Antibodies to endothelial cells in Kawasaki disease lyse endothelial cells without cytokine pretreatment

Abstract

Kawasaki disease (KD) is characterized by diffuse vasculitis and marked immune activation. To confirm the presence of antiendothelial cell antibodies (AECA) and cytotoxicity of AECA, we investigated the presence of AECA using ELISA and cytotoxicity of AECA in KD. Sera from patients with acute KD were assessed for binding to human umbilical vein endothelial cells (HUVEC) using a cell-based ELISA, and for cytotoxicity against HUVEC as indicated by the conversion of a tetrazolium salt (MTT) into a coloured product. IgM AECA were detected in 8/19 KD sera, IgG AECA were detected in 5/19 KD sera. Significant differences in both AECA titres existed between patients and febrile and afebrile controls. Six out of 19 patients showed complement-dependent cytotoxicity against HUVEC. Cytotoxicity was significantly enhanced by pretreating HUVEC with tumour necrosis factor (TNF), and reduced by incubation with gammaglobulin. Serum titres of IgM AECA in the KD patients were positively correlated with cytotoxicity. Findings suggest that IgM AECA mediates complement-dependent cytotoxicity against endothelial cells in patients with KD, and gammaglobulin may reduce complement-dependent cytotoxicity of AECA against endothelial cells.

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