Regulation of iron homeostasis through the erythroferrone-hepcidin axis in sickle cell disease

Abhishek A. Mangaonkar, Fahim Thawer, James Son, Germame H Ajebo, Hongyan Xu, Nadine J. Barrett, Leigh G. Wells, Latanya Bowman, Betsy Clair, Niren Patel, Pritam Bora, Grace Jung, Elizabeta Nemeth, Abdullah Kutlar

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Sickle cell disease (SCD) has a distinct pattern of transfusional iron overload (IO) when compared to transfusion-dependent β-thalassaemia major (TDT). We conducted a single institution prospective study to evaluate plasma biomarkers of iron regulation and inflammation in patients with SCD with IO (SCD IO cases, n = 22) and without IO (SCD non-IO cases, n = 11), and non-SCD controls (n = 13). Hepcidin was found to be inappropriately low, as evidenced by a significantly higher median hepcidin/ferritin ratio in non-SCD controls compared to SCD IO cases (0·3 vs. 0·02, P < 0·0001) and SCD non-IO cases (0·3 vs. 0·02, P < 0·0001), suggesting that certain inhibitory mechanism (s) work to suppress hepcidin in SCD. As opposed to the SCD non-IO state, where hepcidin shows a strong significant positive correlation with ferritin (Spearman ρ = 0·7, P = 0·02), this correlation was lost when IO occurs (Spearman ρ = −0·2, P = 0·4). Although a direct non-linear correlation between erythroferrone (ERFE) and hepcidin did not reach statistical significance both in the IO (Spearman ρ = −0·4, P = 0·08) and non-IO state (Spearman ρ = −0·6, P = 0·07), patients with highest ERFE had low hepcidin levels, suggesting that ERFE contributes to hepcidin regulation in some patients. Our results suggest a multifactorial mechanism of hepcidin regulation in SCD.

Original languageEnglish (US)
Pages (from-to)1204-1209
Number of pages6
JournalBritish Journal of Haematology
Issue number6
StatePublished - Jun 1 2020


  • erythroferrone
  • ferritin
  • hepcidin
  • iron metabolism
  • iron overload
  • sickle cell disease

ASJC Scopus subject areas

  • Hematology


Dive into the research topics of 'Regulation of iron homeostasis through the erythroferrone-hepcidin axis in sickle cell disease'. Together they form a unique fingerprint.

Cite this