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Tight junction protein ZO-1 in Kawasaki disease
Wan-Tz Lai1,2, Hung-Chang Lee3, Ying-Hsien Huang4,5
1Department of Pediatric Gastroenterology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Insights
Lower serum zonula occludens-1 (ZO-1) levels are linked to coronary artery lesions (CAL) in Kawasaki disease (KD) patients. This finding suggests ZO-1 may be a risk factor for CAL formation in KD.
Area of Science:
- Immunology
- Gastroenterology
- Pediatrics
Background:
- Kawasaki disease (KD) is a systemic vasculitis associated with coronary artery lesions (CAL).
- Intestinal barrier integrity, maintained by tight junctions like zonula occludens-1 (ZO-1), plays a role in systemic inflammation.
- Previous studies indicate altered ZO-1 levels in asthma and cirrhosis, suggesting its involvement in inflammatory conditions.
Purpose of the Study:
- To investigate the role of tight junction zonula occludens-1 (ZO-1) in Kawasaki disease (KD).
- To assess the association between serum ZO-1 levels and treatment response to intravenous immunoglobulin (IVIG).
- To determine the correlation between serum ZO-1 levels and the development of coronary artery lesions (CAL) in KD patients.
Main Methods:
- Enrolled 40 KD patients, 12 healthy controls, and 12 febrile controls.
- Measured serum levels of tight junction ZO-1 using enzyme-linked immunosorbent assay.
- Analyzed the relationship between ZO-1 levels, IVIG treatment response, and CAL formation.
Main Results:
- Serum ZO-1 levels were lower in KD patients compared to fever controls, though not statistically significant.
- KD patients receiving a second IVIG dose showed higher serum ZO-1 levels, but this was not statistically significant.
- Significantly lower serum ZO-1 levels were observed in KD patients who developed CAL compared to those without CAL (1.89 vs. 2.39 ng/mL, p=0.027).
- Logistic regression identified lower ZO-1 levels as a risk factor for CAL formation (OR=0.235, p=0.041).
Conclusions:
- Serum tight junction ZO-1 levels are lower in Kawasaki disease patients.
- Decreased serum ZO-1 levels are associated with the formation of coronary artery lesions in KD.
- ZO-1 may serve as a potential biomarker for predicting CAL development in KD patients.
Background:
Kawasaki disease (KD) is a form of systemic febrile vasculitis that is complicated with coronary artery lesions (CAL). The tight junctions that maintain the intestinal barrier also play a role in systemic inflammatory diseases. Serum zonula occludens-1 (ZO-1) expression was found to be significantly lower in asthmatic patients, and another study reported that elevated systemic ZO-1 was positively correlated with inflammation in cirrhotic patients. A murine model of KD vasculitis demonstrated that vasculitis depended on intestinal barrier dysfunction, which is maintained by tight junctions. In this study, we aimed to investigate the role of the tight junction zonula occludens-1 (ZO-1) in the treatment response of intravenous immunoglobulin (IVIG) and the occurrence of CAL formation in KD patients.
Methods:
We enrolled 40 KD patients, 12 healthy controls, and 12 febrile controls in this study. The serum levels of tight junction ZO-1 were determined by enzyme-linked immunosorbent assay.
Results:
The serum ZO-1 level was higher in the fever control group but did not reach a statistical significance. KD patients who received a second dose of IVIG treatment due to initial IVIG unresponsiveness had a higher serum levels of tight junction ZO-1, but without statistical significance (2.15 ± 0.18 vs. 2.69 ± 0.31 ng/mL, p = 0.058). KD patients who developed a CAL demonstrated a significant lower serum tight junction ZO-1 levels than KD without CAL formation (1.89 ± 0.16 vs. 2.39 ± 0.15 ng/mL, p = 0.027). After multiple logistic regression analysis, ZO-1 levels [(95% confidence interval (CI): 0.058 ~ 0.941, odds ratio (OR) = 0.235, p = 0.041)] showed as the risk factor for CAL formation.
Conclusion:
Serum levels of tight junction ZO-1 levels were lower in KD patients than fever controls and associated with CAL formation.
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