Kawasaki disease (KD) is an acute, self-limiting, multisystem
vasculitis of unknown etiology affecting infants and young children. Unless treated promptly with high-dose intravenous
gamma globulin and
aspirin, patients frequently develop
coronary aneurysms. Previously,
matrix metalloproteinase 9 (MMP-9), which is secreted complexed to
tissue inhibitor of metalloproteinase 1 (TIMP-1), has been implicated in
abdominal aortic aneurysm formation. Since the clinical and pathological features of KD include
inflammation and weakening of blood vessels, we analyzed acute- and convalescent-phase paired plasma or serum samples from 31 KD patients, 7 patients who did not completely meet the criteria for KD, and 26 non-KD controls (9 febrile and 17 afebrile patients) for pro-MMP-9 (92 kDa)
enzyme activity by
gelatin zymography and for active MMP-9 (83 kDa), pro-MMP-9, and
TIMP-1 protein levels by
enzyme-linked
immunosorbent assay. Statistical analysis was performed by using Student t tests, linear regression, and the Wilcoxon rank-sum test. Markedly elevated pro-MMP-9 enzymatic activity, pro-MMP-9
protein levels, and
TIMP-1 protein levels were found during the acute phase of illness in patients with clinically established KD and in patients who were suspected of having KD but did not meet all of the criteria. There was no significant difference in active MMP-9 levels. Furthermore, pro-MMP-9 and
TIMP-1 protein levels were significantly elevated among KD patients, compared to those of febrile and afebrile non-KD controls. The significantly elevated pro-MMP-9
enzyme and
protein levels during the acute phase of KD may reflect
vascular remodeling or an inflammatory response to a microbial agent, suggesting a pathophysiological role for MMP-9 in
coronary aneurysm formation.