High serum osteopontin levels in pediatric patients with high risk Langerhans cell histiocytosis

Abstract

Osteopontin (OPN) acts as an osteoclast activator, a proinflammatory cytokine, and a chemokine attracting histiocytes/monocytes and is abundantly expressed in Langerhans cell histiocytosis (LCH). We investigated whether serum OPN levels are related to disease types in LCH. Fifty-eight newly diagnosed LCH patients were studied; eight with risk organ (liver, spleen and/or hematopoietic) involvements positive multisystem (MS+) disease, 27 with risk organ involvement negative multisystem (MS−) disease and 23 with single system (SS) disease. Pediatric patients with non-inflammatory disease (n=27) were used as controls. All of patients with MS+ disease were younger than 3 years. Serum OPN levels and 44 kinds of humoral factors were measured by ELISA and Bio-Plex suspension array system, respectively. In the patients younger than 3 years, the median serum OPN level (interquartile range) was 240.3ng/ml (137.6–456.0) in MS+ (n=8); 92.7ng/ml (62.0–213.8) in MS− (n=14) and 72.5ng/ml (55.6–94.0) in SS (n=9) and 74.4ng/ml (42.2–100.0) in control (n=12). The OPN values were significantly higher in the MS+ group than the MS−, SS and control groups (p=0.044, p=0.001 and p=0.002, respectively), but not different between the MS−, SS and control groups. In the patients older than 3 years, the median level of serum OPN (IQR) was 56.2ng/ml (22.9–77.5) in MS− (n=13), 58.9ng/ml (31.0–78.7) in SS (n=14) and 41.9 (28.9–54.1) in control (n=15). These values did not differ significantly between each group. The serum OPN levels were positively correlated with the serum IL-6, CCL2, IL-18, IL-8 and IL-2 receptor concentration. OPN may be involved in risk organ dissemination and poor prognosis of LCH through the function as inflammatory cytokine/chemokine.