Serum hepcidin measured with an improved ELISA correlates with parameters of iron metabolism in patients with myelodysplastic syndrome

Abstract

Patients with myelodysplastic syndromes (MDS) often show elevated serum ferritin levels at diagnosis, probably caused by increased intestinal iron uptake attributable to ineffective erythropoiesis. Many patients also develop transfusional iron overload. Hepcidin, a pivotal regulator of iron homeostasis, controls iron uptake in the duodenum as well as iron release from macrophages and is potentially involved in iron distribution to different organs. We measured serum hepcidin, together with other laboratory parameters related to iron metabolism and hematopoiesis (ferritin, transferrin, transferrin saturation, soluble transferrin receptor, erythropoietin, and hemoglobin), and C-reactive protein as marker of inflammation, in 89 MDS patients. Hepcidin levels were measured with two different competitive ELISAs: (a) EIA-4705 as described by Schwarz et al. (J Gastroenterol 46:648-656; 2011) and (b) Hepcidin 25 bioactive ELISA (EIA-5258), which was develop by DRG Diagnostics, Marburg, in 2012. Median hepcidin levels with EIA-5258 were as follows: entire cohort 17.5 ng/ml (n = 89), RA/RARS 5.9 ng/ml (n = 5), RCMD 17.8 ng/ml (n = 38), RS-RCMD 8.7 ng/ml (n = 7), RAEB I/II 29.1 ng/ml (n = 22), CMML I/II 16.9 ng/ml (n = 10), and MDS with del(5q) 26.3 ng/ml (n = 7). Hepcidin levels of the RA/RARS patients were significantly lower than in the other groups except RS-RCMD. RS-RCMD had significantly lower levels than RAEB and 5q- patients. There was a positive correlation between hepcidin levels and serum ferritin and transferrin saturation, and a negative correlation between hepcidin and hemoglobin and transferrin. Malcovati et al. (Blood 112:2676a, 2008), Santini et al. (PLoS One 6:e23109, 2011), and Ambaglio et al. (Haematologica 98:420-423, 2013), using mass spectrometry, reported similar results. We further assessed transfusional status and could show that patients who had been transfused have significantly higher hepcidin levels (median 33.3 versus 8.8 ng/ml (p < 0.001)). A dichotomized hepcidin level correlated with worse survival. EIA-4705 as described by Schwarz showed no correlation with markers of iron metabolism. Measurement of serum hepcidin with an improved ELISA yield results that correlate with other parameters of iron metabolism as well as survival and transfusion needs.