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

Rumiko Ishii, Akira Morimoto, Satoshi Ikushima, Tohru Sugimoto, Keiko Asami, Fumio Bessho, Kazuko Kudo, Yukiko Tsunematu, Junichiro Fujimoto, Shinsaku Imashuku

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33 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)194-199
Number of pages6
JournalPediatric Blood and Cancer
Volume47
Issue number2
DOIs
Publication statusPublished - 08-2006

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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