Evidence map›Paper›PMID 34019619›Full record

ArticleBlood2022

Nonhuman glycans can regulate anti-factor VIII antibody formation in mice.

Connie M Arthur, Patricia E Zerra, Sooncheon Shin, Jianmei Wang, Xeuzheng Song, Christopher B Doering, Pete Lollar, Shannon Meeks, Sean R Stowell

Open access · greenAbstract read
In one paragraph

Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

30 citing papers in PubMed, 24 citations in OpenAlex.

  1. The Immunology of Transfusion Medicine: Past, Present, and Future.Methods in molecular biology (Clifton, N.J.) · 2026
    Review
  2. Mouse Model of Hemolytic Disease of the Fetus and Newborn.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  3. Analysis of Erythrocyte Membrane Alloantigens.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  4. Acute Incompatible Red Blood Cell Transfusion in Mice.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  5. Anemia and Transfusion in Preclinical Models of Neonatology.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  6. Use of Microbial Microarrays to Define Antibody Specificity.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  7. Expression and Characterization of Blood Group Binding Lectins.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  8. Analysis of Galectin Binding to Blood Group Expressing Bacteria.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  9. Article
  10. Murine Models of Transfusion-Induced Red Blood Cell Alloimmunization.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  11. Analysis of Biotinylated Red Blood Cells Following Transfusion.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  12. Article
  13. Exploration of biomarkers for inhibitor development in persons with hemophilia A.Research and practice in thrombosis and haemostasis · 2025
    Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. The role of glycosylation in clinical allergy and immunology.The Journal of allergy and clinical immunology · 2024
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Connie M ArthurCenter for Transfusion Medicine and Cellular Therapies, Department of Laboratory Medicine and Pathology.
Patricia E ZerraCenter for Transfusion Medicine and Cellular Therapies, Department of Laboratory Medicine and Pathology.ORCID 0000-0003-3675-2725
Sooncheon ShinCenter for Transfusion Medicine and Cellular Therapies, Department of Laboratory Medicine and Pathology.
Jianmei WangCenter for Transfusion Medicine and Cellular Therapies, Department of Laboratory Medicine and Pathology.
Xeuzheng SongDepartment of Biochemistry.
Christopher B DoeringDepartment of Pediatrics, Emory University School of Medicine, Atlanta, GA; and.ORCID 0000-0002-5662-0060
Pete LollarDepartment of Pediatrics, Emory University School of Medicine, Atlanta, GA; and.ORCID 0000-0002-1206-8104
Shannon MeeksDepartment of Pediatrics, Emory University School of Medicine, Atlanta, GA; and.ORCID 0000-0002-3683-8644
Sean R StowellCenter for Transfusion Medicine and Cellular Therapies, Department of Laboratory Medicine and Pathology.
Institute for Transfusion Medicine · USEmory University · USBrigham and Women's Hospital · US

Funding

Unraveling the immune response to factor VIIIU54HL141981 · NHLBI · EMORY UNIVERSITY · PI MEEKS, SHANNON L. · 2018 to 2022
$8.1M
Atlanta Pediatric Scholars ProgramK12HD072245 · NICHD · EMORY UNIVERSITY · PI Shari Barkin · 2012 to 2026
$5.5M
Examination of Initiating Factors that Regulate Red Blood Cell AlloimmunizationR01HL135575 · NHLBI · EMORY UNIVERSITY · PI Sean R Stowell · 2017 to 2026
$2.8M
Defining Initiating Factors Responsible for the Development of FVIII InhibitorsR01HL141335 · NHLBI · EMORY UNIVERSITY · PI MEEKS, SHANNON L. · 2018 to 2022
$2.3M
Examination of Innate Immunity Against Molecular MimicryDP5OD019892 · OD · EMORY UNIVERSITY · PI STOWELL, SEAN R · 2014 to 2018
$2.2M
Examining the Mechanisms of RBC Alloimmunization HyperrespondersR01HL154034 · NHLBI · EMORY UNIVERSITY · PI ARTHUR, CONNIE M · 2020 to 2024
$2.1M
NHLBI NIH HHS R01 HL135575NHLBI NIH HHS R01 HL141335NHLBI NIH HHS R01 HL154034NHLBI NIH HHS U54 HL141981NICHD NIH HHS K12 HD072245NIH HHS DP5 OD019892
6 · The paper itself

Abstract

Recombinant factor VIII (FVIII) products represent a life-saving intervention for patients with hemophilia A. However, patients can develop antibodies against FVIII that prevent its function and directly increase morbidity and mortality. The development of anti-FVIII antibodies varies depending on the type of recombinant product used, with previous studies suggesting that second-generation baby hamster kidney (BHK)-derived FVIII products display greater immunogenicity than do third-generation Chinese hamster ovary (CHO)-derived FVIII products. However, the underlying mechanisms responsible for these differences remain incompletely understood. Our results demonstrate that BHK cells express higher levels of the nonhuman carbohydrate α1-3 galactose (αGal) than do CHO cells, suggesting that αGal incorporation onto FVIII may result in anti-αGal antibody recognition that could positively influence the development of anti-FVIII antibodies. Consistent with this, BHK-derived FVIII exhibits increased levels of αGal, which corresponds to increased reactivity with anti-αGal antibodies. Infusion of BHK-derived, but not CHO-derived, FVIII into αGal-knockout mice, which spontaneously generate anti-αGal antibodies, results in significantly higher anti-FVIII antibody formation, suggesting that the increased levels of αGal on BHK-derived FVIII can influence immunogenicity. These results suggest that posttranslational modifications of recombinant FVIII products with nonhuman carbohydrates may influence the development of anti-FVIII antibodies.

Indexed as

AntibodiesAntibody FormationBlood Coagulation Factor InhibitorsFactor VIIIPolysaccharidesAnimalsCHO CellsCricetinaeCricetulusHemophilia AMiceMice, KnockoutProtein Processing, Post-TranslationalRecombinant ProteinsAntibodiesBlood Coagulation Factor InhibitorsF8 protein, humanFactor VIIIPolysaccharidesRecombinant Proteins

Identifiers

PMID34019619
PMCPMC8900271
OpenAlexW3161761722

What OpenQuestion holds

Textmetadata
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.