Pathogenesis of Kawasaki Disease: Elevated Plasma Levels of Matrix Metalloproteinase 9


            Kawasaki disease (KD) is an acute self-limited multi-system vasculitis of unknown etiology affecting infants and young children.  Unless treated with high-dose intravenous gamma globulin and aspirin, patients frequently develop coronary aneurysms.  Matrix metalloproteinases (MMP) are a class of zinc-dependent, calcium-requiring enzymes capable of degrading extracellular matrices.  MMP-9, which is secreted complexed to tissue inhibitor of metalloproteinase 1 (TIMP-1), has been implicated in the pathological conditions of abdominal aortic aneurysm formation.  Since the clinical and pathological features of KD include inflammation and weakening of blood vessels, we investigated MMP-9 and TIMP-1 enzyme and/or protein levels in KD patients and non-KD febrile controls.  Archival and fresh acute- and convalescent-phase paired plasma or serum samples from 27 KD patients (11 females, 16 males) and 13 non-KD febrile patients (7 females, 6 males) were analyzed for MMP-9 enzyme activity by gelatin zymography.  MMP-9 and TIMP-1 protein levels were measured using enzyme-linked immunosorbent assays.  Statistical analysis was performed using the Studentās t-test and linear regression.  Markedly elevated MMP-9 enzymatic activity and protein levels, as well as TIMP-1 protein levels, were found in the acute stage of KD compared to the convalescent phase and non-KD febrile patients.  The significantly elevated MMP-9 enzyme and protein levels during the acute phase of KD may reflect vascular remodeling or an inflammatory response to a microbial agent (Figures 2 and 3).  Further studies of MMP-9 and other molecules important in vascular damage and repair may elucidate important factors in the pathogenesis of KD.  Furthermore, the elevated TIMP-1 protein levels, together with MMP-9, could be useful as a much-needed diagnostic marker.

Chua, P.K., Yu, Q., Nerurkar, V.R., Yamamoto, K.S., Melish, M.E., and Yanagihara, R.:  Elevated plasma levels of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 during the acute phase of Kawasaki syndrome: potential use as a diagnostic marker.  Pediatric Research 1999 (in preparation).

Yu, Q., Chua, P.K., Melish, M.E., and Yanagihara, R.:  Matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 levels in peripheral blood mononuclear cells in Kawasaki syndrome.  Journal of Pediatrics 1999 (in preparation).

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