Regulation of iron metabolism through GDF15 and hepcidin in pyruvate kinase deficiency.
Iron absorption is inadequately increased in patients with chronic haemolytic anaemia, which is commonly complicated by iron overload. Growth differentiation factor 15 (GDF15) has been identified as a bone marrow-derived factor that abrogates hepcidin-mediated protection from iron overload under conditions of increased erythropoiesis. Increased concentrations of GDF15 have been reported in beta-thalassaemia patients and GDF15 has been found to suppress hepcidin expression in vitro. To further study the interdependencies of iron metabolism and erythropoiesis in vivo, the concentrations of hepcidin and GDF15 were determined in sera from 22 patients with pyruvate kinase deficiency (PKD) and 21 healthy control subjects. In PKD patients, serum hepcidin levels were 13-fold lower than in controls (2.0 ng/ml vs. 26.2 ng/ml) and GDF15 was significantly higher (859 pg/ml vs. 528 pg/ml). Serum hepcidin concentrations correlated positively with haemoglobin and negatively with serum GDF15. These results suggest that GDF15 contributes to low hepcidin expression and iron loading in PKD.
Finkenstedt
Armin
A
Department of Medicine II, Medical University of Innsbruck, Innsbruck, Austria.
Bianchi
Paola
P
Theurl
Igor
I
Vogel
Wolfgang
W
Witcher
Derrick R
DR
Wroblewski
Victor J
VJ
Murphy
Anthony T
AT
Zanella
Alberto
A
Zoller
Heinz
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D023181:Antimicrobial Cationic Peptides / Q000097:blood* / Q000378:metabolism; D016022:Case-Control Studies; D004920:Erythropoiesis / Q000502:physiology; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood* / Q000378:metabolism; D006454:Hemoglobins / Q000032:analysis; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011770:Pyruvate Kinase / Q000172:deficiency*; D017701:Reticulocyte Count; D018709:Statistics, Nonparametric; D055815:Young Adult
D023181:Antimicrobial Cationic Peptides; D055436:Growth Differentiation Factor 15; C578702:HAMP protein, human; D006454:Hemoglobins; D064451:Hepcidins; D007501:Iron; D011770:Pyruvate Kinase