Journal of Molecular Medicine

, Volume 89, Issue 8, pp 811–816

Growth differentiation factor 15 in patients with congenital dyserythropoietic anaemia (CDA) type II

  • Guillem Casanovas
  • Dorine W. Swinkels
  • Sandro Altamura
  • Klaus Schwarz
  • Coby M. Laarakkers
  • Hans-Juergen Gross
  • Markus Wiesneth
  • Hermann Heimpel
  • Martina U. Muckenthaler
Original Article

DOI: 10.1007/s00109-011-0751-5

Cite this article as:
Casanovas, G., Swinkels, D.W., Altamura, S. et al. J Mol Med (2011) 89: 811. doi:10.1007/s00109-011-0751-5

Abstract

Congenital dyserythropoietic anaemias (CDAs) are heterogeneous, hereditary disorders hallmarked by ineffective erythropoiesis and tissue iron overload. Growth differentiation factor 15 (GDF15) was suggested to mediate iron overload in iron-loading anaemias, such as the thalassaemias and CDAI by suppressing hepcidin, the key regulator of iron absorption. Here, we show that serum GDF15 concentrations are elevated in subjects with CDAI and CDAII. Despite similar disease characteristics, CDAI patients present with significantly higher GDF15 concentrations compared to CDAII patients. Hepcidin concentrations are inappropriately low in CDAII patients considering the severe hepatic iron overload associated with this disorder. GDF15 significantly correlates with the degree of anaemia (Hb), the response of erythropoiesis (reticulocyte index) as well as with iron availability in the serum (transferrin saturation). The observation that GDF15 is elevated in CDAII patients is consistent with the proposal that GDF15 is among the erythroid factors down-regulating hepcidin and contributing to iron overload in conditions of dyserythropoiesis.

Keywords

Congenital dyserythropoietic anaemia MIC1 PLAB PDF CDAN1 SEC23B 

Supplementary material

109_2011_751_Fig3_ESM.jpg (219 kb)
Supplementary Fig. 1

Soluble transferrin receptor correlations in CDAII patients. Correlations of soluble transferrin receptor with (A) ferritin, (B) the hepcidin to ferritin ratio and (C) hepcidin in CDAII patients (n = 23). Correlations are shown on a logarithmic scale, with the statistical values (ρ and P) indicated. Trend lines are based on the logarithms of the values. (JPEG 218 kb)

109_2011_751_MOESM1_ESM.eps (2.5 mb)
High-resolution image (EPS 2541 kb)
109_2011_751_MOESM2_ESM.pdf (66 kb)
Supplementary Table 1Serum parameters tested in healthy volunteers (1–39) and unaffected family members of CDA patients (40–48). *NA not available (PDF 65 kb)
109_2011_751_MOESM3_ESM.pdf (70 kb)
Supplementary Table 2Representative blood parameters tested in CDAI and CDAII patients. (*) History of splenectomy; (**) iron depletion; (***) regular transfusions. NA not available (PDF 69 kb)
109_2011_751_MOESM4_ESM.pdf (74 kb)
Supplementary Table 3Blood parameters tested in samples from CDAI and CDAII patients. (*) History of splenectomy; (**) receiving iron depletion; (***) regular transfusions. NA not available (PDF 73 kb)
109_2011_751_MOESM5_ESM.pdf (58 kb)
Supplementary Table 4Serum parameters in healthy controls, CDAI and CDAII patients. Mean values and rank (highest and lowest value) are shown. Statistical significance was calculated by a nonparametric Mann–Whitney test. * (number of men/number of women); NS not significant; † reference values are shown for controls (measurements not available). (PDF 57 kb)

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Guillem Casanovas
    • 1
    • 2
    • 3
  • Dorine W. Swinkels
    • 4
  • Sandro Altamura
    • 1
    • 2
  • Klaus Schwarz
    • 5
    • 6
  • Coby M. Laarakkers
    • 4
  • Hans-Juergen Gross
    • 7
  • Markus Wiesneth
    • 5
    • 6
  • Hermann Heimpel
    • 8
  • Martina U. Muckenthaler
    • 1
    • 2
  1. 1.Department of Paediatric Oncology, Haematology and ImmunologyUniversity of HeidelbergHeidelbergGermany
  2. 2.Molecular Medicine Partnership UnitHeidelbergGermany
  3. 3.European Molecular Biology LaboratoryHeidelbergGermany
  4. 4.Department of Laboratory MedicineRadboud University Nijmegen Medical CentreNijmegenthe Netherlands
  5. 5.Institute for Transfusion MedicineUniversity of UlmUlmGermany
  6. 6.Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, German Red Cross, Blood Service Baden-Wuerttemberg-HessenUlmGermany
  7. 7.Central Laboratory of University HospitalsUlmGermany
  8. 8.Department of Internal Medicine IIIUniversity of UlmUlmGermany