Abstract O.33: Identification of Kawasaki Disease-specific Molecules in the Sera as Microbe-associated Molecular Patterns
Background: Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. The innate immune system is involved in its pathophysiology at the acute phase. We have recently established a novel murine model of KD coronary arteritis by oral administration of a synthetic microbe-associated molecular pattern (MAMP). On the hypothesis that specific MAMPs exist in KD sera, we have searched them to identify KD-specific molecules and to assess the pathogenesis.
Methods: The study subjects included 117 patients with KD (median age, 21 months; range 3-96 months; male/female, 65/52) and 101 controls with other febrile illnesses (DC: median age, 16 months; range 0-121 months; male/female, 61/40), and 5 normal controls (NC: median age, 6 months; range 3-39 months; male/female, 1/4). We performed liquid chromatography-mass spectrometry (LC-MS) analysis of fractionated serum and microbial samples by ethyl acetate.
Results: KD serum samples elicited proinflammatory cytokine responses from human coronary artery endothelial cells (HCAECs). By LC-MS analysis of KD serum samples collected at 3 different periods, we detected a variety of KD-specific molecules in the lipophilic fractions that showed distinct m/z and MS/MS fragmentation patterns in each cluster. Serum KD-specific molecules showed m/z and MS/MS fragmentation patterns almost identical to those of MAMPs obtained from Bacillus cereus, Yersinia pseudotuberculosis and Staphylococcus aureus at the 1st study period, and from MAMPs from Bacillus cereus, Bacillus subtilis/Bacillus cereus/Yersinia pseudotuberculosis and Staphylococcus aureus at the 2nd and 3rd periods. These molecules decreased after intravenous immunoglobulin (IVIG) treatment.
Conclusions: We herein conclude that serum KD-specific molecules possess molecular structures common to MAMPs from Bacillus cereus, Bacillus subtilis, Yersinia pseudotuberculosis and Staphylococcus aureus. Discovery of these KD-specific molecules offers novel insight into the diagnosis and management of KD as well as its pathogenesis.
Author Disclosures: T. Kusuda: None. Y. Nakashima: None. K. Murata: None. S. Kanno: None. Y. Mizuno: None. K. Ouchi: None. K. Waki: None. T. Hara: None.
- © 2015 by American Heart Association, Inc.