title: Analysis of tumor necrosis factor-alpha production and polymorphisms of the tumor necrosis factor-alpha gene in individuals with a history of Kawasaki disease.
abstract: BACKGROUND
  Tumor necrosis factor (TNF)-alpha plays a central role in the pathogenesis of vasculitis in Kawasaki disease (KD). To address the genetic background of KD, we investigated the level of TNF-alpha production and genetic polymorphisms in the 5' flanking region of the TNF-alpha gene in healthy children with a history of KD.
  
  
  METHODS
  For TNF-alpha production, peripheral blood mononuclear cells (PBMC) of children with a history of KD (n = 61) and of non-KD children (n = 35) were stimulated with phorbol 12-myristate 13-acetate, toxic shock syndrome toxin-1 (TSST-1) and the culture supernatant of Staphylococcus aureus derived from a KD patient (S-6), which had several superantigenic activities. The genetic background of KD was addressed by studying polymorphisms in the 5' flanking region of the TNF-alpha gene at positions -1031 (thymine (T) to cytosine (C) change, termed -1031C), -863 (C to adenine (A), -863A), -857 (C to T, -857T), -308 (guanine (G) to A, -308A) and -238 (G to A, -238A) in KD, using dot-blot hybridization with sequence-specific oligonucleotide probes.
  
  
  RESULTS
  The PBMC of KD patients with coronary artery lesions produced slightly higher levels of TNF-alpha in response to the bacterial products (such as TSST-1 and S-6). None of the polymorphisms in the 5' flanking region of the TNF-alpha gene were related to KD.
  
  
  CONCLUSIONS
  These results suggest that a genetic disposition towards overproduction of TNF-alpha in response to bacterial products may be involved in the pathogenesis of KD.
authors.affiliation: Department of Pediatrics, Kurume University School of Medicine, Fukuoka, Japan. kamizono@lsi.kurume-u.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Kamizono
authors.forename: A
authors.initials: A
authors.lastname: Yamada
authors.forename: T
authors.initials: T
authors.lastname: Higuchi
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.forename: K
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000293:Adolescent; D000483:Alleles; D002648:Child; D005260:Female; D005796:Genes; D006801:Humans; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000235:genetics*; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha