Ishii Rumiko, Morimoto Akira, Ikushima Satoshi, Sugimoto Tohru, Asami Keiko, Bessho Fumio, Kudo Kazuko, Tsunematu Yukiko, Fujimoto Junichiro, Imashuku Shinsaku
Department of Pediatrics, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.
Pediatr Blood Cancer. 2006 Aug;47(2):194-9. doi: 10.1002/pbc.20595.
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).
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).
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).
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.
为了确定朗格汉斯细胞组织细胞增多症（LCH）中有用的生化标志物，我们分析了可溶性CD154（sCD154）、白细胞介素2受体（sIL2-R）、核因子κB受体激活剂配体（sRANKL）和骨保护素（OPG）的血清水平。
我们的研究纳入了2002年至2004年间采用JLSG-02方案治疗的46例新诊断的LCH患者（单系统多部位（SM型）：n = 20，多系统多部位（MM型）：n = 26）。患者的中位年龄为3.8岁（范围0 - 18岁）。在诊断时（n = 46）和诱导治疗6周后（n = 14）通过酶联免疫吸附测定法（ELISA）测量sCD154、sIL2-R、sRANKL和OPG。
与对照组相比，LCH患者血清中的sCD154、sIL-2R、sRANKL和OPG的值以及sRANKL/OPG比值显著更高（1.83±1.38对0.22±0.16 ng/ml，P < 0.001；1600±1060对420±160 pg/ml，P < 0.001；1.72±1.20对1.04±1.09 pmol/L，P = 0.019；6.34±2.94对3.71±2.03 pmol/L，P < 0.001；以及0.40±0.45对0.16±0.17，P = 0.023）。与SM型相比，MM型患者血清sIL-2R水平显著升高（2050±1060对870±340 pg/ml，P < 0.001）。与SM型相比，MM型患者血清OPG水平也显著升高（7.58±2.72对5.13±2.69 pmol/L，P = 0.008），且与骨病变数量呈负相关（r = -0.56，P = 0.007）。相反，SM型患者的sRANKL/OPG比值显著高于MM型（0.57±0.54对0.19±0.14，P = 0.002），且与骨病变数量呈正相关（r = 0.34，P = 0.040）。在对诱导治疗有反应的患者中，治疗后血清sIL-2R、sRANKL和OPG水平以及sRANKL/OPG比值显著下降（1170±600对730±290 pg/ml，P = 0.029；2.19±1.06对1.24±0.66 pmol/L，P < 0.001；⑥13±2.40对4.72±2.03 pmol/L，P = 0.040；以及0.57±0.52对0.41±0.37，P = 0.02）。在3例对诱导治疗无反应的患者中，治疗后血清sCD154水平显著升高（1.3±1.1对2.7±1.2，P = 0.004）。
血清sIL-2R和sCD154水平可作为LCH患者炎症的指标，sRANKL/OPG比值可作为溶骨活性的标志物。
Zotero 插件