Evidence map›Paper›PMID 29942300›Full record

ArticleFrontiers in immunology2018

Complement Component 3 Negatively Regulates Antibody Response by Modulation of Red Blood Cell Antigen.

Amanda Mener, Connie M Arthur, Seema R Patel, Jingchun Liu, Jeanne E Hendrickson, Sean R Stowell

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

33 citing papers in PubMed, 39 citations in OpenAlex.

  1. Acute Incompatible Red Blood Cell Transfusion in Mice.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  2. Article
  3. Analysis of Erythrocyte Membrane Alloantigens.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  4. The Immunology of Transfusion Medicine: Past, Present, and Future.Methods in molecular biology (Clifton, N.J.) · 2026
    Review
  5. Article
  6. Use of Microbial Microarrays to Define Antibody Specificity.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  7. Flow Cytometric Examination of Galectin Binding to Red Blood Cells.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  8. Article
  9. Research progress in RBC alloimmunization.Frontiers in immunology · 2025
    Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
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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

6 authors at 2 institutions in 1 country.

Amanda MenerCenter for Transfusion Medicine and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, United States.
Connie M ArthurCenter for Transfusion Medicine and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, United States.
Seema R PatelCenter for Transfusion Medicine and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, United States.
Jingchun LiuDepartment of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, United States.
Jeanne E HendricksonDepartment of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, United States.
Sean R StowellCenter for Transfusion Medicine and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, United States.
Emory University · USYale University · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM008169 · NIGMS · EMORY UNIVERSITY · PI GROSS, ROBERT E · 1987 to 2021
$20.3M
The Mouse Blood Center CoreP01HL132819 · NHLBI · UNIVERSITY OF VIRGINIA · PI ZIMRING, JAMES C. · 2017 to 2021
$12.2M
Engineering iPSC-RBCs for TransfusionR01HL138656 · NHLBI · EMORY UNIVERSITY · PI ROBACK, JOHN D, STOWELL, SEAN R · 2017 to 2020
$2.9M
Examination of Initiating Factors that Regulate Red Blood Cell AlloimmunizationR01HL135575 · NHLBI · EMORY UNIVERSITY · PI Sean R Stowell · 2017 to 2026
$2.8M
Examination of Innate Immunity Against Molecular MimicryDP5OD019892 · OD · EMORY UNIVERSITY · PI STOWELL, SEAN R · 2014 to 2018
$2.2M
Protecting Fetuses and Newborns from Maternal RBC AlloantibodiesR01HL126076 · NHLBI · YALE UNIVERSITY · PI HENDRICKSON, JEANNE E · 2014 to 2018
$2.1M
The role of complement component 3 in red blood cell alloimmunizationF31HL131428 · NHLBI · EMORY UNIVERSITY · PI MENER, AMANDA · 2016 to 2017
$98k
NHLBI NIH HHS F31 HL131428NHLBI NIH HHS P01 HL132819NHLBI NIH HHS R01 HL126076NHLBI NIH HHS R01 HL135575NHLBI NIH HHS R01 HL138656NIGMS NIH HHS T32 GM008169NIH HHS DP5 OD019892
6 · The paper itself

Abstract

Red blood cell (RBC) alloimmunization can make it difficult to procure compatible RBCs for future transfusion, directly leading to increased morbidity and mortality in transfusion-dependent patients. However, the factors that regulate RBC alloimmunization remain incompletely understood. As complement has been shown to serve as a key adjuvant in the development of antibody (Ab) responses against microbes, we examined the impact of complement on RBC alloimmunization. In contrast to the impact of complement component 3 (C3) in the development of an immune response following microbial exposure, transfusion of C3 knockout (C3 KO) recipients with RBCs expressing KEL (KEL RBCs) actually resulted in an enhanced anti-KEL Ab response. The impact of C3 appeared to be specific to KEL, as transfusion of RBCs bearing another model antigen, the chimeric HOD antigen (hen egg lysozyme, ovalbumin and Duffy), into C3 KO recipients failed to result in a similar increase in Ab formation. KEL RBCs experienced enhanced C3 deposition and loss of detectable target antigen over time when compared to HOD RBCs, suggesting that C3 may inhibit Ab formation by impacting the accessibility of the target KEL antigen. Loss of detectable KEL on the RBC surface did not reflect antigen masking by C3, but instead appeared to result from actual removal of the KEL antigen, as western blot analysis demonstrated complete loss of detectable KEL protein. Consistent with this, exposure of wild-type B6 or C3 KO recipients to KEL RBCs with reduced levels of detectable KEL antigen resulted in a significantly reduced anti-KEL Ab response. These results suggest that C3 possesses a unique ability to actually suppress Ab formation following transfusion by reducing the availability of the target antigen on the RBC surface.

Indexed as

Erythrocyte TransfusionAnimalsAntibody FormationAntigensComplement C3ErythrocytesFemaleMice, Inbred C57BLMice, KnockoutAntigensC3 protein, mouseComplement C3alloimmunizationantigen modulationcomplement component 3humoral immunityred blood cells

Identifiers

PMID29942300
PMCPMC6004516
OpenAlexW2808592588

What Socratic holds

Textmetadata
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 Socratic graph.