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

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 240.3. ng/ml (137.6-456.0) in MS+ (. n=. 8); 92.7. ng/ml (62.0-213.8) in MS- (. n=. 14) and 72.5. ng/ml (55.6-94.0) in SS (. n=. 9) and 74.4. ng/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 56.2. ng/ml (22.9-77.5) in MS- (. n=. 13), 58.9. ng/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.