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

Abhishek A. Mangaonkar, Fahim Thawer, James Son, Germame 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

8 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


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