Introduction:
Kawasaki disease (KD) patients who are resistant to intravenous immunoglobulins (IVIG) are at increased risk of developing aneurysms, but to date there are no biomarkers that identify them. Calprotectin is a protein that is involved in the immune and inflammatory response. The objective of KAWACALP Study is to assess if serum calprotectin (CPS) can be used as a predictor to identify aneurysms before they form in KD.
Methods:
A multicentre, national, observational, cohort study was conducted prospectively between September 2018 and February 2023. CPS was analysed at four points in the evolution of KD in 74 patients from four Spanish hospitals. The CPS and other clinical and analytical values were compared between patients with complete/incomplete KD, patients with sensitive/resistant KD, and patients with or without aneurysms.
Results:
In resistant patients, unlike sensitive ones, CPS levels after treatment (CPS-2) remained elevated and can predict unresponsiveness to IVIG (OR=1.12 [95% CI 1.02; 1.23]; 0.018). For CPS-2 value ≥ 14.09 μg/mL, sensitivity: 75%, specificity: 72.97%, AUC ROC: 0.75 (95% CI: 0.50; 1.00).
In patients with aneurysms, CPS levels before treatment (CPS-1) were higher than in patients without coronary involvement, and did not decrease significantly after treatment. CPS-1 and CPS-2 values enabled the prediction of patients at risk of aneurysms (CPS-1 OR= 1.09 [95% CI 1.01; 1.18]; 0.029), (CPS-2 OR= 1.11 [95% CI 1.01; 1,22]; 0.03). For CPS-1 value ≥ 21.49 μg/ml, sensitivity for detecting aneurysms: 100%, specificity: 71.05%, AUC ROC: 0.86 (95% CI: 0.75, 0.98).
Discussion:
In patients with Kawasaki disease who developed coronary aneurysms, serum calprotectin was significantly higher at the time of diagnosis and remained elevated after treatment with IGIV, unlike patients without coronary disease. Calprotectin level at the time of diagnosis ≥ 21.49 μg/ml, has a sensitivity of 100% to detect aneurysms. Patients who were refractory to treatment also did not experience a significant decrease in serum calprotectin after therapy; this was not observed in sensitive patients. We believe that serum calprotectin can be used as a prognostic biomarker in patients with Kawasaki disease, for the early detection of those patients with a higher probability of aneurysm occurrence.