title: Th17- and Treg-related cytokine and mRNA expression are associated with acute and resolving Kawasaki disease.
abstract: BACKGROUND
  Kawasaki disease is a vasculitis most commonly afflicting children <5 years of age. Many autoimmune diseases are associated with up-regulation of T helper (Th) 17 cells, and down-regulation Treg cells. Few studies have examined the Th17/Treg expression in Kawasaki disease.
  
  
  METHODS
  Blood samples were obtained from 186 children with Kawasaki disease at 24 h before IVIG therapy, followed by 3 days and 21 days after IVIG therapy. Thirty children with an acute febrile infectious disease and 30 healthy children were obtained as control. Plasma levels of Th17- and Treg-related cytokines including IL-6, IL-17A, IL-10, TGF-β, and mRNA expression levels of RORγt and Foxp3 were tested.
  
  
  RESULTS
  Patients with Kawasaki disease had higher levels of plasma IL-17A (25.35 ± 3.21 vs 7.78 ± 1.78 pg/ml, P < 0.001) and IL-6 (152.29 ± 21.94 vs 38.63 ± 12.40 pg/ml, P < 0.001) when compared to the febrile control group. IVIG resulted in a reduction in IL-6 and IL-17A at both 3 and 21 days after IVIG therapy. FoxP3 levels increased significantly 3 days after IVIG therapy (2.28 ± 0.34 vs 0.88 ± 0.14, P < 0.001). IVIG resistance was associated with higher levels of IL-10 and IL-17A.
  
  
  CONCLUSIONS
  Kawasaki disease was associated with higher IL-17A and IL-6, a cytokine profile similar to other autoimmune diseases. IVIG therapy resulted in increased expression of Treg-related FoxP3. IVIG resistance was associated with higher levels of IL-10 and IL-17A. Our findings provide further evidence that Kawasaki disease is an autoimmune-like disease.
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: M M-H
authors.initials: MM
authors.lastname: Guo
authors.forename: W-N
authors.initials: WN
authors.lastname: Tseng
authors.forename: C-H
authors.initials: CH
authors.lastname: Ko
authors.forename: H-M
authors.initials: HM
authors.lastname: Pan
authors.forename: K-S
authors.initials: KS
authors.lastname: Hsieh
authors.forename: H-C
authors.initials: HC
authors.lastname: Kuo
mesh_terms: D018791:CD4 Lymphocyte Count; D002675:Child, Preschool; D003324:Coronary Artery Disease / Q000150:complications; D016207:Cytokines / Q000097:blood* / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D016130:Immunophenotyping; D007223:Infant; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016756:Immunoglobulins, Intravenous; D012333:RNA, Messenger
keywords: Kawasaki disease; T-helper 17 cells; cytokines; intravenous immunoglobulin resistance; regulatory T cells