title: 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 240.3 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.
authors.affiliation: Department of Pediatrics, Jichi Medical University School of Medicine, Shimotsuke, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Oh
authors.affiliation: Department of Pediatrics, Jichi Medical University School of Medicine, Shimotsuke, Japan. Electronic address: akira@jichi.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Morimoto
authors.affiliation: Division of Pediatric Oncology, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shioda
authors.affiliation: Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Imamura
authors.affiliation: Division of Hematology and Oncology, Shizuoka Children's Hospital, Shizuoka, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kudo
authors.affiliation: The Japan LCH Study Group, Kyoto, Japan.
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Imashuku
mesh_terms: D018925:Chemokines / Q000097:blood; D002648:Child; D002675:Child, Preschool; D006646:Histiocytosis, Langerhans-Cell / Q000097:blood*; D006801:Humans; D007223:Infant; D018836:Inflammation Mediators / Q000378:metabolism; D053495:Osteopontin / Q000097:blood*; D012307:Risk Factors
chemical_list: D018925:Chemokines; D018836:Inflammation Mediators; D053495:Osteopontin
keywords: Infant; Langerhans cell histiocytosis; Multisystem disease; Osteopontin; Serum