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

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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.