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Clinical and Diagnostic Laboratory Immunology, March 2003, p. 308-314, Vol. 10, No. 2
1071-412X/03/$08.00+0     DOI: 10.1128/CDLI.10.2.308-314.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Elevated Levels of Matrix Metalloproteinase 9 and Tissue Inhibitor of Metalloproteinase 1 during the Acute Phase of Kawasaki Disease

Pong Kian Chua,1 Marian E. Melish,2 Qigui Yu,1 Richard Yanagihara,1,2 Kara S. Yamamoto,2 and Vivek R. Nerurkar1*

Retrovirology Research Laboratory, Pacific Biomedical Research Center,1 Department of Pediatrics, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 968222

Received 29 August 2002/ Returned for modification 31 October 2002/ Accepted 30 December 2002

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.


* Corresponding author. Mailing address: Retrovirology Research Laboratory, Leahi Hospital, 3675 Kilauea Ave., Honolulu, HI 96816. Phone: (808) 732-7702. Fax: (808) 735-3682. E-mail: nerurkar{at}pbrc.hawaii.edu.


Clinical and Diagnostic Laboratory Immunology, March 2003, p. 308-314, Vol. 10, No. 2
1071-412X/03/$08.00+0     DOI: 10.1128/CDLI.10.2.308-314.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.







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