High serum values of soluble CD154, IL‐2 receptor, RANKL and osteoprotegerin in Langerhans cell histiocytosis

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Abstract
Background: To determine useful biochemical markers in Langerhans cell histiocytosis (LCH), we analyzed the serum levels of soluble CD154 (sCD154), IL2 receptor (sIL2‐R), receptor activator of NF‐κB ligand (sRANKL), and osteoprotegerin (OPG).Procedure: Our study included 46 newly diagnosed LCH patients (single‐system multi‐site (SM type): n = 20, and multi‐system multi‐site (MM type): n = 26) who were treated with the JLSG‐02 protocol between 2002 and 2004. The median age of the patients was 3.8 years old (range 0–18). sCD154, sIL2‐R, sRANKL, and OPG were measured by ELISA at diagnosis (n = 46) and after 6‐weeks of induction therapy (n = 14).Results: The values of sCD154, sIL‐2R, sRANKL, and OPG, and the sRANKL/OPG ratio in sera were significantly higher in patients with LCH compared with controls (1.83 ± 1.38 vs. 0.22 ± 0.16 ng/ml, P < 0.001; 1,600 ± 1,060 vs. 420 ± 160 pg/ml, P < 0.001; 1.72 ± 1.20 vs. 1.04 ± 1.09 pmol/L, P = 0.019; 6.34 ± 2.94 vs. 3.71 ± 2.03 pmol/L, P < 0.001; and 0.40 ± 0.45 vs. 0.16 ± 0.17, P = 0.023, respectively). Serum levels of sIL‐2R were significantly elevated in the MM type compared with the SM type (2,050 ± 1,060 vs. 870 ± 340 pg/ml, P < 0.001). Serum OPG levels were also significantly elevated in the MM type compared with the SM type (7.58 ± 2.72 vs. 5.13 ± 2.69 pmol/L, P = 0.008) and negatively correlated with the number of bone lesions (r = −0.56, P = 0.007). In contrast, the sRANKL/OPG ratios were significantly higher in the SM type than the MM type (0.57 ± 0.54 vs. 0.19 ± 0.14, P = 0.002) and positively correlated with the number of bone lesions (r = 0.34, P = 0.040). In patients who responded to the induction therapy, serum levels of sIL‐2R, sRANKL, and OPG, and the sRANKL/OPG ratio decreased significantly after the therapy (1,170 ± 600 vs. 730 ± 290 pg/ml, P = 0.029; 2.19 ± 1.06 vs. 1.24 ± 0.66 pmol/L, P < 0.001; 6.13 ± 2.40 vs. 4.72 ± 2.03 pmol/L, P = 0.040; and 0.57 ± 0.52 vs. 0.41 ± 0.37, P = 0.02, respectively). In the three patients who did not respond to the induction therapy, the serum levels of sCD154 increased significantly after the therapy (1.3 ± 1.1 vs. 2.7 ± 1.2, P = 0.004).Conclusions: Serum levels of sIL‐2R and sCD154 could be useful as indicators of inflammation and sRANKL/OPG ratios as markers of osteolytic activity in LCH patients. Pediatr Blood Cancer