Analysis of tumor necrosis factor-alpha production and polymorphisms of the tumor necrosis factor-alpha gene in individuals with a history of Kawasaki disease.
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.
Kamizono
S
S
Department of Pediatrics, Kurume University School of Medicine, Fukuoka, Japan. kamizono@lsi.kurume-u.ac.jp
Yamada
A
A
Higuchi
T
T
Kato
H
H
Itoh
K
K
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*
D014409:Tumor Necrosis Factor-alpha