Abstract
Kawasaki disease (KD) is the leading cause of acquired heart disease during childhood in the developed countries. Coronary artery lesions (CAL) are the major complications of KD. A unique proteomic profiling with increased or decreased fibrinogen, alpha-1-antitrypsin, clusterin, and immunoglobulin free light chains were noted in KD in our previous study. The purpose of this study was to evaluate relations between these biomarkers and CAL in KD and to establish within the markers the appropriate cut-off value with which to predict the occurrence of CAL. A total of 47 KD patients were enrolled, including 14 with CAL and 33 without CAL. Plasma samples from patients with KD before intravenous immunoglobulin administration were indicated for measurement of these biomarkers. A potential relation among CAL, clinical characteristics, and these biomarkers was investigated, and a receiver operating characteristic curve was used to identify a cut-off value of the significant marker that best predicated the occurrence of CAL. Among these biomarkers, only plasma clusterin level was associated with the occurrence of CAL. Using a cut-off value of clusterin <12.0 mg/l, the relative risk for CAL was 4.53-fold (95% confidence interval [CI] 1.060–19.347%, P = 0.014). Results from this study suggest that plasma clusterin level <12.0 mg/l in KD is significantly associated with the occurrence of CAL. Results from this study provide a potential biomarker of KD that may help predict the occurrence of CAL.
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Ban JY, Yoon KL, Kim SK, Kang S, Chung JH (2009) Promoter polymorphism (rs3755724, -55C/T) of tissue inhibitor of metalloproteinase 4 (TIMP4) as a risk factor for Kawasaki disease with coronary artery lesions in a Korean population. Pediatr Cardiol 30:331–335
Biezeveld MH, Kuipers IM, Geissler J, Lam J, Ottenkamp JJ, Hack CE et al (2003) Association of mannose-binding lectin genotype with cardiovascular abnormalities in Kawasaki disease. Lancet 361:1268–1270
Cabana VG, Gidding SS, Getz GS, Chapman J, Shulman ST (1997) Serum amyloid A and high density lipoprotein participate in the acute phase response of Kawasaki disease. Pediatr Res 42:651–655
Cheung YF, Yung TC, Tam SC, Ho MH, Chau AK (2004) Novel and traditional cardiovascular risk factors in children after Kawasaki disease: implications for premature atherosclerosis. J Am Coll Cardiol 43:120–124
Huang SM, Weng KP, Chang JS, Lee WY, Huang SH, Hsieh KS (2008) Effects of statin therapy in children complicated with coronary arterial abnormality late after Kawasaki disease: a pilot study. Circ J 72:1583–1587
Ishikawa Y, Akasaka Y, Ishii T, Komiyama K, Masuda S, Asuwa N et al (1998) Distribution and synthesis of apolipoprotein J in the atherosclerotic aorta. Arterioscler Thromb Vasc Biol 18:665–672
Jenne DE, Lowin B, Peitsch MC, Böttcher A, Schmitz G, Tschopp J (1991) Clusterin (complement lysis inhibitor) forms a high density lipoprotein complex with apolipoprotein A-I in human plasma. J Biol Chem 266:11030–11036
Kim T, Choi W, Woo CW, Choi B, Lee J, Lee K et al (2007) Predictive risk factors for coronary artery abnormalities in Kawasaki disease. Eur J Pediatr 166:421–425
Krijnen PA, Niessen HW (2007) The antiapoptotic protein clusterin protects cardiomyocytes against ischemia-induced cell death. Am J Physiol Heart Circ Physiol 293:H3223–H3224
Kuo HC, Yang KD, Liang CD, Bong CN, Yu HR, Wang L et al (2007) The relationship of eosinophilia to intravenous immunoglobulin treatment failure in Kawasaki disease. Pediatr Allergy Immunol 18:354–359
Kuo HC, Wang CL, Liang CD, Yu HR, Huang CF, Wang L et al (2009) Association of lower eosinophil-related T helper 2 (Th2) cytokines with coronary artery lesions in Kawasaki disease. Pediatr Allergy Immunol 20:266–272
Leskov KS, Klokov DY, Li J, Kinsella TJ, Boothman DA (2003) Synthesis and functional analyses of nuclear clusterin, a cell death protein. J Biol Chem 278:11590–11600
Li Y, Sagar MB, Wassler M, Shelat H, Geng YJ (2007) Apolipoprotein-J prevention of fetal cardiac myoblast apoptosis induced by ethanol. Biochem Biophys Res Commun 357:157–161
Newburger JW, Burns JC, Beiser AS, Loscalzo J (1991) Altered lipid profile after Kawasaki syndrome. Circulation 84:625–631
Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC et al (2004) Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Circulation 110:2747–2771
Nishimura S, Zaitsu M, Hara M, Yokota G, Watanabe M, Ueda Y et al (2003) A polymorphism in the promoter of the CD14 gene (CD14/-159) is associated with the development of coronary artery lesions in patients with Kawasaki disease. J Pediatr 143:357–362
Nofech-Mozes Y, Garty BZ (2003) Thrombocytopenia in Kawasaki disease: a risk factor for the development of coronary artery aneurysms. Pediatr Hematol Oncol 20:597–601
Ohno T, Igarashi H, Inoue K, Akazawa K, Joho K, Hara T (2000) Serum vascular endothelial growth factor: a new predictive indicator for the occurrence of coronary artery lesions in Kawasaki disease. Eur J Pediatr 159:424–429
Petzold A, Altintas A, Andreoni L, Bartos A, Berthele A, Blankenstein MA et al (2010) Neurofilament ELISA validation. J Immunol Methods 352:23–31
Salo E, Pesonen E, Viikari J (1991) Serum cholesterol levels during and after Kawasaki disease. J Pediatr 119:557–561
Schneider N, Weigel I, Werkmeister K, Pischetsrieder M (2010) Development and validation of an enzyme-linked immunosorbent assay (ELISA) for quantification of lysozyme in cheese. J Agric Food Chem 58:76–81
Shannan B, Seifert M, Leskov K, Willis J, Boothman D, Tilgen W et al (2006) Challenge and promise: roles for clusterin in pathogenesis, progression and therapy of cancer. Cell Death Differ 13:12–19
Shirasawa T, Miyata M, Eto H, Hamada N, Akasaki Y, Miyauchi T et al (2009) Deficiency of clusterin inhibits neointimal hyperplasia after vascular injury. J Atheroscler Thromb 16:772–781
Song D, Yeo Y, Ha K, Jang G, Lee J, Lee K et al (2009) Risk factors for Kawasaki disease-associated coronary abnormalities differ depending on age. Eur J Pediatr 168:1315–1321
Yu HR, Kuo HC, Sheen JM, Wang L, Lin IC, Wang CL et al (2009) A unique plasma proteomic profiling with imbalanced fibrinogen cascade in patients with Kawasaki disease. Pediatr Allergy Immunol 20:699–707
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This study was supported in part by NSC Grant No. 98-2314-B-182A-004-MY3 (H. R. Yu) from the National Science Council, Taiwan, and Grant No. CZRPG 880252 (K. D. Yang) from Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan.
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Yu, HR., Kuo, HC., Huang, EY. et al. Plasma Clusterin Levels in Predicting the Occurrence of Coronary Artery Lesions in Patients With Kawasaki Disease. Pediatr Cardiol 31, 1151–1156 (2010). https://doi.org/10.1007/s00246-010-9769-7
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DOI: https://doi.org/10.1007/s00246-010-9769-7