Analysis of tumor necrosis factor-α production and polymorphisms of the tumor necrosis factor-α gene in individuals with a history of Kawasaki disease.

Autor: Kamizono, Shintaro, Yamada, Akira, Higuchi, Takafumi, Kato, Hirohisa, Itoh, Kyogo
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Zdroj: Pediatrics International; Aug99, Vol. 41 Issue 4, p341-345, 5p
Abstrakt: Abstract Background: Tumor necrosis factor (TNF)-α 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-α production and genetic polymorphisms in the 5′ flanking region of the TNF-α gene in healthy children with a history of KD. Methods: For TNF-α 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-α 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-α 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-α gene were related to KD. Conclusions: These results suggest that a genetic disposition towards overproduction of TNF-α in response to bacterial products may be involved in the pathogenesis of KD. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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