title: Disruption of vascular endothelial homeostasis in systemic juvenile idiopathic arthritis-associated macrophage activation syndrome: The dynamic roles of angiopoietin-1 and -2.
abstract: To assess the role of angiopoietin (Ang)-1 and Ang-2 and to investigate the clinical significance of serum levels of them in systemic juvenile idiopathic arthritis (s-JIA)-associated macrophage activation syndrome (MAS), we determined these levels in 51 patients with s-JIA, 11 patients with polyarticular JIA (poly-JIA), 12 patients with virus associated hemophagocytic syndrome (VAHS), 12 patients with Kawasaki disease (KD), and 15 age-matched healthy controls (HC). The results were compared with clinical features of MAS. During the MAS phase, serum Ang-1 levels were significantly decreased compared with those during the active and inactive phases. Serum Ang-2/1 ratio were significantly elevated during the MAS phase, compared with those during the active and inactive phases. There was a rapid increase in the Ang-2/1 ratio at the onset of MAS. Serum Ang-1 and the Ang-2/1 ratio significantly correlated with measures of disease activity, including AST and LDH. Ang-2/1 dysregulation was also observed in patients with VAHS, whereas not observed in most cases of KD. The homeostasis of vascular endothelial function by Ang-1 and Ang-2 is disrupted in MAS. Serum Ang-1 levels and the Ang-2/1 ratio might represent promising indicators of disease activity for MAS.
authors.affiliation: Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tasaki
authors.affiliation: Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Japan. Electronic address: shimizum@staff.kanazawa-u.ac.jp.
authors.forename: Masaki
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Inoue
authors.affiliation: Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Japan.
authors.forename: Mao
authors.initials: M
authors.lastname: Mizuta
authors.affiliation: Department of Pediatric Rheumatology, Hyogo Prefectural Kobe Children's Hospital, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Nakagishi
authors.affiliation: Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Japan.
authors.forename: Taizo
authors.initials: T
authors.lastname: Wada
authors.affiliation: Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yachie
mesh_terms: D000293:Adolescent; D042683:Angiopoietin-1 / Q000097:blood* / Q000502:physiology; D042702:Angiopoietin-2 / Q000097:blood* / Q000502:physiology; D001171:Arthritis, Juvenile / Q000150:complications / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006706:Homeostasis; D006801:Humans; D007223:Infant; D051359:Lymphohistiocytosis, Hemophagocytic / Q000503:physiopathology / Q000821:virology; D055501:Macrophage Activation Syndrome / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000503:physiopathology
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D016207:Cytokines
keywords: Angiopoietin 1; Angiopoietin 2; Endothelial function; Macrophage activation syndrome; Systemic juvenile idiopathic arthritis