Evidence map›Paper›PMID 36907655›Full record

ArticleTransfusion2023

Class switching is differentially regulated in RBC alloimmunization and vaccination.

Anupam Prakash, Jelena Medved, Abhinav Arneja, Conrad Niebuhr, Andria N Li, Soraya Tarrah, Alexis R Boscia, Emily D Burnett, Aanika Singh, Juan E Salazar and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Transfusion, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.5field-weighted citation impact, top 28% of its field
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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Anupam PrakashDepartment of Pathology, University of Virginia, Charlottesville, Virginia, USA.
Jelena MedvedDepartment of Pathology, University of Virginia, Charlottesville, Virginia, USA.ORCID 0000-0001-8467-2098
Abhinav ArnejaDepartment of Pathology, University of Virginia, Charlottesville, Virginia, USA.
Conrad NiebuhrDepartment of Pathology, University of Virginia, Charlottesville, Virginia, USA.
Andria N LiDepartment of Pathology, University of Virginia, Charlottesville, Virginia, USA.
Soraya TarrahDepartment of Pathology, University of Virginia, Charlottesville, Virginia, USA.
Alexis R BosciaDepartment of Pathology, University of Virginia, Charlottesville, Virginia, USA.
Emily D BurnettDepartment of Pathology, University of Virginia, Charlottesville, Virginia, USA.
Aanika SinghDepartment of Pathology, University of Virginia, Charlottesville, Virginia, USA.
Juan E SalazarDepartment of Pathology, University of Virginia, Charlottesville, Virginia, USA.
Wenhao XuDepartment of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia, USA.
Manjula SanthanakrishnanDepartment of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Jeanne E HendricksonDepartment of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.ORCID 0000-0002-7928-3132
Chance John LuckeyDepartment of Pathology, University of Virginia, Charlottesville, Virginia, USA.ORCID 0000-0002-0787-9121
University of Virginia · USEmory University · USYale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Women's Oncology Program - WONP30CA044579 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Dina Gould Halme · 1987 to 2026
$72.1M
The Mouse Blood Center CoreP01HL132819 · NHLBI · UNIVERSITY OF VIRGINIA · PI LUCKEY, CHANCE MARION JOHN · 2017 to 2021
$12.2M
INTERDISCIPLINARY TRAINING PROGRAM IN IMMUNOLOGYT32AI007496 · NIAID · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Michael G. Brown, Coleen A McNamara · 1995 to 2026
$10.2M
Cyokine control of red blood cell alloimmunizationR01HL134691 · NHLBI · UNIVERSITY OF VIRGINIA · PI LUCKEY, CHANCE MARION JOHN · 2017 to 2020
$2.1M
Cytokine control of Red Blood Cell AlloimmunizationR21HL111866 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LUCKEY, CHANCE MARION JOHN · 2012 to 2013
$463k
NCATS NIH HHS UL1 TR001863NCI NIH HHS P30 CA044579NHLBI NIH HHS P01 HL132819NHLBI NIH HHS R01 HL134691NHLBI NIH HHS R21 HL111866NIAID NIH HHS T32 AI007496
6 · The paper itself

Abstract

backgroundStudies of human patients have shown that most anti-RBC alloantibodies are IgG1 or IgG3 subclasses, although it is unclear why transfused RBCs preferentially drive these subclasses over others. Though mouse models allow for the mechanistic exploration of class-switching, previous studies of RBC alloimmunization in mice have focused more on the total IgG response than the relative distribution, abundance, or mechanism of IgG subclass generation. Given this major gap, we compared the IgG subclass distribution generated in response to transfused RBCs relative to protein in alum vaccination, and determined the role of STAT6 in their generation. STUDY DESIGN AND

methodsWT mice were either immunized with Alum/HEL-OVA or transfused with HOD RBCs and levels of anti-HEL IgG subtypes were measured using end-point dilution ELISAs. To study the role of STAT6 in IgG class-switching, we first generated and validated novel STAT6 KO mice using CRISPR/cas9 gene editing. STAT6 KO mice were then transfused with HOD RBCs or immunized with Alum/HEL-OVA, and IgG subclasses were quantified by ELISA.

resultsWhen compared with antibody responses to Alum/HEL-OVA, transfusion of HOD RBCs induced lower levels of IgG1, IgG2b, and IgG2c but similar levels of IgG3. Class switching to most IgG subtypes remained largely unaffected in STAT6 deficient mice in response to HOD RBC transfusion, with the one exception being IgG2b. In contrast, STAT6 deficient mice showed altered levels of all IgG subtypes following Alum vaccination. DISCUSSION: Our results show that anti-RBC class-switching occurs via alternate mechanisms when compared with the well-studied immunogen alum vaccination.

Indexed as

ErythrocytesImmunoglobulin Class SwitchingAlum CompoundsAnimalsHumansImmunoglobulin GIsoantibodiesMiceVaccinationAlum Compoundsaluminum sulfateImmunoglobulin GIsoantibodiesclass switchingred blood cell alloimmunizationSTAT6vaccination

Identifiers

PMID36907655
PMCPMC10851675
OpenAlexW4323974918

What Socratic holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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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 Socratic graph.