Abstract 2445: Dynamic Change and Pivotal Role of Myeloid-Related Protein (MRP) 8 and MRP14 in Acute Kawasaki Disease
Background: Myeloid-related protein (MRP) 8 and MRP14, 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.
Objective: The aim of our study was to investigate the role of MRP8/MRP14 in acute Kawasaki disease (KD) and to validate MRP8/MRP14 as a marker of disease activity and severity of coronary artery lesion (CAL) development.
Methods: We investigated 61 patients with acute KD differentiated by response to intravenous immune globulin (IVIG) treatment, and examined sequential changes in serum levels of MRP8/MRP14, mRNA expression of MRP8 and MRP14, intracellular expression of MRP8/MRP14 protein, and amounts of MRP8/MRP14 bound to circulating endothelial cells.
Results: The initial serum levels of MRP8/MRP14 were elevated in all patients with KD and decreased within 24 hours of IVIG (P<0.05) in the group of 45 responders. In contrast, in 16 non-responders the serum MRP8/MRP14 levels increased after the initial treatment. mRNA expression of MRP8 and MRP14 were significantly higher in the granulocytes of acute KD responders prior to treatment with IVIG, decreasing significantly within 24 hours of IVIG treatment (P<0.05). The both of expression in non-responders increased after the initial treatment. Intracellular expression of MRP8/MRP14 protein in neutrophils of acute KD patients are markedly higher than that of normal controls, and gradually increased after IVIG treatment in all patients. The number of MRP8/MRP14-positive circulating endothelial cells was higher in patients with acute KD than controls and this increased significantly by 2 weeks after the onset of KD, especially in patients who developed CAL.
Conclusions: We show for the first time that MRP8/MRP14 are exclusively expressed and rapidly secreted by granulocytes in patients with acute KD, and successful IVIG treatment suppresses their gene expression. Serum levels of MRP8/MRP14 may be useful markers of disease activity, and the levels of MRP8/MRP14 positive circulating endothelial cell predict the severity of vasculitis, confirming an important role for distinct inflammatory reactions in endothelium.