title: Inflammation-induced hepcidin is associated with the development of anemia and coronary artery lesions in Kawasaki disease.
abstract: OBJECTIVE
  Kawasaki disease (KD) is a systemic febrile vasculitis complicated by coronary artery lesions (CAL). Anemia is common in patients with KD and is associated with a prolonged duration of active inflammation. Hepcidin is a central modulator of inflammation-associated anemia, acting via control of iron absorption and a direct inhibitory effect on erythropoiesis. The aims of this study were to investigate the role of inflammation-induced hepcidin in the development of anemia, the occurrence of CAL formation, and IVIG treatment response in patients with KD.
  
  
  METHODS
  Eighty-six KD patients and 30 febrile controls were enrolled. Levels of interleukin (IL)-6 and serum hepcidin were measured in sera by enzyme-linked immunosorbent assay. Hemoglobin and serum iron levels were also measured.
  
  
  RESULTS
  Hemoglobin and iron levels were lower in KD patients than in controls (p < 0.001 and p = 0.009, respectively). Serum hepcidin and IL-6 levels were higher in KD patients than in controls (both p < 0.001) before intravenous immunoglobulin (IVIG) treatment. After IVIG treatment, serum hepcidin, IL-6, and hemoglobin levels decreased significantly (all p < 0.001). In addition, the serum hepcidin levels before IVIG treatment were negatively correlated with hemoglobin levels after IVIG treatment (R = -0.188, p = 0.046) and positively correlated with the changes of hemoglobin levels after IVIG treatment (R = 0.269, p = 0.015). Furthermore, serum hepcidin levels were negatively correlated with serum iron levels (R = -0.412, p = 0.002), which were positively correlated with hemoglobin levels (R = 0.210, p = 0.045). Additionally, the change of hepcidin levels was associated with IVIG treatment response and the occurrence of CAL formation.
  
  
  CONCLUSIONS
  Inappropriately raised hepcidin levels impair iron metabolism and are associated with decreased hemoglobin levels in KD patients. Inflammation-induced hepcidin is associated with the development of anemia and disease outcomes in patients with KD.
authors.affiliation: Genomic and Proteomic Core Laboratory, Department of Medical Research and Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, Republic of China.
authors.forename: Ho-Chang
authors.initials: HC
authors.lastname: Kuo
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Yang
authors.forename: Jiin-Haur
authors.initials: JH
authors.lastname: Chuang
authors.forename: Mao-Meng
authors.initials: MM
authors.lastname: Tiao
authors.forename: Hong-Ren
authors.initials: HR
authors.lastname: Yu
authors.forename: Li-Tung
authors.initials: LT
authors.lastname: Huang
authors.forename: Kuender D
authors.initials: KD
authors.lastname: Yang
authors.forename: Wei-Chiao
authors.initials: WC
authors.lastname: Chang
authors.forename: Chiu-Ping
authors.initials: CP
authors.lastname: Lee
authors.forename: Ying-Hsien
authors.initials: YH
authors.lastname: Huang
mesh_terms: D000740:Anemia / Q000209:etiology*; D023181:Antimicrobial Cationic Peptides / Q000097:blood* / Q000276:immunology; D003324:Coronary Artery Disease / Q000209:etiology* / Q000276:immunology; D003331:Coronary Vessels; D006454:Hemoglobins / Q000096:biosynthesis; D064451:Hepcidins; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000627:therapeutic use; D015850:Interleukin-6 / Q000097:blood*; D007501:Iron / Q000097:blood; D009080:Mucocutaneous Lymph Node Syndrome / Q000097:blood / Q000150:complications* / Q000276:immunology
chemical_list: D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D006454:Hemoglobins; D064451:Hepcidins; D016756:Immunoglobulins, Intravenous; D015850:Interleukin-6; D007501:Iron