Children with Kawasaki disease exhibit persistent oxidative stress during follow-up, as evidenced by increased neutrophil ROS production, indicating ongoing cellular oxidative activity, and elevated ROS may serve as an accessible biomarker for coronary artery abnormalities and long-term cardiovascular risk.
Key Findings
Results
Neutrophil ROS production was increased in KD patients during follow-up, with a significant rise observed in the intermediate follow-up group compared to healthy controls.
Neutrophil ROS production (ΔMFI) was significantly elevated in Group 2 (>1.5–3 years post-diagnosis) compared with healthy controls (p = 0.03).
ROS was assessed using a dihydrorhodamine-123 flow cytometric assay.
62 children with KD and 20 age- and gender-matched healthy controls were enrolled.
The finding suggests persistent cellular oxidative activity beyond the acute phase of Kawasaki disease.
Results
Serum nitrite levels were comparable across all three KD follow-up groups and healthy controls.
Serum nitrite levels were: Group 1: 3.46 ± 1.64; Group 2: 5.04 ± 2.55; Group 3: 5.22 ± 3.00; HC: 3.33 ± 1.98.
The difference across groups was not statistically significant (p = 0.06).
KD patients were stratified into three groups based on time since diagnosis.
Results
Serum nitrate levels were comparable across all three KD follow-up groups and healthy controls.
Serum nitrate levels were: Group 1: 63.07 ± 41.32; Group 2: 58.63 ± 27.12; Group 3: 64.57 ± 26.36; HC: 57.49 ± 8.68.
The difference across groups was not statistically significant (p = 0.43).
Serum nitrite and nitrate were measured as indicators of extracellular nitric oxide metabolism.
Results
Serum nitrate and nitrite levels did not differ significantly between KD patients with and without coronary artery abnormalities across all follow-up groups.
Nitrate comparisons between CAA and non-CAA subgroups: Group 1 p = 0.60; Group 2 p > 0.99; Group 3 p = 0.10.
Nitrite comparisons between CAA and non-CAA subgroups: Group 1 p > 0.99; Group 2 p > 0.99; Group 3 p = 0.90.
Subgroup analysis was performed within each time-stratified group separately.
Results
No significant correlations were found between oxidative stress markers and systemic inflammatory parameters in KD patients on follow-up.
Neither serum nitrite, nitrate, nor neutrophil ROS production correlated significantly with systemic inflammatory parameters.
This finding suggests that oxidative stress persists independently of systemic inflammation during long-term KD follow-up.
The study was a prospective, single-centre study conducted in a developing country context where such data are limited.
Conclusions
Elevated neutrophil ROS production was proposed as a potentially accessible biomarker for coronary artery abnormalities and long-term cardiovascular risk in KD patients on follow-up.
The authors conclude that 'elevated ROS may serve as an accessible biomarker for CAAs and long-term cardiovascular risk in KD patients on follow-up.'
ROS was detectable using flow cytometric dihydrorhodamine-123 assay, which the authors suggest is accessible for clinical use.
The association between persistent ROS elevation and CAAs supports ongoing vascular surveillance in KD follow-up.
What This Means
Kawasaki disease (KD) is an inflammatory condition that primarily affects young children and can cause lasting damage to the coronary arteries — the blood vessels that supply the heart. Even after the acute illness resolves, children with KD may remain at elevated cardiovascular risk. This research suggests that a specific marker of cellular stress called reactive oxygen species (ROS), produced by immune cells called neutrophils, remains elevated in children with KD years after their initial diagnosis. In particular, children who were between 1.5 and 3 years past their diagnosis showed significantly higher neutrophil ROS levels compared to healthy children of similar age and sex.
Interestingly, other markers of oxidative stress — specifically nitrite and nitrate levels in the blood, which reflect how the body processes nitric oxide — were not significantly different between KD patients and healthy controls, nor between KD patients who had developed coronary artery abnormalities and those who had not. This suggests that different pathways of oxidative stress may behave differently over the course of the disease, and that neutrophil ROS may be more sensitive to persistent vascular changes than nitric oxide metabolites.
This research suggests that measuring neutrophil ROS production using a standard laboratory test (flow cytometry) could be a useful and accessible way to monitor ongoing cardiovascular risk in children recovering from KD, particularly in settings where more advanced imaging or biomarker tests may not be available. The finding that oxidative stress persists independently of general inflammatory markers also implies that routine inflammation tests may not be sufficient to capture all aspects of long-term risk in these patients. Larger studies will be needed to confirm these findings and determine whether ROS measurements should be incorporated into standard follow-up care for KD.
Kumrah R, Goyal T, Singhal M, Bhatia P, Pandiarajan V, Jindal A, et al.. (2026). Association of persistent oxidative stress markers with coronary artery abnormalities in Kawasaki disease patients on follow-up.. Pediatric rheumatology online journal. https://doi.org/10.1186/s12969-026-01249-w