title: High serum values of soluble CD154, IL-2 receptor, RANKL and osteoprotegerin in Langerhans cell histiocytosis.
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-kappaB ligand (sRANKL), and osteoprotegerin (OPG).
  
  
  METHODS
  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.
authors.affiliation: Department of Pediatrics, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan. rumiko@koto.kpu-m.ac.jp
authors.forename: Rumiko
authors.initials: R
authors.lastname: Ishii
authors.forename: Akira
authors.initials: A
authors.lastname: Morimoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ikushima
authors.forename: Tohru
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Keiko
authors.initials: K
authors.lastname: Asami
authors.forename: Fumio
authors.initials: F
authors.lastname: Bessho
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kudo
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Tsunematu
authors.forename: Junichiro
authors.initials: J
authors.lastname: Fujimoto
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Imashuku
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D023201:CD40 Ligand / Q000097:blood*; D002352:Carrier Proteins / Q000097:blood*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006646:Histiocytosis, Langerhans-Cell / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood*; D015375:Receptors, Interleukin-2 / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D015375:Receptors, Interleukin-2; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D023201:CD40 Ligand