Measurement of serum growth differentiation factor 15 concentration in children with hemophagocytic lympohistiocytosis and implications in the development of hyperferritinemia

Abstract

Objective To measure the serum growth differentiation factor (GDF15) levels in children with hemophagocytic lympohistiocytosis (HLH), and to explore its possible implications in the development of hyperferritinemia in HLH. Methods Twenty-eight children with newly-diagnosed HLH and 20 age-and-sex matched healthy children were enrolled in this study as research subjects and controls respectively.Serum GDF15 levels were measured by Quantikine ELISA assay (product of R&D Company, USA) according to manufacturer's instructions.Serum ferritin concentration and other biochemical parameters were determined by conventional methods.Comparison of serum GDF15 levels between HLH group and healthy control group were made by nonparametric Mann-Whitney test.Correlations between serum GDF15 concentration and hemobiochemical parameters (Hb, serum ferritin, fibrinogen, blood lipids, and liver and renal function tests) were made via Spearman correlation analysis. Results Serum GDF15 concentration was significantly higher in HLH group than that in healthy control group, with median concentrations and ranges of 1710 ng/L, 190-2400 ng/L, and 260 ng/L, 104-649 ng/L, respectively (P<0.001). Serum GDF15 concentration was correlated neither to Hb concentration at diagnosis nor to lowest Hb concentration before HLH-directed chemotherapy.Nevertheless it was positively correlated to serum level of total bilirubin at diagnosis and highest concentration of trigly-cerates during disease course(χ2=0.475, 0.465; P=0.011, 0.019, respectively), and negatively correlated to lowest levels of fibrinogen and albumin at diagnosis (χ2=-0.423, -0.399; P=0.031, 0.039, respectively). Serum GDF15 level was not correlated to underlying etiology and mortality rate of children with HLH. Conclusions GDF15 has been documented as an upstream negative regulator of hepcidin, the central iron regulatory hormone produced primarily by hepatocytes, and is massively produced by activated macrophages in an autocrine fashion to suppress further activation of macrophages.This research finding that serum GDF15 level is significantly elevated in children with HLH suggests that GDF 15 is intimately implicated in the modulation of iron homeostasis and the development of hyperferritinemia in HLH. Key words: Hemophagocytic lympohistiocytosis; Growth differentiation factor 15; Hyperferritinemia; Child