Abstract O.31: Tenascin-C can be a Novel Prognostic Biomarker For Kawasaki Disease

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Abstract

Tenascin-C (TNC) is an extracellular matrix glycoprotein sparsely detected in normal but highly expressed in pathological condition associated with inflammation in variety of tissues. By taking advantage of its specific expression, TNC is applicable as a biomarker and a molecular imaging target for diagnosis of disease activity for ventricular remodeling. In blood vessels, the expression of TNC in normal is generally low but strong expression is linked with several pathological conditions such as pulmonary artery hypertension, coronary atherosclerotic intima, and aortic aneurysm/ dissection. We hypothesized that TNC could be useful for evaluating disease activity of Kawasaki Disease(KD). We measured serum level of TNC of 174 patients with KD using ELSA and found that the TNC level was significantly higher than that of the controls, and the initial treatment with intravenous immunoglobulin decreased the level. Combination of serum TNC and Kobayashi score increased the accuracy to identify cases at a high risk of unresponsiveness to high-dose intravenous immunoglobulin. Immunohistochemical analysis of autopsied cases showed that TNC was strongly expressed in coronary vascular lesion at acute stage of KD patients as well as in the Candida albicans-induced murine model of vasculitis/aneurysm. Biomechanical analysis demonstrated that vascular flexibility was reduced in TNC knockout mice. A combination of inflammation and mechanical stress to aorta induced dissecting aneurysm in TNC knockout mice. In vitro, TNC enhanced macrophage migration and cytokine synthesis, meanwhile TNC synthesis was up-regulated by various pro-inflammatory cytokines. These results suggest that TNC is expressed in vascular lesion of KD reflecting active inflammation, which has diverse functions to modulate not only inflammatory response but also regulate vascular remodeling and aneurysm formation. TNC could be a key molecule in pathophysiology and a promising biomarker of KD.

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