BACKGROUND AND OBJECTIVES : Anti-endothelial cell antibodies (AECA) are found in the sera of many patients with Kawasaki disease (KD). In this study, the pathogenic role of AECA in the development of coronary arterial lesions of KD was investigated. SUBJECTS AND METHODS : Serum IgM-AECA concentrations were measured in 22 KD patients. Cultured human coronary artery endothelial cells (HCAEC) were incubated with either acute or convalescent phase sera, and their expressions of intercellular adhesion molecule-1 (ICAM-1) assessed. IgM fractions of the sera were purified, and their ability to induce ICAM-1 mRNA and protein expressions evaluated. To address the signal transduction pathways involved in IgM-AECA-induced ICAM-1 expression, the blocking effect of four protein kinase inhibitors, PD98059, SB203580, dimethylaminopurine (DMAP) and parthenolide were measured. RESULTS : IgM-AECA was present in 14 out of 22 (64%) acute KD sera. ICAM-1 expression of HCAEC incubated with acute KD sera (117.1+/-46.7) and AECA-positive acute KD sera (143.3+/-37.5) were significantly higher than those of the convalescent KD sera (88.9+/-14.4, p<0.05) or AECA-negative acute KD sera (71.2+/-11.8, p<0.05), respectively. IgM-AECA from KD patients significantly induced ICAM-1 protein and mRNA expression. The upregulation of ICAM-1 expression was significantly inhibited by SB203580, DMAP and parthenolide, but not by PD98059. CONCLUSION : IgM-AECA was detected in the sera of about 2/3 of acute KD patients, which activated endothelial cells by upregulation of ICAM-1 expression, possibly via p38, JNK MAPK and NF-kappaB signal transduction pathways. Thus, IgM-AECA may play a pathogenic role in the development of coronary arterial lesions in KD patients.
Antibodies ; Coronary Vessel Anomalies ; Coronary Vessels ; Endothelial Cells ; Humans ; Immunoglobulin M ; Intercellular Adhesion Molecule-1 ; Mucocutaneous Lymph Node Syndrome* ; NF-kappa B ; Protein Kinase Inhibitors ; RNA, Messenger ; Signal Transduction ; Up-Regulation

A procedure descried by Fontan and Baudet in 1971 successfully bypassed the right ventricle in Tricuspid Atresia patients, after then many modification of the Fontan operation had been described and applied to many cyanotic complex heart patients. Forty patients with a variety of cardiac malformation underwent the Fontan operation at Seoul National University hospital (September 1978 to June 1986). The age at operation ranged 2 months to 18 years. Each number of cases according to basic cardiac anomaly was as follows; 17 in Tricuspid Atresia, 17 in Univertricular Heart, 2 in Double outlet of Right Ventricle, 2 in Transposition of the Great Arteries and 2 in Criss-cross heart. Total mortality rate after the Fontan operation was 50%. There was only one late death (>30 days). Mortality rate under 4 years of age (67%) was higher than that between 4 and 18 years of age (40%). we observed a significantly higher mortality for patients who, in the immediate postoperative period, had central venous pressure greater than 25cm H2O. 45% among survivals did not require further medication. Although mortality rate after the Fontan operation is much higher than that in the foreign literature, operative mortality will decline with the increased expirence of surgeon and the effective patients selection.
Arteries ; Central Venous Pressure ; Crisscross Heart ; Fontan Procedure* ; Heart ; Heart Ventricles ; Humans ; Mortality ; Postoperative Period ; Seoul ; Tricuspid Atresia