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 © 2005 Wiley-Liss, Inc.

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