PS1292 LINK BETWEEN IRON AND TRYPTOPHAN METABOLISM OBSERVED IN INDIVIDUALS WITH IRON DEFICIENCY AND ANEMIA
Authors: D. Enko, A. Meinitzer, G. Kriegshäuser, G. Baumann, W.J. Schnedl, S. Zelzer, H. Mangge, M. Herrmann, S.J. Holasek, J. Wenninger
Journal: HemaSphere (2019)

Background: Blood transfusions make significant contribution to iron overload in patients with myelodysplastic syndrome. However, the excess iron accumulation is observed even on the early stage of disease, before repeated blood transfusions. During this compensatory response, the excess production of GDF 15 suppresses the hepcidin synthesis and provides an increasing iron availability for erythropoiesis by rising an iron absorption and iron releasing from macrophages. Such effect becomes more significant in non-effective erythropoiesis, in which erythroid precursors undergo apoptosis, not maturation. As a result, the hepcidin deficiency leads to iron overload in absence of transfusion dependence. Aims: To analyze the ferritin and hepcidin serum levels in patients with myelodysplastic syndrome in accordance with transfusion burden. Methods: 22 patients with myelodysplastic syndrome were enrolled in the study. According to IPSS criteria, there were four patients (18,2%) with low risk MDS, two patients (9,1%) with intermediate-2 risk and 16 patients (72,2%) with intermediate-1 risk. In accordance with WPSS, 14 (63,6%) patients were RBC transfusion-dependent and 8 (36,4%) patients were transfusion-independent. The ferritin and hepcidin serum levels were measured by ELISA method. The findings from healthy controls (n = 18) were used to evaluate the hepcidin level. Results: The average level of ferritin in the group of MDS patients was 624,5 ± 194,89 ng/ml, that was 8-fold higher the controls group (70,39 ± 65,7ng/ml; p < 0,001). The positive correlation between the annual transfusion burden and ferritin serum level demonstrated the important role of multiple blood transfusion in the development of iron overload syndrome (r = 0,4, p < 0,05, n = 22). The average hepcidin serum level in patients group was 51,12 ± 26,46 ng/ml, that was 2,4-fold higher the controls group (22,8 ± 20,97 ng/ml). Thus, in presence of the excess iron accumulation the hepcidin serum level is increasing together with the ferritin level as attempt to suppress to cell iron export in the excess iron accumulation. To evaluate the relationship between ferritin and hepcidin serum level, we estimated the correlation between these markers in patients, divided on three subgroups according to annual transfusion burden (similarly to the work done by Niraj Shenoy, 2014). There was a strong positive correlation between hepcidin and ferritin serum level (r = 0,96 (n = 6,p < 0,001)) in the subgroup of patients who received less than 9 RBC units. There was no correlation (r = 0,009 (n = 9, p>0,05) in those patients who received from 9 to 24 RBC units per year and the negative correlation between these markers was observed in subgroup of patients who received more than 24 RBC units per year (r = −0,55 (n = 7, p>0,05). Therefore, the hepcidin serum level remains sensitive to the iron serum level in patients with relatively low transfusion dependence. Multiple RBC transfusions lead to activation of circulating hepcidin, but its level is inadequate in relation to the level of excess iron accumulation. Summary/Conclusion: The patients with low- and intermediate risk of myelodysplastic syndrome and with relatively low degree of transfusion dependence probably are more susceptible to excess iron accumulation not due to the repeated blood transfusions, but because of the development non-transfusional iron overload and inappropriate hepcidin synthesis.