Evidence map›Paper›PMID 31899794›Full record

ArticleBlood2020

Antibodies against the erythroferrone N-terminal domain prevent hepcidin suppression and ameliorate murine thalassemia.

João Arezes, Niall Foy, Kirsty McHugh, Doris Quinkert, Susan Benard, Anagha Sawant, Joe N Frost, Andrew E Armitage, Sant-Rayn Pasricha, Pei Jin Lim and 9 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
6.2field-weighted citation impact, top 3% 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

44 citing papers in PubMed, 67 citations in OpenAlex.

  1. Trial
  2. Thalassaemia.Nature reviews. Disease primers · 2026
    Review
  3. Molecular and therapeutic frontiers in anemia therapy.The Journal of clinical investigation · 2026
    Review
  4. Article
  5. Review
  6. Noggin alleviates neuropathic pain by regulating microglial polarization and remodeling iron homeostasis via a STAT3-dependent pathway.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025
    Article
  7. Review
  8. Review
  9. Metal Ion Signaling in Biomedicine.Chemical reviews · 2025
    Review
  10. Outline of Iron Metabolism, with Emphasis on Erythroid Cells.Mediterranean journal of hematology and infectious diseases · 2025
    Review
  11. Review
  12. Article
  13. Current Landscape of Hepcidin Therapeutics.Advances in experimental medicine and biology · 2025
    Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 5 institutions in 4 countries.

João ArezesMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Niall FoyBioMedicine Design, Pfizer Biotherapeutics R&D, Dublin, Ireland.
Kirsty McHughJenner Institute, University of Oxford, Oxford, United Kingdom.
Doris QuinkertJenner Institute, University of Oxford, Oxford, United Kingdom.
Susan BenardBioMedicine Design, Pfizer Biotherapeutics R&D, Cambridge, MA.
Anagha SawantRare Disease Research Unit, Pfizer Inc., Cambridge, MA.
Joe N FrostMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Andrew E ArmitageMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Sant-Rayn PasrichaMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Pei Jin LimMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
May S TamRare Disease Research Unit, Pfizer Inc., Cambridge, MA.
Edward LavallieRare Disease Research Unit, Pfizer Inc., Cambridge, MA.
Debra D PittmanRare Disease Research Unit, Pfizer Inc., Cambridge, MA.
Orla CunninghamBioMedicine Design, Pfizer Biotherapeutics R&D, Dublin, Ireland.
Matthew LambertBioMedicine Design, Pfizer Biotherapeutics R&D, Dublin, Ireland.
John E MurphyRare Disease Research Unit, Pfizer Inc., Cambridge, MA.
Simon J DraperJenner Institute, University of Oxford, Oxford, United Kingdom.
Reema JasujaRare Disease Research Unit, Pfizer Inc., Cambridge, MA.
Hal DrakesmithMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Pfizer (United States) · USJohn Radcliffe Hospital · GBPfizer (Ireland) · IEUniversity of Oxford · GBThe University of Melbourne · AU

Funding

Medical Research Council G0901149Medical Research Council MC_UU_00008/10Medical Research Council MC_UU_12010/10Wellcome TrustWellcome Trust 106917/Z/15/Z
6 · The paper itself

Abstract

Erythroferrone (ERFE) is produced by erythroblasts in response to erythropoietin (EPO) and acts in the liver to prevent hepcidin stimulation by BMP6. Hepcidin suppression allows for the mobilization of iron to the bone marrow for the production of red blood cells. Aberrantly high circulating ERFE in conditions of stress erythropoiesis, such as in patients with β-thalassemia, promotes the tissue iron accumulation that substantially contributes to morbidity in these patients. Here we developed antibodies against ERFE to prevent hepcidin suppression and to correct the iron loading phenotype in a mouse model of β-thalassemia [Hbb(th3/+) mice] and used these antibodies as tools to further characterize ERFE's mechanism of action. We show that ERFE binds to BMP6 with nanomolar affinity and binds BMP2 and BMP4 with somewhat weaker affinities. We found that BMP6 binds the N-terminal domain of ERFE, and a polypeptide derived from the N terminus of ERFE was sufficient to cause hepcidin suppression in Huh7 hepatoma cells and in wild-type mice. Anti-ERFE antibodies targeting the N-terminal domain prevented hepcidin suppression in ERFE-treated Huh7 cells and in EPO-treated mice. Finally, we observed a decrease in splenomegaly and serum and liver iron in anti-ERFE-treated Hbb(th3/+) mice, accompanied by an increase in red blood cells and hemoglobin and a decrease in reticulocyte counts. In summary, we show that ERFE binds BMP6 directly and with high affinity, and that antibodies targeting the N-terminal domain of ERFE that prevent ERFE-BMP6 interactions constitute a potential therapeutic tool for iron loading anemias.

Indexed as

AnimalsAntibodies, NeutralizingCell LineCytokinesHEK293 CellsHepcidinsHumansIronMaleMice, Inbred C57BLMuscle ProteinsProtein DomainsThalassemiaAntibodies, NeutralizingCytokinesErfe protein, mouseHepcidinsIronMuscle Proteins

Identifiers

PMID31899794
PMCPMC7046598
OpenAlexW2990952455

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.