Soluble ST2 and CD163 as Potential Biomarkers to Differentiate Primary Hemophagocytic Lymphohistiocytosis from Macrophage Activation Syndrome

The differentiation of primary hemophagocytic lymphohistiocytosis (pHLH) and macrophage activation syndrome (MAS) poses a challenge to hematologists. The aim of this study was (1) to compare the levels of soluble ST2 (sST2), sCD163, IFN-gamma, IL-10, IL-18, TNF-alpha and Serum soluble interleukin-2 receptor (sCD25) in patients with pHLH and MAS and (2) to investigate whether they can help differentiate the two diseases. A total of 52 participants were recruited in this study, including 12 pHLH patients, 20 MAS patients, and 20 healthy subjects. We measured the levels of sST2, sCD163 and sCD25 in serum by ELISA. The serum levels of IFN-gamma, IL-10, IL-18, and TNF-alpha were detected using a Luminex 200 instrument. The serum levels of sST2 and sCD163 in MAS patients were markedly higher than that in pHLH patients (363.13 +/- 307.24 ng/ml vs 80.75 +/- 87.04 ng/ml, P = 0.004; 3532.72 +/- 2479.68 ng/ml vs 1731.96 +/- 1262.07 ng/ml, P = 0.046). There was no significant difference in the expression of IFN-gamma (306.89 +/- 281.60 pg/ml vs 562.43 +/- 399.86 pg/ml), IL-10 (20.40 +/- 30.49 pg/ml vs 8.3 +/- 13.14 pg/ml), IL-18 (463.33 +/- 597.04 pg/ml vs 1247.82 +/- 1318.58 pg/ml), TNF-alpha (61.48 +/- 84.69 pg/ml vs 106.10 +/- 77.21 pg/ml), and sCD25 (21062.1 +/- 18515.26 pg/ml vs 11074.78 +/- 11149.96 pg/ml) between pHLH and MAS. Patients with pHLH and MAS show some differences in cytokine profiles. The elevated levels of IFN-gamma, IL- 10, TNF-alpha, IL-18, and sCD25 can contribute to the diagnosis of HLH, but may not discriminate pHLH from MAS. Levels of sST2 and sCD163 may serve as markers to distinguish pHLH from MAS.