Yasutaka Nakashima, Yasunari Sakai, Yumi Mizuno, Kenji Furuno, Kenji Hamase, Tomofumi Miyamoto, Kenichiro Yamamura, Hisanori Nishio, Hidetoshi Takada, Shouichi Ohga, Toshiro Hara
OBJECTIVE: Coronary arteritis is a life-threatening complication of Kawasaki disease (KD), the leading cause of systemic vasculitis in childhood. Various microorganisms and microbe-derived molecules have been reported to cause KD. However, little is known about the key molecules that contribute to the development of coronary arteritis in KD. We performed a comprehensive lipidomic analysis to identify the molecules that can cause coronary arteritis in KD. METHOD: We prospectively recruited 105 patients with KD and 65 disease controls in 4 different parts of Japan from 2015 to 2018. During this period, we conducted lipidomics analyses of their sera using liquid chromatography (LC)-mass spectrometry (MS). After exploration of KD-specific molecules, the molecules were further analyzed in terms of the association with clinical features and the molecular structures. RESULT: The comprehensive LC-MS system detected a total of 27,776 molecules harboring the unique retention time and m/z values. In the first cohort of 57 KD patients, we found that a fraction of these molecules showed enrichment patterns that varied with the sampling region and season. Among them, 28 molecules were recurrently detected in KD patients, but not in controls. The second and third cohorts of 48 more patients with KD revealed that these KD specific molecules were correlated with inflammatory markers (leukocyte counts and C-reactive proteins) in the acute phase. Notably, two of these molecules were significantly associated with the development of coronary arteritis in the acute phase of KD. Their fragmentation patterns in the tandem MS/MS analysis were consistent with those of atherosclerosis-associated molecules. Furthermore, the concentrations of lectin-like oxidized low-density lipoprotein receptor-1 ligand containing apolipoprotein B in the plasma of KD patients were significantly higher than in controls. CONCLUSION: This study has revealed that activated atherogenic signals are involved in the pathogenesis of coronary arteritis in KD.