Increased Levels of Plasma Pentraxin 3 Predict IVIG Resistance and CoronaryArtery Lesion Formation in Patients with Kawasaki Disease
2Department of Pediatrics, Aichi Medical University, School of Medicine
3Department of Lifelong Sports and Health Sciences, Chubu University College of Life and Health Sciences
4Division of Clinical Pharmacy, Kobe Gakuin University, Faculty of Pharmaceutical Sciences
5Department of Quantitative Biology and Medicine, Research Center for Advanced Science and Technology, the University of Tokyo
Background: Kawasaki disease (KD) is a systemic vasculitis and childhood febrile disease that can lead to cardiovascular complications. Delaying definitive diagnosis of KD and intravenous immunoglobulin (IVIG) or specific treatment leads to development of coronary artery lesion (CAL). However, there are no specific biomarkers for KD definitive diagnosis in clinical settings. Objective: To determine whether novel biomarkers for endothelial cell damage are accurate markers of inflammation in KD, and whether plasma levels of these markers correlate with resistance to initial IVIG and the development of coronary artery lesions (CAL) in KD.
Methods: In this prospective study of 97 children with KD (75 complete KD and 22 incomplete KD, 94 without CAL and 3 with CAL), recurrence 3 cases IVIG resistant 22, IVIG responsive; 63 cases, no IVIG; 12 case. Plasma pentraxin 3 (PTX3), soluble lectin-like oxidised low-density lipoprotein receptor-1 (sLOX-1), and matrix metalloproteinase-9 (MMP-9) concentrations were analysed at three clinical points: (a) up to IVIG treatment, (b) after IVIG treatment, and (c) during convalescence after fever resolution and compared with linical outcome; IVIG resistance and transient or ultimate CAL fromation detected by Echocardiogram.
Results: Increases in levels of plasma PTX3 were only significantly higher compared with non-KD febrile controls. PTX3 level was significantly higher in IVIG non-responders than in IVIG responders (p< 0.001). PTX3 level was significantly correlated with the number of courses of IVIG treatment needed to resolve fever. (p< 0.001). The patients with CAL had higher PTX3 levels than patients without CAL (85 ± 8.4 vs. 22 ± 2.2 ng/ml, p< 0.0001). The cut-off value of 69 ng/ml to predict CAL formation had a specificity of 1.00, sensitivity of 0.98, and likelihood ratio of 49.0.
Conclusions: Levels of PTX3 were correlated with the severity of Kawasaki disease. A PTX3 level above 69 ng/ml predicted CAL formation. These data suggest that PTX3 can be a definitive biomarker for prediction of IVIG resistance and subsequent CAL formation in patients with Kawasaki disease.
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