Expression of Myeloid-Related Protein-8 and -14 in Patients With Acute Kawasaki Disease

Expression of Myeloid-Related Protein-8 and -14 in Patients With Acute Kawasaki Disease Keiich Hirono, Dirk Foell, Yanlin Xing, Sachiko Miyagawa-Tomita, Fei Ye, Martina Ahlmann, Thomas Vogl, Takeshi Futatani, Chen Rui, Xianyi Yu, Kazuhiro Watanabe, Sayaka Wanatabe, Shinichi Tsubata, Keiichiro Uese, Ikuo Hashimoto, Fukiko Ichida, Makoto Nakazawa, Johannes Roth, Toshio Miyawaki We investigated patients with acute Kawasaki disease to validate myeloid-related protein (MRP)-8/MRP-14 as a marker of disease activity and severity of coronary artery lesion development. The serum MRP-8/MRP-14 levels and messenger ribonucleic acid expressions of MRP-8 and -14 in granulocytes were strongly upregulated before treatment, and decreased dramatically after intravenous immune globulin therapy in all patients, but rebounded at 2 weeks after treatment in nonresponders. The number of MRP-8/MRP-14–positive circulating endothelial cells was higher in Kawasaki disease patients, especially in patients with coronary artery lesions. Serum levels of MRP-8/MRP-14 may be useful markers of disease activity, and the levels of MRP-8/MRP-14–positive circulating endothelial cell may predict the severity of vasculitis. This study investigated patients with acute Kawasaki disease (KD) to validate myeloid-related protein (MRP)-8/MRP-14 as a marker of disease activity and severity of coronary artery lesion development. Both MRP-8 and -14, which are S100-proteins secreted by activated neutrophils and monocytes, bind specifically to endothelial cells and induce thrombogenic and inflammatory responses in a variety of disease conditions. We investigated 61 patients with acute KD and examined sequential changes in serum levels of MRP-8/MRP-14, messenger ribonucleic acid (mRNA) expression of MRP-8 and -14 in circulating granulocytes and monocytes, and amounts of MRP-8/MRP-14 bound to circulating endothelial cells. The serum MRP-8/MRP-14 levels as well as mRNA expressions of MRP-8 and -14 in granulocytes were strongly upregulated during the early stage of acute KD, and decreased dramatically within 24 h of intravenous immune globulin therapy (p < 0.05) in 45 responders. In contrast, in 16 nonresponders both of these increased after the initial treatment. The number of MRP-8/MRP-14–positive circulating endothelial cells was higher in patients with acute KD than in control patients and increased significantly by 2 weeks after the onset of KD, especially in patients in whom coronary artery lesions develo