Steven KleinmanUniversity of British Columbia, Victoria, British Columbia, Canada.
Tamir KaniasVitalant Research Institute, San Francisco, California, USA.
Michael P BuschVitalant Research Institute, San Francisco, California, USA.
Eric J EarleyResearch Triangle Institute International, Atlanta, Georgia, USA.
Grier P PageResearch Triangle Institute International, Atlanta, Georgia, USA.
Travis NemkovUniversity of Colorado, Denver-Anschutz Medical Campus, Aurora, Colorado, USA.
Angelo D'AlessandroUniversity of Colorado, Denver-Anschutz Medical Campus, Aurora, Colorado, USA.
Philip J NorrisVitalant Research Institute, San Francisco, California, USA.
Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P)

Funding

(REDS-IV-P) RECIPIENT EPIDEMIOLOGY AND DONOR EVALUATION STUDY IV-DATA75N92019D00032 · NHLBI · WESTAT, INC. · PI CHAPMAN, KATHY · 2019 to 2025
$19.6M
REDS-IV-P - CENTER FOR TRANSFUSION LABORATORY STUDIES (CTLS) - SARS-CoV-2/COVID-19 STUDIES75N92019D00033 · NHLBI · VITALANT · PI NORRIS, PHILIP J. · 2019 to 2024
$15.6M
The Impact of Oxidative Stress on Erythocyte BiologyR01HL148151 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI D'ALESSANDRO, ANGELO, KARAFIN, MATTHEW S · 2019 to 2022
$8.9M
The role of ferroptosis in red cell aging in vivo and in vitroR01HL146442 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI Angelo D'Alessandro, Adam N. Goldfarb · 2019 to 2026
$5.4M
NHLBI NIH HHS 75N92019D00032NHLBI NIH HHS 75N92019D00033NHLBI NIH HHS R01 HL146442NHLBI NIH HHS R01 HL148151
6 · The paper itself

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.

Indexed as

Blood DonorsBlood PreservationDNA, MitochondrialErythrocytesExtracellular VesiclesAdultFemaleHumansMaleMiddle AgedQuantitative Trait LociDNA, MitochondrialCell biologyHematologyInnate immunity

Identifiers

PMID40493412
PMCPMC12288979

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.